1) Lung cancer tumors display a high number of somatic mutations, rendering them more immunogenic. The presence of tumor-infiltrating FOXP3+ regulatory T-cells is associated with recurrence in early-stage non-small cell lung cancer patients.
2) Brambilla et al. (2016) found that lymphocyte infiltration has a prognostic effect in resectable non-small cell lung cancer.
3) Immunotherapies targeting CTLA-4 and PD-1/PD-L1 have shown efficacy in lung cancer treatment, with nivolumab demonstrating improved overall survival compared to docetaxel in previously treated squamous and non-squamous non-small cell lung cancer
1) The document discusses tumor immunology and mechanisms of tumor immune evasion. It describes how tumors can downregulate MHC expression, secrete immunosuppressive factors, inhibit T cell function through checkpoint pathways like PD-1/PD-L1, and recruit immunosuppressive cells like Tregs.
2) Checkpoint pathways like CTLA-4 and PD-1 normally regulate T cell activation, but tumors can exploit these pathways to evade immune destruction by overexpressing ligands that bind these inhibitory receptors.
3) Several immunotherapies targeting CTLA-4 and PD-1/PD-L1 have been developed including ipilimumab, nivolumab, pembrol
1) Recent immunotherapy advances for advanced NSCLC include the approval of pembrolizumab as a first-line treatment for patients with PD-L1 expression ≥50% based on results from the KEYNOTE-024 trial showing improved progression-free and overall survival compared to chemotherapy.
2) The Phase III KEYNOTE-407 trial found that combining pembrolizumab with chemotherapy improved progression-free survival compared to chemotherapy alone in patients with untreated metastatic squamous NSCLC, regardless of PD-L1 expression level.
3) Combining chemotherapy with immunotherapy may enhance the immune response by increasing antigen presentation, disrupting immune evasion mechanisms, and improving outcomes compared to chemotherapy or immunotherapy alone.
Jessica Donington, MD, Natasha Leighl, MD, MMSc, FRCPC, FASCO, and Brendon Stiles, MD, prepared useful practice aids pertaining to the role of immunotherapy in lung cancer for this CME/MOC/CNE activity titled, "The Expanding Role of Immunotherapy in Locally Advanced and Earlier Stages of Lung Cancer: Rationale, Current Evidence, Key Trials, and Implications for Thoracic Surgeons." For the full presentation, monograph, complete CME/MOC/CNE information, and to apply for credit, please visit us at http://bit.ly/2WibbtU. CME/MOC/CNE credit will be available until June 16, 2020.
2015 04 Tratamiento del NSCLC basado en alteraciones molecularesMartín Lázaro
1) The document discusses biomarker-guided treatment selection for non-small cell lung cancer (NSCLC) and summarizes data from several clinical trials evaluating targeted therapies versus chemotherapy in patients with activating EGFR mutations.
2) The IPASS trial showed that gefitinib resulted in significantly longer progression-free survival compared to carboplatin/paclitaxel in patients with EGFR mutation-positive NSCLC.
3) The EURTAC trial found that erlotinib doubled progression-free survival compared to chemotherapy as first-line treatment for patients with EGFR mutation-positive NSCLC.
1) EGFR mutations are found in 10-30% of NSCLC cases and are associated with response to EGFR TKIs as first-line treatment.
2) Several studies including IPASS, EURTAC and LUX-Lung 3 have shown superior PFS for first-generation EGFR TKIs like gefitinib and erlotinib and the second-generation TKI afatinib compared to platinum-based chemotherapy as first-line treatment for EGFR mutation-positive NSCLC.
3) Meta-analyses of these studies demonstrate improved PFS for EGFR TKIs compared to chemotherapy in EGFR mutation-positive NSCLC, though OS is generally similar between the treatments
Roy H. Decker, MD, PhD; Kristin Higgins, MD; and Jyoti D. Patel, MD, prepared useful practice aids pertaining to immunotherapies in lung cancer for this CME/MOC activity titled “NSCLC Tumor Board: Navigating the Evolving Role of Immunotherapy in Multimodal Management of Locally Advanced and Early-Stage Lung Cancer.” For the full presentation, monograph, complete CME/MOC information, and to apply for credit, please visit us at http://bit.ly/2mFfEWE. CME/MOC credit will be available until October 22, 2020.
1) The document discusses tumor immunology and mechanisms of tumor immune evasion. It describes how tumors can downregulate MHC expression, secrete immunosuppressive factors, inhibit T cell function through checkpoint pathways like PD-1/PD-L1, and recruit immunosuppressive cells like Tregs.
2) Checkpoint pathways like CTLA-4 and PD-1 normally regulate T cell activation, but tumors can exploit these pathways to evade immune destruction by overexpressing ligands that bind these inhibitory receptors.
3) Several immunotherapies targeting CTLA-4 and PD-1/PD-L1 have been developed including ipilimumab, nivolumab, pembrol
1) Recent immunotherapy advances for advanced NSCLC include the approval of pembrolizumab as a first-line treatment for patients with PD-L1 expression ≥50% based on results from the KEYNOTE-024 trial showing improved progression-free and overall survival compared to chemotherapy.
2) The Phase III KEYNOTE-407 trial found that combining pembrolizumab with chemotherapy improved progression-free survival compared to chemotherapy alone in patients with untreated metastatic squamous NSCLC, regardless of PD-L1 expression level.
3) Combining chemotherapy with immunotherapy may enhance the immune response by increasing antigen presentation, disrupting immune evasion mechanisms, and improving outcomes compared to chemotherapy or immunotherapy alone.
Jessica Donington, MD, Natasha Leighl, MD, MMSc, FRCPC, FASCO, and Brendon Stiles, MD, prepared useful practice aids pertaining to the role of immunotherapy in lung cancer for this CME/MOC/CNE activity titled, "The Expanding Role of Immunotherapy in Locally Advanced and Earlier Stages of Lung Cancer: Rationale, Current Evidence, Key Trials, and Implications for Thoracic Surgeons." For the full presentation, monograph, complete CME/MOC/CNE information, and to apply for credit, please visit us at http://bit.ly/2WibbtU. CME/MOC/CNE credit will be available until June 16, 2020.
2015 04 Tratamiento del NSCLC basado en alteraciones molecularesMartín Lázaro
1) The document discusses biomarker-guided treatment selection for non-small cell lung cancer (NSCLC) and summarizes data from several clinical trials evaluating targeted therapies versus chemotherapy in patients with activating EGFR mutations.
2) The IPASS trial showed that gefitinib resulted in significantly longer progression-free survival compared to carboplatin/paclitaxel in patients with EGFR mutation-positive NSCLC.
3) The EURTAC trial found that erlotinib doubled progression-free survival compared to chemotherapy as first-line treatment for patients with EGFR mutation-positive NSCLC.
1) EGFR mutations are found in 10-30% of NSCLC cases and are associated with response to EGFR TKIs as first-line treatment.
2) Several studies including IPASS, EURTAC and LUX-Lung 3 have shown superior PFS for first-generation EGFR TKIs like gefitinib and erlotinib and the second-generation TKI afatinib compared to platinum-based chemotherapy as first-line treatment for EGFR mutation-positive NSCLC.
3) Meta-analyses of these studies demonstrate improved PFS for EGFR TKIs compared to chemotherapy in EGFR mutation-positive NSCLC, though OS is generally similar between the treatments
Roy H. Decker, MD, PhD; Kristin Higgins, MD; and Jyoti D. Patel, MD, prepared useful practice aids pertaining to immunotherapies in lung cancer for this CME/MOC activity titled “NSCLC Tumor Board: Navigating the Evolving Role of Immunotherapy in Multimodal Management of Locally Advanced and Early-Stage Lung Cancer.” For the full presentation, monograph, complete CME/MOC information, and to apply for credit, please visit us at http://bit.ly/2mFfEWE. CME/MOC credit will be available until October 22, 2020.
The document summarizes a presentation on using gene profiling and biomarkers to better classify and treat non-small cell lung cancer (NSCLC). It discusses current and emerging markers like EGFR mutations, ALK translocations, and FGFR1 amplifications that define NSCLC subtypes and can guide targeted therapies. Integrating multiple genomic analyses may help characterize unknown abnormalities in a third of NSCLC tumors and identify new treatment opportunities.
Role of Chemotherapy, Targeted therapy and Immunotherapy in NSCLC (Part II)Mohammed Fathy
1) The document discusses targeted therapies for non-small cell lung cancer (NSCLC) with ALK translocations, including crizotinib, alectinib, brigatinib, ceritinib, and lorlatinib.
2) Alectinib is now considered the preferred first-line treatment for ALK-positive NSCLC based on Phase III trials showing it is more effective than crizotinib.
3) For patients who progress on a first-generation ALK inhibitor like crizotinib, later-generation ALK inhibitors such as ceritinib, brigatinib, and lorlatinib have demonstrated efficacy in clinical trials as subsequent therapies.
The document discusses lung cancer subtypes and molecular features that can guide treatment. It provides statistics on the distribution of histology types among lung cancer cases. It also summarizes several key studies investigating targeted therapies such as EGFR TKIs versus chemotherapy as first-line treatment for advanced non-small cell lung cancer, noting improved progression-free survival with TKIs in patients with EGFR mutations. Molecular testing is increasingly important for determining personalized treatment approaches in lung cancer.
Role of Chemotherapy, Targeted therapy and Immunotherapy in NSCLC Part IMohammed Fathy
1) Chemotherapy provides a modest survival benefit for early stage NSCLC based on multiple randomized trials. The absolute improvement in 5-year survival is approximately 5%.
2) The IALT trial showed a 4% improvement in 5-year survival with cisplatin-based chemotherapy compared to observation alone for stage I-III NSCLC.
3) The JBR.10 trial demonstrated an 11% absolute improvement in 5-year survival with vinorelbine and cisplatin compared to observation for stage IB-II NSCLC. However, the benefit was largely seen in stage II patients.
Treatment of Non–Small-Cell Lung Cancer with Erlotinib or Gefitinibseayat1103
This document discusses a clinical trial comparing the efficacy of erlotinib and gefitinib for the treatment of non-small cell lung cancer. The trial found that both erlotinib and gefitinib showed efficacy in NSCLC patients with EGFR mutations, with erlotinib demonstrating a median progression-free survival of 10.8 months compared to 5.4 months for standard chemotherapy in EGFR mutation-positive patients. Subsequent studies confirmed the superior efficacy of both erlotinib and gefitinib in NSCLC patients with EGFR mutations, particularly those with exon 19 deletions or L858R mutations. The document concludes by discussing the current NCCN guidelines for use of erlotinib and
The document summarizes key information from a conference on gene profiling in clinical oncology, including:
1) New markers such as EGFR, KRAS, ALK, HER2, and PI3K mutations are defining subsets of non-small cell lung cancer and informing targeted therapy approaches.
2) Drugs like erlotinib, gefitinib, and crizotinib, which target EGFR, ALK, and c-MET mutations respectively, have shown efficacy in molecularly selected patient populations.
3) Comprehensive genomic profiling of lung tumors is needed to discover new targets, as around a third of cases still have unknown driver mutations.
Acquired Resistance to Targeted Therapy in EGFR and ALK-Positive Lung Cancer:...H. Jack West
This is a presentation I did for a meeting on new general management of acquired resistance in 2014, including the concept of local therapy for limited progression, and new treatment approaches and new agents for this setting. It features discussion of several of the most important trials.
Best of ASCO Metastatic Non-Small Cell Lung CancerH. Jack West
Dr. Jack West's presentation on highlights in advanced non-small cell lung cancer from ASCO 2014, focusing on new agents ramucirumab and necitumumab for broad NSCLC populations, crizotinib and ceritinib for ALK-positive NSCLC, EGFR inhibitor-options of afatinib and bevacizumab added to erlotinib for first line treatment of EGFR mutation-positive NSCLC, and AZD9291 or CO1686 for EGFR mutation-positive patients with acquired resistance.
This document discusses lung cancer incidence, mortality, histology, molecular drivers, and first-line treatment approaches for advanced non-small cell lung cancer (NSCLC). It provides statistics showing lung cancer is a leading cause of cancer death and NSCLC subtypes include adenocarcinoma, squamous cell carcinoma, and large cell carcinoma. Mutations in genes like EGFR, KRAS, ALK, and ROS1 can predict response to targeted therapies. For first-line treatment of advanced NSCLC, patients may receive a platinum-based doublet chemotherapy, or an EGFR or ALK tyrosine kinase inhibitor depending on mutation status and other factors. Clinical trials demonstrate superior outcomes with EGFR tyrosine kinase inhibitors compared to
Recent advances in targeted therapy for metastatic lung cancerAlok Gupta
This document discusses recent advances in targeted therapy for metastatic lung cancer. It summarizes key findings from several clinical trials evaluating third-generation EGFR TKIs like osimertinib for patients with EGFR mutation-positive NSCLC. The document highlights that osimertinib provides significantly longer progression-free survival compared to earlier generation EGFR TKIs, with a median PFS of 18.9 months versus 10.2 months. Osimertinib also demonstrated a higher objective response rate and longer duration of response. Benefits were consistent across patient subgroups.
This document discusses evolving strategies for the personalized treatment of non-small cell lung cancer (NSCLC). It covers histological and molecular subtypes of NSCLC, key clinical trials of the EGFR tyrosine kinase inhibitor gefitinib, mechanisms of acquired resistance to EGFR TKIs, and approaches to managing resistance. A phase IV study showed gefitinib was effective first-line therapy for Caucasian patients with EGFR mutation-positive NSCLC, with a 69.8% response rate and favorable progression-free and overall survival. Exploratory analyses found plasma samples could accurately assess EGFR mutation status when tumor tissue was unavailable. The document reviews strategies for treating systemic and central nervous system progression after acquiring resistance to EGFR T
10 Key ASCO 2014 Presentations in Lung CancerH. Jack West
Dr. Jack West offers a list of 10 of the most important, timely abstract presentations in lung cancer, both non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC), at the annual ASCO 2014 conference.
The document summarizes key information about prostate cancer including incidence, mortality rates, clinical stages, risk groups for localized prostate cancer, treatment options for advanced disease including hormone therapy and chemotherapy, and results from clinical trials of chemotherapy agents like docetaxel and cabazitaxel.
The document discusses renal cancer (kidney cancer) and advances in its treatment. It describes several targeted drugs that have improved outcomes for metastatic renal cell carcinoma (mRCC) compared to previous immunotherapy options. Drugs include tyrosine kinase inhibitors like sunitinib, sorafenib, pazopanib and axitinib as well as the mTOR inhibitor temsirolimus. Clinical trials have established these as standard first and second line options depending on a patient's risk level and prior treatment history. Ongoing research focuses on optimizing treatment sequencing and identifying biomarkers to guide more personalized therapy selection.
Estado actual de terapia sistémica en cáncer renal metastásicoMauricio Lema
This document discusses the current management of metastatic renal cell carcinoma (mRCC). It provides an overview of targeted therapies for mRCC including tyrosine kinase inhibitors (TKIs) such as sunitinib, pazopanib, and cabozantinib that target the VEGF pathway. Clinical trial results are presented comparing TKIs in first-line mRCC. Active surveillance is also discussed as a treatment option for select asymptomatic or minimally symptomatic mRCC patients. Toxicities of TKIs like fatigue, diarrhea and hand-foot syndrome are reviewed along with their negative impact on quality of life.
Estudio Paramount cáncer de pulmón 2014Martín Lázaro
1) The PARAMOUNT study evaluated pemetrexed maintenance therapy after induction with pemetrexed/cisplatin doublet chemotherapy in patients with advanced non-squamous non-small cell lung cancer (NSCLC).
2) The study met its primary endpoint, finding that pemetrexed maintenance significantly reduced the risk of disease progression compared to placebo (HR=0.62, p<0.0001).
3) Updated results showed pemetrexed maintenance also significantly improved overall survival compared to placebo, with median OS of 13.9 months vs 11 months (HR=0.78, p=0.0199).
Role of molecular targeted therapy in HCC DubaiPAIRS WEB
This document discusses hepatocellular carcinoma (HCC) and approaches to treating this growing clinical challenge. It provides background on HCC pathogenesis and prognostic factors such as tumor stage, liver function, and tumor biology. Treatment options including curative therapies for early stage disease and palliative options for advanced HCC are described. The role of the targeted therapy sorafenib in treating advanced HCC is summarized based on results from Phase III trials showing it can prolong both overall survival and time to progression compared to placebo. Ongoing research into additional targeted agents and combination approaches for HCC are also mentioned.
El documento describe los resultados del estudio COU-AA-302 sobre el uso de abiraterona más prednisona versus placebo más prednisona en pacientes con cáncer de próstata resistente a la castración y sin quimioterapia previa. El estudio encontró que la abiraterona aumentó significativamente la supervivencia global y el tiempo libre de progresión radiográfica en comparación con el placebo.
Este documento describe la inmunoterapia en el cáncer. Explica que hay 12.7 millones de nuevos casos de cáncer cada año y 7.6 millones de muertes, y que la incidencia y mortalidad están aumentando en países en desarrollo. La inmunoterapia es una parte central del tratamiento del cáncer y manipula el sistema inmune para activar la inmunidad antitumoral. Existen varias clases de tratamiento como quimioterapia, terapia hormonal e inmunoterapia.
The document summarizes a presentation on using gene profiling and biomarkers to better classify and treat non-small cell lung cancer (NSCLC). It discusses current and emerging markers like EGFR mutations, ALK translocations, and FGFR1 amplifications that define NSCLC subtypes and can guide targeted therapies. Integrating multiple genomic analyses may help characterize unknown abnormalities in a third of NSCLC tumors and identify new treatment opportunities.
Role of Chemotherapy, Targeted therapy and Immunotherapy in NSCLC (Part II)Mohammed Fathy
1) The document discusses targeted therapies for non-small cell lung cancer (NSCLC) with ALK translocations, including crizotinib, alectinib, brigatinib, ceritinib, and lorlatinib.
2) Alectinib is now considered the preferred first-line treatment for ALK-positive NSCLC based on Phase III trials showing it is more effective than crizotinib.
3) For patients who progress on a first-generation ALK inhibitor like crizotinib, later-generation ALK inhibitors such as ceritinib, brigatinib, and lorlatinib have demonstrated efficacy in clinical trials as subsequent therapies.
The document discusses lung cancer subtypes and molecular features that can guide treatment. It provides statistics on the distribution of histology types among lung cancer cases. It also summarizes several key studies investigating targeted therapies such as EGFR TKIs versus chemotherapy as first-line treatment for advanced non-small cell lung cancer, noting improved progression-free survival with TKIs in patients with EGFR mutations. Molecular testing is increasingly important for determining personalized treatment approaches in lung cancer.
Role of Chemotherapy, Targeted therapy and Immunotherapy in NSCLC Part IMohammed Fathy
1) Chemotherapy provides a modest survival benefit for early stage NSCLC based on multiple randomized trials. The absolute improvement in 5-year survival is approximately 5%.
2) The IALT trial showed a 4% improvement in 5-year survival with cisplatin-based chemotherapy compared to observation alone for stage I-III NSCLC.
3) The JBR.10 trial demonstrated an 11% absolute improvement in 5-year survival with vinorelbine and cisplatin compared to observation for stage IB-II NSCLC. However, the benefit was largely seen in stage II patients.
Treatment of Non–Small-Cell Lung Cancer with Erlotinib or Gefitinibseayat1103
This document discusses a clinical trial comparing the efficacy of erlotinib and gefitinib for the treatment of non-small cell lung cancer. The trial found that both erlotinib and gefitinib showed efficacy in NSCLC patients with EGFR mutations, with erlotinib demonstrating a median progression-free survival of 10.8 months compared to 5.4 months for standard chemotherapy in EGFR mutation-positive patients. Subsequent studies confirmed the superior efficacy of both erlotinib and gefitinib in NSCLC patients with EGFR mutations, particularly those with exon 19 deletions or L858R mutations. The document concludes by discussing the current NCCN guidelines for use of erlotinib and
The document summarizes key information from a conference on gene profiling in clinical oncology, including:
1) New markers such as EGFR, KRAS, ALK, HER2, and PI3K mutations are defining subsets of non-small cell lung cancer and informing targeted therapy approaches.
2) Drugs like erlotinib, gefitinib, and crizotinib, which target EGFR, ALK, and c-MET mutations respectively, have shown efficacy in molecularly selected patient populations.
3) Comprehensive genomic profiling of lung tumors is needed to discover new targets, as around a third of cases still have unknown driver mutations.
Acquired Resistance to Targeted Therapy in EGFR and ALK-Positive Lung Cancer:...H. Jack West
This is a presentation I did for a meeting on new general management of acquired resistance in 2014, including the concept of local therapy for limited progression, and new treatment approaches and new agents for this setting. It features discussion of several of the most important trials.
Best of ASCO Metastatic Non-Small Cell Lung CancerH. Jack West
Dr. Jack West's presentation on highlights in advanced non-small cell lung cancer from ASCO 2014, focusing on new agents ramucirumab and necitumumab for broad NSCLC populations, crizotinib and ceritinib for ALK-positive NSCLC, EGFR inhibitor-options of afatinib and bevacizumab added to erlotinib for first line treatment of EGFR mutation-positive NSCLC, and AZD9291 or CO1686 for EGFR mutation-positive patients with acquired resistance.
This document discusses lung cancer incidence, mortality, histology, molecular drivers, and first-line treatment approaches for advanced non-small cell lung cancer (NSCLC). It provides statistics showing lung cancer is a leading cause of cancer death and NSCLC subtypes include adenocarcinoma, squamous cell carcinoma, and large cell carcinoma. Mutations in genes like EGFR, KRAS, ALK, and ROS1 can predict response to targeted therapies. For first-line treatment of advanced NSCLC, patients may receive a platinum-based doublet chemotherapy, or an EGFR or ALK tyrosine kinase inhibitor depending on mutation status and other factors. Clinical trials demonstrate superior outcomes with EGFR tyrosine kinase inhibitors compared to
Recent advances in targeted therapy for metastatic lung cancerAlok Gupta
This document discusses recent advances in targeted therapy for metastatic lung cancer. It summarizes key findings from several clinical trials evaluating third-generation EGFR TKIs like osimertinib for patients with EGFR mutation-positive NSCLC. The document highlights that osimertinib provides significantly longer progression-free survival compared to earlier generation EGFR TKIs, with a median PFS of 18.9 months versus 10.2 months. Osimertinib also demonstrated a higher objective response rate and longer duration of response. Benefits were consistent across patient subgroups.
This document discusses evolving strategies for the personalized treatment of non-small cell lung cancer (NSCLC). It covers histological and molecular subtypes of NSCLC, key clinical trials of the EGFR tyrosine kinase inhibitor gefitinib, mechanisms of acquired resistance to EGFR TKIs, and approaches to managing resistance. A phase IV study showed gefitinib was effective first-line therapy for Caucasian patients with EGFR mutation-positive NSCLC, with a 69.8% response rate and favorable progression-free and overall survival. Exploratory analyses found plasma samples could accurately assess EGFR mutation status when tumor tissue was unavailable. The document reviews strategies for treating systemic and central nervous system progression after acquiring resistance to EGFR T
10 Key ASCO 2014 Presentations in Lung CancerH. Jack West
Dr. Jack West offers a list of 10 of the most important, timely abstract presentations in lung cancer, both non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC), at the annual ASCO 2014 conference.
The document summarizes key information about prostate cancer including incidence, mortality rates, clinical stages, risk groups for localized prostate cancer, treatment options for advanced disease including hormone therapy and chemotherapy, and results from clinical trials of chemotherapy agents like docetaxel and cabazitaxel.
The document discusses renal cancer (kidney cancer) and advances in its treatment. It describes several targeted drugs that have improved outcomes for metastatic renal cell carcinoma (mRCC) compared to previous immunotherapy options. Drugs include tyrosine kinase inhibitors like sunitinib, sorafenib, pazopanib and axitinib as well as the mTOR inhibitor temsirolimus. Clinical trials have established these as standard first and second line options depending on a patient's risk level and prior treatment history. Ongoing research focuses on optimizing treatment sequencing and identifying biomarkers to guide more personalized therapy selection.
Estado actual de terapia sistémica en cáncer renal metastásicoMauricio Lema
This document discusses the current management of metastatic renal cell carcinoma (mRCC). It provides an overview of targeted therapies for mRCC including tyrosine kinase inhibitors (TKIs) such as sunitinib, pazopanib, and cabozantinib that target the VEGF pathway. Clinical trial results are presented comparing TKIs in first-line mRCC. Active surveillance is also discussed as a treatment option for select asymptomatic or minimally symptomatic mRCC patients. Toxicities of TKIs like fatigue, diarrhea and hand-foot syndrome are reviewed along with their negative impact on quality of life.
Estudio Paramount cáncer de pulmón 2014Martín Lázaro
1) The PARAMOUNT study evaluated pemetrexed maintenance therapy after induction with pemetrexed/cisplatin doublet chemotherapy in patients with advanced non-squamous non-small cell lung cancer (NSCLC).
2) The study met its primary endpoint, finding that pemetrexed maintenance significantly reduced the risk of disease progression compared to placebo (HR=0.62, p<0.0001).
3) Updated results showed pemetrexed maintenance also significantly improved overall survival compared to placebo, with median OS of 13.9 months vs 11 months (HR=0.78, p=0.0199).
Role of molecular targeted therapy in HCC DubaiPAIRS WEB
This document discusses hepatocellular carcinoma (HCC) and approaches to treating this growing clinical challenge. It provides background on HCC pathogenesis and prognostic factors such as tumor stage, liver function, and tumor biology. Treatment options including curative therapies for early stage disease and palliative options for advanced HCC are described. The role of the targeted therapy sorafenib in treating advanced HCC is summarized based on results from Phase III trials showing it can prolong both overall survival and time to progression compared to placebo. Ongoing research into additional targeted agents and combination approaches for HCC are also mentioned.
El documento describe los resultados del estudio COU-AA-302 sobre el uso de abiraterona más prednisona versus placebo más prednisona en pacientes con cáncer de próstata resistente a la castración y sin quimioterapia previa. El estudio encontró que la abiraterona aumentó significativamente la supervivencia global y el tiempo libre de progresión radiográfica en comparación con el placebo.
Este documento describe la inmunoterapia en el cáncer. Explica que hay 12.7 millones de nuevos casos de cáncer cada año y 7.6 millones de muertes, y que la incidencia y mortalidad están aumentando en países en desarrollo. La inmunoterapia es una parte central del tratamiento del cáncer y manipula el sistema inmune para activar la inmunidad antitumoral. Existen varias clases de tratamiento como quimioterapia, terapia hormonal e inmunoterapia.
El documento resume los avances en inmunoterapia antitumoral. Explica que las terapias convencionales como quimioterapia y radioterapia han aumentado la supervivencia pero no curan los cánceres más comunes. La inmunoterapia es más prometedora porque explota las diferencias antigénicas entre células tumorales y normales. Se han logrado regresiones con citocinas, anticuerpos monoclonales y terapias celulares adoptivas. La investigación actual busca superar las limitaciones de especificidad y potencia de los
Presentación realizada por la Dra. Dolores Isla del
Servicio de Oncología Médica del Hospital Clínico Universitario Lozano Blesa de Zaragoza, en el marco de la I Jornada de actualización e innovación en Oncología que tuvo lugar en el CIBA en enero de 2015.
Este documento resume las opciones de tratamiento para el cáncer de páncreas, incluyendo la neoadyuvancia, adyuvancia y radioterapia paliativa. La neoadyuvancia con quimiorradiación aumenta la supervivencia y los márgenes quirúrgicos negativos. La adyuvancia con quimiorradiación no aumentó la supervivencia en ESPAC-1, pero la quimioterapia adyuvante sola sí lo hizo. Los estudios comparan diferentes regímenes de quimioterapia adyuvante.
Este documento presenta una guía de práctica clínica para la detección temprana, diagnóstico, tratamiento, seguimiento y rehabilitación del cáncer de próstata en Colombia. La guía fue desarrollada por un grupo multidisciplinario liderado por la Sociedad Colombiana de Urología y el Instituto Nacional de Cancerología, con apoyo de Colciencias. El objetivo es proveer recomendaciones basadas en evidencia para mejorar la atención de pacientes con cáncer de próstata en el país.
El cáncer de próstata es el tipo de cáncer más frecuente en los varones es principalmente una enfermedad de los ancianos y su incidencia aumenta con la edad. La mayoría de los casos se produce en varones mayores de 65 años.
El cáncer de próstata es un problema de salud importante en los ancianos pero la tasa de mortalidad es cada vez menos gracias a los avances en el diagnóstico y tratamiento.
Cuando se diagnostica pronto tiene cura. Cuando está limitado a la próstata en el momento del diagnóstico la tasa de supervivencia a los 5 años es del 100%. Incluso cuando el cáncer se ha extendido de manera local, aproximadamente el 95% de los pacientes sobreviven a los 5 años.
En muchos varones se ha encontrado cáncer de próstata en la autopsia. Generalmente no produce manifestaciones o complicaciones.
El documento describe el descubrimiento de que las células de cáncer de próstata son sensibles a los andrógenos y cómo esto llevó al desarrollo del tratamiento de deprivación androgénica. También discute cómo el cáncer de próstata eventualmente se vuelve resistente a la castración a pesar de los muy bajos niveles de andrógenos, y la importancia de reducir los andrógenos a niveles indetectables. Además, explica cómo la enzima CYP17 juega un papel clave en la persistencia
Más información en:
http://www.universidadpopularc3c.es/index.php/actividades/conferencias/event/2274
Ponente: Dra Yolanda Rodríguez Carrasco, Investigadora Titular del Centro Nacional de Biotecnología (CNB-CSIC)
Tema: Conferencia sobre el sistema inmunitario, como opera, etc.
Fecha: 5 de mayo de 2015
Lugar: Universidad Popular Carmen de Michelena de Tres Cantos.
Resumen:
El sistema inmunitario o inmunológico es aquel conjunto de estructuras y procesos biológicos en el interior de un organismo que lo protege contra enfermedades identificando y atacando a agentes patógenos y cancerosos. Detecta una amplia variedad de agentes, desde virus hasta parásitos intestinales, y necesita distinguirlos de las propias células y tejidos sanos del organismo para funcionar correctamente.
El sistema inmunitario se encuentra compuesto principalmente por leucocitos (linfocitos, otros leucocitos, anticuerpos, células T, citoquinas, macrófagos, neutrófilos, entre otros componentes que ayudan a su funcionamiento). La detección es complicada, ya que los patógenos pueden evolucionar rápidamente, produciendo adaptaciones que evitan el sistema inmunitario y permiten a los patógenos infectar con éxito a sus huéspedes.
Para superar este desafío, se desarrollaron múltiples mecanismos que reconocen y neutralizan patógenos. Incluso los sencillos organismos unicelulares como las bacterias poseen sistemas enzimáticos que los protegen contra infecciones virales. Otros mecanismos inmunitarios básicos se desarrollaron en antiguos eucariontes y permanecen en sus descendientes modernos, como las plantas, los peces, los reptiles y los insectos. Entre estos mecanismos figuran péptidos antimicrobianos llamados defensinas, la fagocitosis y el sistema del complemento.
Los vertebrados, como los humanos, tienen mecanismos de defensa aún más sofisticados. Los sistemas inmunitarios de los vertebrados constan de muchos tipos de proteínas, células, órganos y tejidos, los cuales se relacionan en una red elaborada y dinámica. Como parte de esta respuesta inmunitaria más compleja, el sistema inmunitario se adapta con el tiempo para reconocer patógenos específicos de manera más eficaz. A este proceso de adaptación se le llama "inmunidad adaptativa" o "inmunidad adquirida" capaz de poder crear una memoria inmunitaria. La memoria inmunitaria creada desde una respuesta primaria a un patógeno específico proporciona una respuesta mejorada a encuentros secundarios con ese mismo patógeno específico. Este proceso de inmunidad adquirida es la base de la vacunación.
Este documento resume la epidemiología, factores de riesgo, diagnóstico y tratamiento del cáncer de próstata. Reporta tasas de incidencia y mortalidad, factores como edad, raza y antecedentes familiares que influyen en el riesgo. Describe métodos de tamizaje como el PSA, biopsia prostática y estadificación para determinar la extensión de la enfermedad. Finalmente, resume las opciones terapéuticas como cirugía, radioterapia, hormonoterapia y observación según el estadio y
Este documento trata sobre la inmunoterapia. Explica la producción de anticuerpos monoclonales y su uso en tratamientos oncológicos. También discute el uso de citoquinas en terapia sistémica e inmunización génica, así como vacunas, terapia de enfermedades autoinmunes, alergias y prevención del rechazo de trasplantes.
Este documento trata sobre el cáncer de próstata. Explica que es el segundo tumor más frecuente en hombres y se diagnostican alrededor de 700,000 nuevos casos por año en todo el mundo. En Colombia, uno de cada tres hombres mayores de 50 años tiene cáncer de próstata. Describe la anatomía de la próstata y los factores de riesgo como la edad y la raza. Explica los síntomas, exámenes de diagnóstico como el tacto rectal y el PSA, y los diferentes tratamientos como la cirug
El documento proporciona información sobre diferentes tipos de inmunoterapia, incluyendo inmunización activa e inmunización pasiva. También describe varias vacunas específicas como vacunas contra enfermedades bacterianas como la difteria, la tosferina y la fiebre tifoidea, y vacunas contra enfermedades virales como el sarampión, la rubéola y la poliomielitis. Además, explica brevemente conceptos como la composición de las vacunas, los tipos de vacunas disponibles y sus dosis y esquemas de vac
CANCER DE PROSTATA Tratamiento con radioterapia externa de intensidad modulad...paliza aldo
Este documento resume los resultados de un estudio sobre 50 pacientes con cáncer de próstata tratados con radioterapia externa a altas dosis. Se administró una dosis de 76 Gy usando una técnica combinada de 3D-CRT e IMRT. La toxicidad aguda gastrointestinal fue de Grado 2 en el 18% de los pacientes y la toxicidad aguda genitourinaria fue de Grado 2 en el 44%. La toxicidad tardía gastrointestinal fue de Grado 2 en el 4% y la toxicidad tardía genitourinaria fue de Grado 2 en el 8%. El estudio con
El documento resume las diferentes opciones de tratamiento para el cáncer de próstata, incluyendo terapia expectante, cirugía prostática radical, radioterapia externa e interna, terapia hormonal y quimioterapia. Explica los factores a considerar para elegir un tratamiento, como la edad, estado de salud y expectativa de vida del paciente, así como el estadio y grado del tumor. Describe los beneficios y riesgos de cada opción terapéutica y resume los resultados reportados en estudios sobre las tasas de supervivencia libre
Manejo del cancer de próstata resistente a castración , fisiopatología, mecanismos de resistencia a la castración, manejo de segunda línea, quimioterapia citotóxica e inmunoterapia.
Este documento describe diferentes modalidades de tratamiento para el cáncer de próstata, incluyendo radioterapia, tratamiento quirúrgico, terapia hormonal y tratamientos para cáncer hormono resistente. Se discuten los efectos, indicaciones y efectos secundarios de cada modalidad.
El documento proporciona una introducción general a la inmunoterapia. Resume que la inmunoterapia modifica la respuesta inmune e induce tolerancia a los alérgenos. También describe los tipos de extractos alergénicos utilizados, el proceso de fabricación y las consideraciones de calidad asociadas con las vacunas. Finalmente, ofrece una guía sobre el manejo práctico de la inmunoterapia, incluida la administración, seguimiento y seguridad del tratamiento.
Dr. José Antonio Ortega Martell
Universidad Autónoma del Edo. de Hidalgo. Pachuca, Hidalgo. México.
IX Congreso Colombiano de Alergia, Asma e Inmunología.
Integración de la inmunoterapia en NSCLCMauricio Lema
This document discusses immunotherapy integration for NSCLC in the second line setting. It summarizes:
1) Key mechanisms of tumor immunology including PD-1/PD-L1 interactions and how they can be targeted by drugs like pembrolizumab.
2) Outcomes from first-line chemotherapy for NSCLC, noting median OS of 10-12 months and ORR of 30%.
3) Results from KEYNOTE-024 showing superior PFS and OS for pembrolizumab compared to chemotherapy as first-line treatment in patients with PD-L1 expression ≥50%.
Dr. Manuel Hidalgo - Simposio Internacional ' Terapias oncológicas avanzadas'Fundación Ramón Areces
Los días 15 y 16 de octubre de 2014, la Fundación Ramón Areces y la Real Academia Nacional de Farmacia, en colaboración con la Fundación de la Innovación Bankinter, reunieron en Madrid a algunos de los mayores expertos mundiales en nuevas terapias contra el cáncer. El Simposio Internacional, coordinado por la profesora y académica María José Alonso, analizó el momento actual de la lucha contra esta enfermedad. También fue un punto de encuentro para científicos de los más innovadores institutos de investigación en oncología, quienes debatieron sobre tres grandes temas: la Medicina Personalizada contra el cáncer, los nanomedicamentos en la terapia del cáncer y las terapias basadas en la inmunomodulación.
This document discusses a clinical trial comparing cisplatin-based chemoradiotherapy to cetuximab-based chemoradiotherapy for p16-positive oropharyngeal cancer. The trial found that while overall toxicity was similar between the two arms, serious adverse events were significantly more common with cisplatin treatment. However, patients receiving cisplatin chemoradiotherapy experienced significantly better 2-year overall survival and lower recurrence rates compared to those receiving cetuximab chemoradiotherapy. The findings suggest that for HPV-positive oropharyngeal cancer, cisplatin chemoradiotherapy provides excellent survival outcomes despite greater toxicity risks compared to cetuximab chemoradiotherapy.
1) A phase 3 trial compared nivolumab to everolimus in advanced renal cell carcinoma patients who had received 1-2 prior anti-angiogenic therapies. Nivolumab demonstrated significantly longer overall survival compared to everolimus, with median overall survival of 25 months versus 19.6 months.
2) Nivolumab had a higher objective response rate compared to everolimus (25% vs 5%) and longer median duration of response.
3) The overall survival benefit of nivolumab was consistent across patient subgroups and was independent of PD-L1 expression levels.
4-yr OS after 2nd-line Nivolumab, pooled analysis (based on Scott Antonia pre...Mauricio Lema
This document discusses long-term survival outcomes with nivolumab treatment in patients with previously treated advanced non-small cell lung cancer. It finds that early disease control, defined as stable or shrinking tumors after 3 months of treatment, as well as achieving an objective response, are associated with improved long-term survival. Patients who achieved early disease control had a median overall survival of 49.2 months compared to 11.3 months for those without early disease control. Similarly, patients who achieved an objective response had a median overall survival of not reached compared to 11.4 months for non-responders. The study demonstrates that nivolumab provides long-term survival benefits in this patient population.
Advances in immunotherapy, including checkpoint inhibitors targeting CTLA-4 and PD-1, have significantly improved outcomes for patients with metastatic melanoma. Combination immunotherapy with nivolumab and ipilimumab produces response rates over 60%, compared to around 40% for nivolumab alone and 11% for ipilimumab alone. Many patients receiving the combination immunotherapy continue to respond even after stopping treatment, achieving a state of treatment-free survival. While combination immunotherapy is more toxic than single-agent treatments, the toxicities are often manageable. Ongoing research continues to explore optimizing combination immunotherapy regimens to improve outcomes while reducing toxicity.
Immunotherapy for Metastatic Triple Negative Breast Cancerbkling
Sylvia Adams, MD, medical oncologist, and associate professor at the NYU School of Medicine, discusses the latest research including the role of immunology in the treatment of triple negative metastatic breast cancer. This webinar was hosted on October 19, 2016.
This document provides an overview of immunotherapy and how it works to treat cancer. It discusses the different types of T cells like CD4+ helper T cells and CD8+ cytotoxic T cells. It describes antigen presenting cells and their role in activating T cells. It explains how tumors evade immune surveillance and the factors that allow this. It discusses different immunotherapy approaches like blocking the CTLA-4 and PD-1 pathways with drugs like ipilimumab and nivolumab. Clinical trial results are summarized that show improved survival with these immunotherapies compared to chemotherapy in cancers like melanoma. Combination approaches are also discussed.
This document provides an overview of immunotherapy and how it works to treat cancer. It discusses the roles of T cells, antigen presenting cells, and cytokines in the immune response. It describes how tumors evade immune surveillance and strategies used in immunotherapy to overcome tumor resistance, such as blocking inhibitory receptors like CTLA-4 and PD-1 to reactivate T cells. Several studies are summarized that show improved survival outcomes for cancers like melanoma when treated with immunotherapies like nivolumab compared to chemotherapy. Combination approaches blocking multiple pathways are also discussed.
Renal Cell Carcinoma A New Standard Of Carefondas vakalis
This document summarizes the current standard of care for renal cell carcinoma (RCC), focusing on targeted therapies such as anti-angiogenesis agents. It reviews the biology and risk factors for RCC, the clinical efficacy and safety profiles of drugs like sorafenib and sunitinib, and phase III trial results demonstrating improved progression-free and overall survival compared to interferon-alpha. It concludes that anti-angiogenic therapies such as sorafenib, sunitinib, and temsirolimus have become the new standard first-line treatment for metastatic RCC based on superior clinical outcomes over existing immunotherapy options.
Lung cancer is a leading cause of cancer death. Immunotherapy using immune checkpoint inhibitors that target proteins like PD-1 and PD-L1 has shown promise in treating lung cancer. A study presented at ASCO 2015 found that treatment with the PD-L1 inhibitor atezolizumab resulted in improved survival for NSCLC patients with higher levels of PD-L1 expression on tumor cells compared to docetaxel chemotherapy. Another study showed nivolumab, a PD-1 inhibitor, improved survival over docetaxel as a treatment for advanced non-squamous NSCLC after chemotherapy, with greater benefit seen in patients with higher PD-L1 expression levels. These results suggest PD-L1 expression can help identify
This document discusses treatment options for advanced non-small cell lung cancer (NSCLC). It summarizes findings from clinical trials comparing chemotherapy drugs and combinations, and evaluates the benefits of adding targeted therapies like bevacizumab and EGFR inhibitors to chemotherapy. Key results showed that platinum-based doublet chemotherapy improves survival compared to best supportive care, and adding bevacizumab to paclitaxel and carboplatin further improves outcomes. Studies also found EGFR inhibitors gefitinib and erlotinib provide benefits for NSCLC patients with EGFR mutations.
Advances in Immunotherapy for Non-Small Cell Lung Cancerflasco_org
This document summarizes advances in immunotherapy for non-small cell lung cancer (NSCLC). It discusses results from key clinical trials of immunotherapy in both first-line and second-line settings for advanced NSCLC. It also reviews studies combining immunotherapy with chemotherapy, including evidence that combinations can provide benefits over chemotherapy alone. Emerging data on biomarkers like tumor mutational burden are presented. Future areas of research highlighted include neoadjuvant studies and investigating immunotherapy mechanisms through translational research.
This document summarizes several presentations from the 2014 American Society of Hematology (ASH) Annual Meeting regarding chronic myeloid leukemia (CML), multiple myeloma, and lymphoma. For CML, early results from the Phase III EPIC trial found that ponatinib resulted in deeper and more rapid responses compared to imatinib but with increased toxicity. Subset analyses of the PACE trial demonstrated that early molecular responses to ponatinib correlated with improved long-term outcomes. For multiple myeloma, updated criteria were presented for diagnosis. The Phase III FIRST trial showed that continuous lenalidomide and dexamethasone improved progression-free survival compared to fixed-duration regimens or melphalan, prednisone
1) Adjuvant chemotherapy reduces breast cancer mortality by 17-33% according to meta-analyses, with anthracycline-based regimens being more effective than CMF.
2) For HER2-positive early breast cancer, adjuvant chemotherapy plus trastuzumab is the standard of care, improving disease-free and overall survival compared to chemotherapy alone.
3) For endocrine-responsive early breast cancer, the absolute benefit of chemotherapy depends on risk factors; genomic signatures can help identify patients most likely to benefit from chemotherapy in addition to endocrine therapy.
1) Adjuvant chemotherapy reduces breast cancer mortality by 17-33% according to meta-analyses, with anthracycline-based regimens being more effective than CMF.
2) For HER2-positive early breast cancer, adjuvant chemotherapy plus trastuzumab is the standard of care, improving disease-free and overall survival compared to chemotherapy alone.
3) For endocrine-responsive early breast cancer, the absolute benefit of chemotherapy depends on risk factors; genomic signatures can help identify patients most likely to benefit from chemotherapy in addition to endocrine therapy.
This document proposes treatment algorithms for advanced non-small cell lung cancer (NSCLC) based on histology, predictive biomarkers, and other factors. It discusses the interrelationships between histology, maintenance therapy, and biomarkers. The document also reviews several studies that demonstrate improved progression-free survival with maintenance therapy after first-line chemotherapy compared to placebo, especially for patients with stable disease after induction. Overall survival benefits with maintenance therapy were more modest or not statistically significant in most trials. The goal of maintenance therapy is to prolong disease control, maintain tolerability, and improve overall survival.
El documento describe la historia y desarrollo de los recursos bibliográficos médicos, incluyendo el Index Medicus creado en 1879, MEDLARS en 1964, MEDLINE en 1971 y PubMed en 1997. Explica cómo PubMed ofrece acceso gratuito a más de 25 millones de referencias biomédicas de miles de revistas con más del 80% incluyendo resúmenes. Proporciona detalles sobre cómo la información en PubMed está organizada en campos y cómo se pueden realizar búsquedas efectivas utilizando descriptores MeSH, operadores boolean
2016-02 Toxicidades de los nuevos fármacos en cáncer renalMartín Lázaro
Este documento presenta los resultados de varios estudios sobre el tratamiento con inhibidores de TKI y mTOR en pacientes con cáncer renal. Resume los principales efectos secundarios de estos fármacos como hipertensión, fatiga, toxicidad cutánea y mucosa, e hipotiroidismo, así como estrategias para su manejo. También analiza la correlación entre algunos efectos adversos como la hipertensión y la eficacia del tratamiento.
Este documento resume las recomendaciones de un grupo de expertos sobre el tratamiento del cáncer de próstata resistente a la castración. Definen la resistencia a la castración como un aumento del PSA con niveles de testosterona por debajo de 50 ng/dL. Recomiendan no tratar con inhibidores de los osteoclastos a pacientes castration-naive ni a pacientes sin metástasis. En pacientes asintomáticos con metástasis, el tratamiento hormonal preferido es enzalutamida o abiraterona. Discut
Este documento presenta un algoritmo de tratamiento para el cáncer de pulmón no microcítico avanzado. Detalla los regímenes de quimioterapia y terapias dirigidas recomendadas para pacientes con mutaciones específicas como EGFR, ALK o BRAF. También resume los resultados clave de varios estudios que evaluaron la eficacia y seguridad de bevacizumab en combinación con quimioterapia de primera línea.
Este documento resume la incidencia, pronóstico y tratamiento de las metástasis cerebrales en diferentes tipos de cáncer. La incidencia es mayor en cáncer de pulmón (20-40%), melanoma (10-50%) y cáncer renal (7-10%). El pronóstico depende de factores como la edad, el estado funcional y la presencia de metástasis extracraneales. El tratamiento incluye corticoides, radioterapia, cirugía, quimioterapia y nuevos fármacos como TKIs, con bu
2015-04 Metástasis cerebrales en NSCLC y TKIsMartín Lázaro
1) El tratamiento de las metástasis cerebrales incluye radioterapia holocraneal y nuevos fármacos como los TKI, que pueden administrarse de forma concomitante o secuencial.
2) Los TKI que bloquean EGFR y ALK muestran altas tasas de respuesta en pacientes con mutaciones en esos genes, especialmente cuando se administran como monoterapia en pacientes asintomáticos.
3) Aunque el sistema nervioso central puede ser un "santuario" para algunos tumores, los TKI dirigidos a
2014-10 Efecto de vinflunina sobre la angiogénesis y la TEMMartín Lázaro
1. La vinflunina actúa inhibiendo la polimerización de los microtúbulos y alterando su dinámica para detener la mitosis. 2. También tiene actividad antiangiogénica al inhibir la morfogénesis endotelial y la neovascularización, y actividad sobre la transición epitelio-mesénquima al aumentar marcadores epiteliales y disminuir marcadores mesenquimales. 3. Un estudio clínico mostró que la vinflunina prolonga la supervivencia global en pacientes con cáncer de vej
El documento resume la evolución del diagnóstico y tratamiento de los tumores de origen desconocido (TOD). Se ha pasado de definiciones basadas en imagen a clasificaciones por inmunohistoquímica (IHQ) y perfiles moleculares que permiten tratamientos más específicos. La combinación de IHQ y perfiles de expresión génica mejora la precisión en la identificación del primario en comparación con la IHQ sola. La mayoría de los TOD presentan alteraciones moleculares diana para nuevos fármacos.
Este documento resume varios estudios sobre el uso de quimioterapia adyuvante en el cáncer de pulmón no microcítico. Los estudios más grandes y consistentes han encontrado que la combinación de cisplatino y vinorelbina mejora la supervivencia global, especialmente en los estadios II y III. Un estudio prospectivo de fase II de 154 pacientes evaluó el uso de vinorelbina oral el día 8 junto con cisplatino o carboplatino como tratamiento adyuvante y encontró una supervivencia del 69.8% a los 3 años.
This document summarizes new strategies for treating renal cancer and their impact on overall survival. It discusses several clinical trials that evaluated targeted therapies like sunitinib, sorafenib, bevacizumab, temsirolimus, everolimus, pazopanib, and axitinib. The selection of the appropriate treatment for each patient subgroup and line of therapy is key to improving patient overall survival. While targeted therapies have increased median progression-free survival and overall survival compared to cytokines, sequencing trials have been inconclusive and real-world outcomes lag behind clinical trials.
Importancia de la situación general en el paciente con cáncer 2014Martín Lázaro
El documento describe la importancia del Performance Status (PS) en oncología como síntoma y factor pronóstico de la enfermedad. Las escalas más utilizadas para medir el PS son la escala de Karnofsky y la escala ECOG. Un PS más bajo se asocia con una supervivencia menor. Estas escalas son útiles para predecir el pronóstico, tomar decisiones sobre el tratamiento y estratificar a los pacientes en estudios de investigación.
Importancia de la edad y comorbilidad en el paciente con cáncerMartín Lázaro
1) La comorbilidad y la edad son factores que limitan las maniobras de diagnóstico y tratamiento en pacientes con cáncer. 2) Los pacientes mayores tienen más condiciones comórbidas y reciben tratamientos con intención curativa con menor probabilidad, a pesar de que algunos estudios muestran que pueden beneficiarse igual que pacientes más jóvenes. 3) La evaluación geriátrica integral es importante para identificar el riesgo clínico y guiar decisiones sobre el tratamiento en pacientes ancianos con cáncer.
2014-02 Manejo toxicidades nuevos fármacos ca renalMartín Lázaro
Este documento resume los principales efectos adversos asociados con el tratamiento con inhibidores de tirosina quinasa y mTOR en pacientes con cáncer renal avanzado. Algunas toxicidades como la hipertensión y la fatiga se asocian con una mejor eficacia del tratamiento. El manejo de las toxicidades requiere un monitoreo cuidadoso y ajustes de dosis para maximizar los beneficios del tratamiento y la calidad de vida del paciente.
Estudios fase III necesarios para aprobar un fármaco: a favor 12-2013Martín Lázaro
El documento discute los requisitos para justificar el uso clínico de un fármaco. Mientras que tradicionalmente se ha requerido al menos un estudio de fase III, el documento argumenta que esto no siempre es necesario y que la evidencia de estudios de fase II puede ser suficiente en algunos casos, especialmente si los estudios de fase II son aleatorizados y tienen objetivos claros. También señala que los estudios de un solo brazo tienen más probabilidades de errores y sesgos.
Este documento presenta el caso de una mujer de 68 años diagnosticada con adenocarcinoma de pulmón con mutación EGFR positiva en el exón 19. Se describe su tratamiento inicial con erlotinib, un inhibidor de tirosina quinasa dirigido, que duplicó su supervivencia libre de progresión en comparación con la quimioterapia estándar, con una tasa de respuesta tres veces mayor. El documento resume los beneficios del tratamiento dirigido con inhibidores de EGFR en pacientes con mutación EGFR.
Este documento resume los resultados de ensayos clínicos de fase II y III que evalúan la eficacia y seguridad de la vinflunina en el tratamiento del cáncer de vejiga avanzado tras fallo a platino. Los ensayos de fase II mostraron tasas de respuesta global del 15-18% y una mediana de supervivencia sin progresión de 2,8-3 meses. El ensayo de fase III encontró que la vinflunina prolongó la supervivencia global en 2,3 meses e incrementó las tasas de respuesta y control
Retratamiento docetaxel cáncer de próstata 2013-06Martín Lázaro
El documento analiza las opciones de retratamiento con docetaxel en pacientes con cáncer de próstata metastásico hormonosensible resistente. Se revisan varios estudios retrospectivos que muestran tasas de respuesta del PSA entre el 24-66% y una supervivencia global mediana de 13-22 meses con retratamiento con docetaxel. Los pacientes que responden mejor son los que tuvieron una progresión a docetaxel previo mayor a 6 meses. El retratamiento con docetaxel es una opción razonable en ausencia de otras
Ca próstata: cuando la quimioterapia está indicada 05-2013Martín Lázaro
Este documento describe el tratamiento del cáncer de próstata resistente a la castración. Existen dos tipos de pacientes según su respuesta a la terapia hormonal: sensibles o resistentes. Se detallan las opciones de tratamiento de segunda línea como la quimioterapia o nuevos fármacos. Finalmente, se analizan factores pronósticos que pueden predecir la supervivencia de los pacientes.
Post-ASCO GU ca renal: Nuevas dianas y combinaciones 2013-05Martín Lázaro
El documento presenta los resultados de varios estudios clínicos que evalúan combinaciones de nuevos fármacos para el tratamiento del cáncer de riñón avanzado. Se muestran los efectos secundarios de diferentes combinaciones y se resumen brevemente los resultados de estudios fase I/II de combinaciones como bevacizumab-everolimus, sunitinib-temsirolimus y sorafenib-everolimus. También se presentan datos de estudios evaluando fármacos como entinostat, levantinib, AGS-003 e inmunoterapia con
Tumores NE de célula grande de pulmón 2013-06Martín Lázaro
Este documento resume los tratamientos para tumores neuroendocrinos de célula grande de pulmón. Describe que la cirugía es el tratamiento estándar para estadios iniciales y que el tratamiento adyuvante puede mejorar la supervivencia. Para enfermedad avanzada, la quimioterapia basada en regímenes de pequeña célula como cisplatino más etopósido parece ser la opción más efectiva.
NVBDCP.pptx Nation vector borne disease control programSapna Thakur
NVBDCP was launched in 2003-2004 . Vector-Borne Disease: Disease that results from an infection transmitted to humans and other animals by blood-feeding arthropods, such as mosquitoes, ticks, and fleas. Examples of vector-borne diseases include Dengue fever, West Nile Virus, Lyme disease, and malaria.
Muktapishti is a traditional Ayurvedic preparation made from Shoditha Mukta (Purified Pearl), is believed to help regulate thyroid function and reduce symptoms of hyperthyroidism due to its cooling and balancing properties. Clinical evidence on its efficacy remains limited, necessitating further research to validate its therapeutic benefits.
- Video recording of this lecture in English language: https://youtu.be/kqbnxVAZs-0
- Video recording of this lecture in Arabic language: https://youtu.be/SINlygW1Mpc
- Link to download the book free: https://nephrotube.blogspot.com/p/nephrotube-nephrology-books.html
- Link to NephroTube website: www.NephroTube.com
- Link to NephroTube social media accounts: https://nephrotube.blogspot.com/p/join-nephrotube-on-social-media.html
Here is the updated list of Top Best Ayurvedic medicine for Gas and Indigestion and those are Gas-O-Go Syp for Dyspepsia | Lavizyme Syrup for Acidity | Yumzyme Hepatoprotective Capsules etc
share - Lions, tigers, AI and health misinformation, oh my!.pptxTina Purnat
• Pitfalls and pivots needed to use AI effectively in public health
• Evidence-based strategies to address health misinformation effectively
• Building trust with communities online and offline
• Equipping health professionals to address questions, concerns and health misinformation
• Assessing risk and mitigating harm from adverse health narratives in communities, health workforce and health system
Does Over-Masturbation Contribute to Chronic Prostatitis.pptxwalterHu5
In some case, your chronic prostatitis may be related to over-masturbation. Generally, natural medicine Diuretic and Anti-inflammatory Pill can help mee get a cure.
Integrating Ayurveda into Parkinson’s Management: A Holistic ApproachAyurveda ForAll
Explore the benefits of combining Ayurveda with conventional Parkinson's treatments. Learn how a holistic approach can manage symptoms, enhance well-being, and balance body energies. Discover the steps to safely integrate Ayurvedic practices into your Parkinson’s care plan, including expert guidance on diet, herbal remedies, and lifestyle modifications.
Recomendações da OMS sobre cuidados maternos e neonatais para uma experiência pós-natal positiva.
Em consonância com os ODS – Objetivos do Desenvolvimento Sustentável e a Estratégia Global para a Saúde das Mulheres, Crianças e Adolescentes, e aplicando uma abordagem baseada nos direitos humanos, os esforços de cuidados pós-natais devem expandir-se para além da cobertura e da simples sobrevivência, de modo a incluir cuidados de qualidade.
Estas diretrizes visam melhorar a qualidade dos cuidados pós-natais essenciais e de rotina prestados às mulheres e aos recém-nascidos, com o objetivo final de melhorar a saúde e o bem-estar materno e neonatal.
Uma “experiência pós-natal positiva” é um resultado importante para todas as mulheres que dão à luz e para os seus recém-nascidos, estabelecendo as bases para a melhoria da saúde e do bem-estar a curto e longo prazo. Uma experiência pós-natal positiva é definida como aquela em que as mulheres, pessoas que gestam, os recém-nascidos, os casais, os pais, os cuidadores e as famílias recebem informação consistente, garantia e apoio de profissionais de saúde motivados; e onde um sistema de saúde flexível e com recursos reconheça as necessidades das mulheres e dos bebês e respeite o seu contexto cultural.
Estas diretrizes consolidadas apresentam algumas recomendações novas e já bem fundamentadas sobre cuidados pós-natais de rotina para mulheres e neonatos que recebem cuidados no pós-parto em unidades de saúde ou na comunidade, independentemente dos recursos disponíveis.
É fornecido um conjunto abrangente de recomendações para cuidados durante o período puerperal, com ênfase nos cuidados essenciais que todas as mulheres e recém-nascidos devem receber, e com a devida atenção à qualidade dos cuidados; isto é, a entrega e a experiência do cuidado recebido. Estas diretrizes atualizam e ampliam as recomendações da OMS de 2014 sobre cuidados pós-natais da mãe e do recém-nascido e complementam as atuais diretrizes da OMS sobre a gestão de complicações pós-natais.
O estabelecimento da amamentação e o manejo das principais intercorrências é contemplada.
Recomendamos muito.
Vamos discutir essas recomendações no nosso curso de pós-graduação em Aleitamento no Instituto Ciclos.
Esta publicação só está disponível em inglês até o momento.
Prof. Marcus Renato de Carvalho
www.agostodourado.com
TEST BANK For Community Health Nursing A Canadian Perspective, 5th Edition by...Donc Test
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Basavarajeeyam is an important text for ayurvedic physician belonging to andhra pradehs. It is a popular compendium in various parts of our country as well as in andhra pradesh. The content of the text was presented in sanskrit and telugu language (Bilingual). One of the most famous book in ayurvedic pharmaceutics and therapeutics. This book contains 25 chapters called as prakaranas. Many rasaoushadis were explained, pioneer of dhatu druti, nadi pareeksha, mutra pareeksha etc. Belongs to the period of 15-16 century. New diseases like upadamsha, phiranga rogas are explained.
ABDOMINAL TRAUMA in pediatrics part one.drhasanrajab
Abdominal trauma in pediatrics refers to injuries or damage to the abdominal organs in children. It can occur due to various causes such as falls, motor vehicle accidents, sports-related injuries, and physical abuse. Children are more vulnerable to abdominal trauma due to their unique anatomical and physiological characteristics. Signs and symptoms include abdominal pain, tenderness, distension, vomiting, and signs of shock. Diagnosis involves physical examination, imaging studies, and laboratory tests. Management depends on the severity and may involve conservative treatment or surgical intervention. Prevention is crucial in reducing the incidence of abdominal trauma in children.
4. ¿Por qué el cáncer de pulmón?
Figure: Somatic mutation frequencies observed in exomes from 3,083 tumor-normal pairs
Lawrence et al; Nature 499, 214–218 (11 July 2013)
Lung tumors along with other malignancies such as bladder and melanoma display
a high number of somatic mutations rendering these tumors more immunogenic
5. Tumor infiltrating FOXP3+ regulatory T-cells are associated
with recurrence in pathologic stage I NSCLC patients
Petersen RP. Cancer 2006;107(12):2866–72.
Foxp3+/CD3+ combination risk according
to IHC score
IHC scores
CD3,Foxp3
Low risk 3,0; 2,0
Intermediate risk 1,0; 2,1; 3,1; 3,2
High risk 0,0; 1,1; 2,2; 3,3
N=64
1996-2001
6. Brambilla E, J Clin Oncol. 2016 Feb 1.
Efecto pronóstico de la infiltración tumoral linfocítica en el
cáncer de pulmón no-microcítico resecable
16. 1. Mellman, et al. Nature 2011 2. Chen & Mellman. Immunity 2013
Anti-CTLA-4
CTLA-4 is a major negative regulator of T cell activation
and inhibition of CTLA-4 can enhance T cell stimulation,
resulting in more potent anti-tumour responses1
Ipilimumab
Tremelimumab
Anti-PDL1/PD1
PD-L1 expression on tumour cells and tumour-infiltrating
immune cells can inhibit T cell activity via its receptor PD-
1, dampening the anti-tumour immune response.
Inhibition of
PD-L1 or its receptor PD-1 may restore T cell effector
function2
Atezolizumab (anti-PDL1)
Durvalumab (anti-PDL1)
Nivolumab (anti-PD1)
Pembrolizumab (anti-PD1)
Avelumab (anti-PDL1)
BMS-936559 (anti-PDL1)
CTLA-4 pathway
PD-1 pathway
17. Ellis LM. J Clin Oncol; 2014 Apr 20;32(12):1277–80.
Summary of recommended targets for meaningful clinical trials goals:
Lung Cancer
Primary End Point Secondary End Point
Current
baseline
median
OS(m)
Improvement over
current OS that
would be clinically
meaningful (months)
Targets
HR
Improvement
in 1-year
survival rate
(%)
Improvement
in PFS
(months)
Lung cancer
Non-squamous
13 3.25-4 0.76-0.8 53 61 4
Lung cancer
Squamous
10 2.5-3 0.77-0.8 44 63 3
18. Agent Immunoth.
approach
Study design Population Results
SRL172
O’Brien
Ann Oncol 2014
Nonspecific
vaccine
(killed Mycob)
Open label: CT +
SLR172 (phase
III)
Stage III/IV
unresectable
NSCLC
Primary OS
endpoint not
met
Tecemotide
Butts
Lancet Oncol
2014
Tumor-specific
MUC1 vaccine
START:
Tecemotide vs
placebo
(phase III)
Stage III after
CT-RDT
Primary OS
endpoint not
met
MAGE-3
Vanteenkiste
ESMO 2014
Tumor specific
MAGE-3 vaccine
MAGRIT: MAGE-
vs placebo
Stage IB-IIIA
resected MAGE-
3 positive
Primary DFS
endpoint not
met
GVAX
Nemunaitis
Cancer Gen Ther
2006
Autologous
tumor cell
vaccine
GVAX alone
(phase I/II)
Advanced NSCLC No responses
Failed Immunotherapies tested in NSCLC
19. Agent Immunoth.
approach
Study design Population Results
Belagenpumatucel-L
Giaconne
ECCO 2014
TGF-b-
blocking
allogenic
tumor cell
vaccine
STOP:
maintenance vs
placebo (phase
III)
Stage III/IV
NSCLC; no
disease
progressión
after frontline
therapy
Primary OS
endpoint not
met; predefined
subgroups
benefit
Talactoferrin
Nemunaitis
Ann Oncol 2013
Dendritic cell
activation
FORTIS-M:
talactoferrine vs
placebo (phase
III)
Stage III/IV
NSCLC refractory
to 2 or more
therapies
Primary OS
endpoint not
met
CPG 7909
Manegold
Ann Oncol 2012
Dendritic cell
activation
Chemotherapy +
CPG 7909 (phase
III)
Stage III/IV
NSCLC naïve to
chemotherapy
Primary OS
endpoint not
met
Failed Immunotherapies tested in NSCLC
24. Fase II aleatorizado
N=87
Tremelimumab 15 mg/kg iv cada 90 d
No diferencias en SLP
Toxicidad grado ¾: 20.5%
RP en mantenimiento: 4.8%
SLP a los 3 meses: 21 vs 15%
Zatloukal, ASCO 2009; #8071
Randomized phase II clinical trial comparing tremelimumab with BSC
following first-line platinum-based therapy in pts with advanced NSCLC
26. Gettinger SN. J Clin Oncol; 2015 Jun 20;33(18):2004–12.
NIVOLUMAB: phase I dose-escalation cohort expansion trial
N=129
RR:17%
27. CheckMate 017: Nivolumab vs Docetaxel in
Previously Treated Squamous NSCLC
Open-label, randomized phase III trial
Primary endpoint: OS
Secondary endpoints: ORR, PFS, efficacy by PD-L1 expression,
safety, QoL
Pts with stage IIIB/IV
squamous NSCLC and ECOG
PS 0-1 with failure of 1
previous platinum doublet
chemotherapy
(N = 272)
Nivolumab 3 mg/kg IV q2w
(n = 135)
Docetaxel 75 mg/m2 IV q3w
(n = 137)
Until disease
progression or
unacceptable toxicity
Stratified by previous paclitaxel
therapy (yes vs no) and region
Spigel DR, et al. ASCO 2015. Abstract 8009. Brahmer J, et al. N Engl J Med. 2015;[Epub ahead of print].
28. CheckMate 017: Baseline Characteristics
Characteristic
Nivolumab
(n = 135)
Docetaxel
(n = 137)
Median age, yrs (range) 62 (39-85) 64 (42-84)
Male, % 82 71
Current/former smoker, % 90 94
ECOG PS 1, % 79 73
Stage IV disease,* % 78 82
CNS metastasis, % 7 6
Prior paclitaxel, % 34 34
PD-L1 expression,† %
≥ 1%
≥ 5%
≥ 10%
Not quantifiable
47
31
27
13
41
29
24
21
*Stage not reported in 1 pt in the nivolumab and 1 pt in the docetaxel groups.
†83% of pts had quantifiable PD-L1 expression. PD-L1 expression measured in pre-treatment tumor
biopsies with validated, automated immunohistochemical assay using PD-L1 antibody clone 28–8.
Spigel DR, et al. ASCO 2015. Abstract 8009. Brahmer J, et al. N Engl J Med. 2015;[Epub ahead of print].
29. Overall survival, PFS, and response: CheckMate 017
PFSOS
Reckamp K, et al. Presented at WCLC 2015, Abstract 736.
Nivolumab
(n=135)
Docetaxel
(n=137)
HR
Median OS, months 9.2 6.0 HR = 0.62 (0.48, 0.81); P =
0.0004
Median PFS, months 3.5 2.8 HR = 0.63 (0.48, 0.83); P =
0.0008
ORR, % 20 9 P = 0.008
Median DOR, months NR 8.4
Nivolumab
Docetaxel
12-mo OS rate = 42%
12-mo OS rate = 24%
OS(%)
Time (months)
30
100
90
80
70
60
50
40
30
10
0
20
33211815129630 2724
18-mo OS rate = 28%
18-mo OS rate = 13%
Nivolumab
Docetaxel
12-mo PFS rate = 21%
12-mo PFS rate = 6.4%
PFS(%)
Time (months)
30
100
90
80
70
60
50
40
30
10
0
20
211815129630 2724
18-mo PFS rate = 17%
18-mo PFS rate = 2.7%
30. OS and PFS by PD-L1 expression: CheckMate 017
83% de los pacientes: expresión de PD-L1 cuantificable
Beneficio independiente del nivel de expresión de PD-L1
PD-L1
expressiona
Patients, n Unstratified
HR (95% Cl)
Interaction
P-valueNivolumab Docetaxel
OS
≥1% 63 56 0.69 (0.45, 1.05)
0.56
<1% 54 52 0.58 (0.37, 0.92)
≥5% 42 39 0.53 (0.31, 0.89)
0.47
<5% 75 69 0.70 (0.47, 1.02)
≥10% 36 33 0.50 (0.28, 0.89)
0.41
<10% 81 75 0.70 (0.48, 1.01)
NQ 18 29 0.39 (0.19, 0.82)
PFS
≥1% 63 56 0.67 (0.44, 1.01)
0.70
<1% 54 52 0.66 (0.43, 1.00)
≥5% 42 39 0.54 (0.32, 0.90)
0.16
<5% 75 69 0.75 (0.52, 1.08)
≥10% 36 33 0.58 (0.33, 1.02)
0.35
<10% 81 75 0.70 (0.49, 0.99)
NQ 18 29 0.45 (0.23, 0.89)
PD-L1-negative expression
PD-L1-positive expression
NQ
0.25 1.0 2.0
Nivolumab Docetaxel
0.50.125
aPD-L1 expression was measured in pretreatment tumor biopsies (DAKO)
1. Brahmer J, et al. New Engl J Med. 2015;373:123–135. 2. Rizvi NA, et al. Lancet Oncol. 2015;16:257–265.
HR ± 95% CI
31. CheckMate 057: Nivolumab vs Docetaxel in
Previously Treated Non-Squamous NSCLC
Open-label, randomized phase III trial
Primary endpoint: OS
Secondary endpoints: ORR, PFS, efficacy by PD-L1 expression,
safety, QoL
Pts with stage IIIB/IV
squamous NSCLC and ECOG
PS 0-1 with failure of 1
previous platinum doublet
chemotherapy
(N = 582)
Nivolumab 3 mg/kg IV q2w
(n = 292)
Docetaxel 75 mg/m2 IV q3w
(n = 290)
Until disease
progression or
unacceptable toxicity
Borghaei H, Paz-Ares L, Horn L, Spigel DR, Steins M, Ready NE, et al. Nivolumab versus
Docetaxel in Advanced Nonsquamous Non–Small-Cell Lung Cancer. New England Journal of
Medicine. 2015 Sep 27;:150927150118000–13.
33. Overall survival and PFS: CheckMate 057
Paz-Ares L, et al. Presented at ASCO 2015, Abstract LBA109.
PFSOS
Nivolumab
Docetaxel
1-yr OS rate = 51%
1-yr OS rate = 39%
OS(%)
Time (months)
100
90
80
70
60
50
40
30
10
0
20
27211815129630 24
Nivolumab
Docetaxel
1-yr PFS rate = 19%
1-yr PFS rate = 8%
PFS(%)
Time (months)
100
90
80
70
60
50
40
30
10
0
20
27211815129630 24
Nivolumab
(n=292)
Docetaxel
(n=290)
HR
Median OS,
months 12.2 9.4 HR = 0.73 (96% CI: 0.59, 0.89); P = 0.0015
Median PFS,
months 2.3 4.2 HR = 0.92 (95% CI: 0.77, 1.11); P = 0.3932
ORR, % 19 12 P = 0.0246
Median DOR,
months 17.2 5.6
34. OS by PD-L1 expression: CheckMate 057
PD-L1 expression was predictive of benefit with nivolumab
Nivo
Doc
100
90
80
70
60
50
40
30
10
0
20
Time (months)
242118151
2
9630 27
Median
OS(mo)
Nivo 10.4
Doc 10.1
Median OS
(mo)
Nivo 17.2
Doc 9.0
≥1% PD-L1 expression
level
HR (95% CI)=0.59 (0.43, 0.82)
<1% PD-L1 expression
level
OS(%)
HR (95% CI)=0.90 (0.66, 1.24)
OS(%)
242118151
2
9630 27
100
90
80
70
60
50
40
30
10
0
20
Nivo
Doc
1. Paz-Ares L, et al. Presented at ASCO 2015, Abstract LBA109.
2. 2. Rizvi NA, et al. Lancet Oncol 2015;16:257–265.
PD-L1
expression level
Median OS (mo)
HR
Nivolumab Docetaxel
≥5%
<5%
18.2
9.7
8.1
10.1
HR (95% CI) = 0.43 (0.30, 0.63)
HR (95% CI) = 1.01 (0.77, 1.34)
≥10%
<10%
19.4
9.9
8.0
10.3
HR (95% CI) = 0.40 (0.26, 0.59)
HR (95% CI) = 1.00 (0.76, 1.31)
35. Overall survival by PD-L1 expression levels
Median OS
(months)
Nivo 17.7
Doc 9.0
Median OS
(months)
Nivo 19.4
Doc 8.1
Median OS
(months)
Nivo 19.9
Doc 8.0
Median OS
(months)
Nivo 10.5
Doc 10.1
Median OS
(months)
Nivo 9.8
Doc 10.1
Median OS
(months)
Nivo 9.9
Doc 10.3
≥1% PD-L1 expression level
Time (mos)
100
90
80
70
60
50
40
30
10
0
20
3024211815129630 27
OS(%)
HR (95% CI) = 0.58 (0.43, 0.79)
≥5% PD-L1 expression level100
90
80
70
60
50
40
30
10
0
20
3024211815129630 27
Time (mos)
HR (95% CI) = 0.43 (0.30, 0.62)
≥10% PD-L1 expression level100
90
80
70
60
50
40
30
10
0
20
3024211815129630 27
Time (mos)
HR (95% CI) = 0.40 (0.27, 0.58)
<1% PD-L1 expression level
100
90
80
70
60
50
40
30
10
0
20
3024211815129630 27
Time (mos)
OS(%)
Nivo
Doc
<10% PD-L1 expression level100
90
80
70
60
50
40
30
10
0
20
3024211815129630 27
Time (mos)
<5% PD-L1 expression level
100
90
80
70
60
50
40
30
10
0
20
3024211815129630 27
Time (mos)
HR (95% CI) = 0.87 (0.63, 1.19) HR (95% CI) = 0.96 (0.73, 1.27) HR (95% CI) = 0.96 (0.74, 1.25)
Based on a July 2, 2015 database lock.
Borghaei H, et al. N Engl J Med. 2015;373:1627-1639.
Nivo
Doc
36. Phase 2, single-arm study, stage IIIB/IV squamous NSCLC
65% of patients ≥3 prior systemic therapies; CheckMate 063
All patients
IRC assessed
(per RECIST
v1.1)
(N=117)
ORR, %a 15
Median DOR, mosa NR
Ongoing responders, %a 76
PFS rate at 1 year, %a 20
Grade 3–4 treatment-related AEs,
%
Fatigue
Diarrhea
Rash
17
4
3
1
IRC = independent review committee; NR = not reached
Horn L, et al. Presented at WCLC 2015, Abstract 828.
Nivolumab
Median OS = 8.1 mos
117 93 68 51 28 5 0 0 00
117 93 69 54 45 38 30 24 06
July 2014 DBL
June 2015 DBL
Number of Patients at Risk
Nivolumab 3 mg/kg
18-mos OS = 27%
OS(%)
Time (months)
100
90
80
70
60
50
40
30
10
0
20
27211815129630 24
37. Vansteenkiste et al. Ann Oncol 2015; 26 (suppl 6): abstr 14LBA
Atezolizumab monotherapy vs docetaxel in 2L/3L non-small cell lung cancer:
Primary analyses for efficacy, safety and predictive biomarkers from a randomized
phase II study (POPLAR)
38. Atezolizumab was associated with significant improvements in OS in the ITT population
Median OS for atezolizumab was 12.6 months compared with 9.7 months for
docetaxel (HR 0.73 [95%CI 0.53, 0.99], p=0.040)
POPLAR: all patient efficacy
ITT OS (n=287)
Vansteenkiste et al. Ann Oncol 2015; 26 (suppl 6): abstr 14LBA
39. Subgroup (% of enrolled patients)
0.2 21
0.80
0.69
0.73
Hazard Ratio
In favor of atezolizumab In favor of docetaxel
ITT (N=287)
Squamous (34%)
Non-Squamous (66%)
Median OS (95% CI), mo
Atezolizumab Docetaxel
10.1 (6.7, 14.5) 8.6 (5.4, 11.6)
15.5 (9.8, NE) 10.9 (8.8, 13.6)
12.6 (9.7, 16.4) 9.7 (8.6, 12.0)
Vansteenkiste et al. Ann Oncol 2015; 26 (suppl 6): abstr 14LBA
POPLAR: OS by histology
40. • Patients with higher PD-L1 expression demonstrated improved OS with atezolizumab
• Tumour cells and tumour-infiltrating immune cells were both independent predictors of
survival improvement with atezolizumab
TC3 or IC3 (high) TC2/3 or IC2/3
TC1/2/3 or IC1/2/3 TC0 or IC0
41. Besse et al. Ann Oncol 2015; 26 (suppl 6): abstr 16LBA
Phase II, single-arm trial (BIRCH) of atezolizumab as first-line or subsequent
therapy for locally advanced or metastatic PD-L1-selected non-small cell
lung cancer (NSCLC)
42. ORR by line of therapy
TC3 or IC3 and TC2/3 or IC2/3 subgroups
Besse et al. Ann Oncol 2015; 26 (suppl 6): abstr 16LBA
43. Besse et al. Ann Oncol 2015; 26 (suppl 6): abstr 16LBA
BIRCH: Overall Survival by Line of Therapy
TC2/3 or IC2/3
Subgroup Median OS, mo
(95% CI)
6-mo OS,
%
1L (Cohort 1) 14.0 (14.0, NE) 82%
2L (Cohort 2) NE (11.2, NE) 76%
3L+ (Cohort 3) NE (8.4, NE) 71%
44. Besse et al. Ann Oncol 2015; 26 (suppl 6): abstr 16LBA
Subgroup Median OS, mo
(95% CI)
6-mo OS,
%
1L (Cohort 1) NE (10.4, NE) 79%
2L (Cohort 2) NE (10.6, NE) 80%
3L+ (Cohort 3) NE (NE, NE) 75%
BIRCH: Overall Survival by Line of Therapy
TC3 or IC3
45. KEYNOTE-001: Subanalysis of Phase I
Pembrolizumab Trial in NSCLC
Administered tumor assessment: imaging every 9 wks
• Primary: RECIST v.1.1 (independent central
review)
• Secondary: immune-related response criteria
(irRC; investigator assessed)
• Tumor biopsy
• Tumor biopsy within 60 days prior to
first dose of pembrolizumab required
• Tumor PD-L1 expression determined
by prototype assay to inform
enrollment; Samples were
independently reanalyzed using
clinical trial IHC assay
Treatment-naive
or previously
treated
advanced
NSCLC
(N = 495)
Pembrolizumab IV
2 mg/kg q3w (n = 6)
Mandatory tumor biopsy
Pembrolizumab IV
10 mg/kg q3w (n = 287)
Pembrolizumab IV
10 mg/kg q2w (n = 202)
CR, PR, SD
PD, unacceptable
AE, or investigator
decision
Continue dosing
and assessments
every 9 wks
Off study
Garon EB. N Engl J Med. 2015 May 21;372(21):2018–28.
46. PD-L1 NSCLC Sample IHC Staining
Negative Weak positive
(1% to 49%)
PD-L1 = 0% positive PD-L1 = 2% positive PD-L1 = 100% positive
Strong positive
(50% to 100%)
Garon EB. N Engl J Med. 2015 May 21;372(21):2018–28.
47. 100
80
60
40
20
0
Keynote-001: Pembrolizumab Efficacy in Overall Population
All cohorts N ORR by RECIST, % (95% CI)
Total 495 19.4 (16.0-23.2)
Treatment naive 101 24.8 (16.7-34.4)
Previously treated 394 18.0 (14.4-22.2)
Nonsquamous 401 18.7 (15.0-22.9)
Squamous 85 23.5 (15.0-34.0)
PFS OS100
80
60
40
20
0
0 2 4 6 8 10 12 14 16 18 20 22 24 26
Mos
PFS,%
OS,%
0 4 8 12 16 20 24
Mos
28
All patients
Previously treated
Treatment-naïve
All patients
Previously treated
Treatment-naïve
Garon EB. N Engl J Med. 2015 May 21;372(21):2018–28.
52. Checkpoint inhibitors in 2/3L NSCLC
POPLAR
PhII allcomer 2/3L
atezo vs. doc
(n=287)
CheckMate 017
PhIII 2L Sq nivo vs. doc
(n=272)
CheckMate 057
PhIII 2L NSq nivo vs. doc
(n=582)
KEYNOTE-001
PhIb (inc. NSCLC)
pembro
(n=394 for
previously treated)
ORR,
%
Atezo 15% vs doc 15% Nivo 20% vs doc 9% Nivo 19% vs doc 12% Pembro 18%
Notes G3–4 treatment-related
AEs: 12 vs 39%
G3–4 treatment-related
AEs: 7 vs 55%
Reduction from baseline in lung
cancer symptoms with
nivolumab
G3–4 treatment-related
AEs: 10 vs 54%
Low incidence of
immune-related AEs
Refs. Spira, et al. ASCO 2015 Spigel, et al. ASCO 2015
Reckamp, et al. WCLC 2015
Gralla, et al. WCLC 2015
Paz-Ares, et al. ASCO 2015 Garon, et al. AACR 2015
Nivo
OS
Doc
OS
Pem
OS
Pem
PFS
Atezo
OS
Nivo
PFS
Doc
PFS
Nivo
OS
Doc
OS
Nivo
PFS
Doc
PFS
Doc
OS
Atezo
PFS
Doc
PFS
HR 0.59
p=0.00025
HR 0.62
p=0.0004
HR 0.73
p=0.0015
HR 0.92
p=0.3932
HR 0.77
p=0.1071
HR 0.98
p=0.8606
53. Durvalumab plus tremelimumab in NSCLC: phase 1b study
Antonia, S. Lancet Oncol 2016. Published Online February 5, 2016;
http://dx.doi.org/10.1016/S1470-2045(15)00544-6
Durvalumab: 3 mg/kg, 10 mg/kg, 15 mg/kg, or 20 mg/kg every 4 w, or 10 mg/kg every 2 w
Tremelimumab: 1, 3, or 10 mg/kg every 4 w for six doses then every 12 w for three doses
Durvalumab 10-20 mg/kg every 2 weeks or 4 weeks
plus tremelimumab 1 mg/kg (n=56)
Grado 1/2
%
Grado 3
%
Grado 4
%
Grado 5
%
Diarrea 17 7 0 0
Colitis 2 2 0 0
Enteritis 0 2 0 0
Prurito 20 0 0 0
Rash 11 0 0 0
Hipotiroidismo 7 2 0 0
Incremento amilasa 14 0 2 0
Incremento GPT/GOT 7/2 2/4 2/2 0
54. Durvalumab 10-20 mg/kg every 2 weeks or 4 weeks plus
tremelimumab 1 mg/kg
Todos los pacientes evaluables; %; n=52
Tasa de respuestas 23
Control de enfermedad 35
PD-L1-positivo (>25%); %; n=18
Tasa de respuestas 22
Control de enfermedad 33
PD-L1 negativo (<25%); %; n=28
Tasa de respuestas 29
Control de enfermedad 43
PD-L1 negativo (0%); %; n=20
Tasa de respuestas 40
Control de enfermedad 50
63. Grado
CTCAE
Tipo de
cuidado Corticoides
Otros
fármacos
inmunosupresores
Inmunoterapia:
actitud
posterior
1 Ambulatorio No recomendado No Continuar
2 Ambulatorio Cortic tópicos
Cort sistémicos:
0.5-1 mg/kg/d
No Suspender
temporalmente
(excepto
cutánea/endoc
rina)
3 Hospitalización Cort sistémicos
1-2 mg/kg/d x 3 d;
pauta descendente
Considerar si no se
resuelve tras 3-5 d
con corticoides
Suspender y
discutir
riesgo/benefici
o
4 Hospitalización;
Considerar UCI
Cortic iv: 6-MP
1-2 mg/kg/d x 3 d;
reducir
Considerar si no se
resuelve tras 3-5 d
con corticoides
Discontinuar
Infliximab si no mejoría en 3 días
66. McLaughlin J, Han G, Schalper KA, Carvajal-Hausdorf D, Pelakanou V, Rehman J, et al.
Quantitative Assessment of the Heterogeneity of PD-L1 Expression in Non–Small-Cell Lung
Cancer. JAMA Oncol. 2015 Nov 12;:1–9.
67. N=160
PD-L1: TC and IC
Overall discordance
rate:
48%
Ilie M, Ann Oncol. 2015 Oct 19;:mdv489–7.
Comparative study of the PD-L1 status between surgically resected
specimens and matched biopsies of NSCLC patients reveal major
discordances: a potential issue for anti-PD-L1 therapeutic strategies
68. En todos los casos
discordantes la
biopsia infravaloró
el resultado del
especimen
quirúrgico,
fundamentalmente
en células inmunes
Ilie M, Ann Oncol. 2015 Oct 19;:mdv489–7.
69. Eficacia y seguridad
Grado de innovación del fármaco
Necesidad no cubierta
Severidad de la enfermedad
Biomarcador eficiente y seguro
Coste
70.
71. Para concluir…
Inmunoterapia en cáncer de pulmón:
funciona
Cambio de estándar en segunda línea
Futuro: combinaciones
Múltiples checkpoints
Radioterapia
Quimioterapia
Necesitamos biomarcadores
Anti-PD1 vs Anti-PDL1??
Mecanismos de resistencia
74. Adaptación darwiniana del Oncólogo Médico
1960
Internista
1ª mutación +
1979
Quimioterapeuta
Vía muerta
75. Adaptación darwiniana del Oncólogo Médico
1960
Internista
1ª mutación +
2ª mutación +
1979
Quimioterapeuta
Vía muerta
1984
O. Médico
Oncólogo
insuficiente
76. Adaptación darwiniana del Oncólogo Médico
1960
Internista
1ª mutación +
2ª mutación +
3ª mutación +
1979
Quimioterapeuta
Vía muerta
1984
O. Médico
Oncólogo
insuficiente
2000
O. Médico
Molecular
Oncólogo
moderno
77. Adaptación darwiniana del Oncólogo Médico
1960
Internista
1ª mutación +
2ª mutación +
3ª mutación +
4ª mutación +
1979
Quimioterapeuta
Vía muerta
1984
O. Médico
Oncólogo
insuficiente
2000
O. Médico
Molecular
Oncólogo
moderno
2010
O. Médico
Molecular
Inmunólogo
Oncólogo
del futuro
78. No hay una clara asociación entre la expresión de PD-
L1 y la histología del CP
100
80
60
40
20
0
Non-squamous
14/30 (47%)
Squamous
11/29 (38%)
PD-L1 IHC
5% cut-off
NSCLC histology
PD–L1tumor
membranestaining(%)
PD-L1–positive
PD-L1–negative
Harbison CT, et al. Poster presented at ELCC 2014 (Abstract 102P).
79. In a meta-analysis, PD-L1 expression by IHC was related to worse prognosis (HR=1.72; 95% CI: 1.32–2.24)
• PD-L1 positivity by QIF alone could not show any predictive value
Study or
subgroup
log [hazard
ratio] SE Weight
Hazard ratio
IV, fixed, 95%
CI Year
Hazard ratio
IV, fixed, 95% CI
8.1.1 IHC
Mu 2011
Ma 2011
Chen YB 2012
Azuma 2014
Zhang 2014
Yang 2014
Subtotal (95%CI)
0.65
0.19
1.02
0.2
0.5
0.09
0.28
0.89
0.26
0.22
0.53
0.73
15.3%
1.5%
17.7%
24.7%
4.3%
2.2%
65.7%
1.92 [1.11, 3.32]
1.21 [0.21, 6.92]
2.77 [1.67, 4.62]
1.22 [0.79, 1.88]
1.65 [0.58, 4.66]
1.09 [0.26, 4.58]
1.72 [1.32, 2.24]
2011
2011
2012
2014
2014
2014
Heterogeneity: Chi2 = 6.49, df = 5 (P = 0.26); I2 = 23%
Test for overall effect: Z = 4.01 (P < 0.0001)
8.1.2 QIF
Velcheti (US) 2014
Velcheti (Greece) 2014
Subtotal (95% CI)
–0.23
0.26
0.32
0.23
11.7%
22.6%
34.3%
0.79 [0.42, 1.49]
1.30 [0.83, 2.04]
1.10 [0.76, 1.58]
2014
2014
Heterogeneity: Chi2 = 1.55, df = 1 (P = 0.21); I2 = 35%
Test for overall effect: Z = 0.50 (P = 0.62)
Total (95% CI)
Heterogeneity: Chi2 = 11.81, df = 7 (P = 0.11); I2 = 41%
Test for overall effect: Z = 3.54 (P = 0.0004)
Test for subgroup differences: Chi2 = 3.78, df = 1 (P = 0.05); I2 = 73.5%
100.0%
1.47 (1.19,
1.83)
PD-L1 expression may be predictive of worse prognosis
QIF = quantitative immunofluorescence.
Pan ZK, et al. J Thorac Dis. 2015;7(3):462-470.
0.1 0.2 0.5 1 2 5 10
Favors (PD-L1–) Favors (PD-L1+)
80. Pembro
10 mg/kg
Q3W
Nonrandomized
(N = 38)
• PD-L1+ or PD-L1–
tumors
• ≥2 previous
therapies
Randomized
(N = 280)
• PD-L1+ tumors
• ≥1 previous
therapy
Pembro
10 mg/kg
Q3W
Pembro
10 mg/kg
Q2W
R
(3:2)
Pembro
10 mg/kg
Q2W
Nonrandomized
(N = 43)
• PD-L1– tumors
• ≥1 previous
therapies
Pembro
10 mg/kg
Q3W
Nonrandomized
(N = 33)
• PD-L1+ tumors
• ≥2 previous
therapies
Pembro
2 mg/kg
Q3W
Nonrandomized
(N = 55)
• PD-L1+ tumors
• ≥1 previous
therapies
• Patients with tumors of any histology eligible
• Treatment continued until confirmed disease progression, intolerable toxicity, or other reason
• Response assessed every 9 weeks per RECIST v1.1 per central reviewa
• PD-L1 assessment1
• Enrollment: Prototype assay using the Merck 22C3 antibody
• Relationship with efficacy: Dako PD-L1 IHC 22C3 pharmDx™ Assay
aTreatment decisions were managed per irRC by investigator review.
1. Garon EB et al. N Engl J Med. 2015;372:2018-20.
Soria et al. Ann Oncol 2015; 26 (suppl 6): abstr 33LBA
Efficacy and Safety of Pembrolizumab (MK-3475) for Patients With Previously
Treated Advanced NSCLC Enrolled in KEYNOTE-001