Brentuximab is approved for first line treatment of Hodgkin lymphoma and peripheral T-cell lymphoma based on pivotal studies showing improved progression-free survival compared to physician's choice. Brigatinib is approved for NSCLC previously treated with crizotinib based on a trial showing improved progression-free survival compared to placebo. Lenvatinib is approved as first line treatment for unresectable hepatocellular carcinoma based on a trial showing non-inferior overall survival and improved progression-free survival compared to sorafenib. Osimertinib is approved as first line treatment for EGFR mutant NSCLC based on a trial showing improved progression-free survival compared to first generation EGFR TKIs.
El futuro del tratamiento del cáncer renal metastásico: inmunoterapia y terap...Mauricio Lema
Ponencia en el primer simposio de la Asociación Colombiana de Hematología y Oncología (ACHO) de cáncer genitourinario, Bogotá, septiembre 23 y 24 de 2016.
Renal Cell Carcinoma Diagnosis And ManagementRHMBONCO
This document provides an overview of renal cell carcinoma (RCC), including its epidemiology, pathology, clinical presentation, evaluation and staging, prognosis, and treatment options. RCC incidence has been rising and is more common in men than women. Surgery is the main treatment for localized RCC, while targeted therapies like sorafenib and sunitinib have improved outcomes for metastatic RCC compared to previous chemotherapy options. Ongoing clinical trials are exploring adjuvant and neoadjuvant therapies to improve prognosis.
Radiotherapy and Cetuximab in head and neck cancer.pptxNamrata Das
1. The document discusses several trials evaluating the addition of cetuximab, an EGFR inhibitor, to radiotherapy or chemoradiotherapy for squamous cell carcinoma of the head and neck.
2. The landmark Bonner trial showed improved locoregional control and overall survival when cetuximab was added to radiotherapy alone.
3. Subsequent trials like RTOG 0522 and TREMPLIN found no additional benefit when cetuximab was added to chemoradiotherapy, with increased toxicity.
4. For HPV-positive oropharyngeal cancer, trials like RTOG 1016, De-ESCALATE and TROG 12.01 found replacement
This document discusses targeted therapy for breast cancer. It begins by providing background on declining mortality rates for breast cancer over time. It then discusses how cancers develop multiple alterations that allow uncontrolled growth and outlines six essential alterations in cell physiology that contribute to malignancy. The document discusses molecular alterations that occur in breast cancer progression. It defines targeted therapy as drugs that target uniquely disrupted pathways in cancer cells. The document outlines several targeted therapies for breast cancer including hormonal therapies like tamoxifen, aromatase inhibitors, and fulvestrant. It discusses clinical trials demonstrating the benefits of these therapies. It also discusses therapies that target the HER2 receptor like trastuzumab and lapatinib. In summary, the document provides an overview of targeted
Recent advancements in metastatic colorectal cancer treatmentKindai University
In this presentation, the presenter tries to provide an overview of the current established treatment strategies, based on their clinical outcomes as well as their mechanisms, limitations that remain to be overcome, and their future applicability for the treatment of human Colorectal Cancer.
This document provides information on the treatment of metastatic renal cell carcinoma. It discusses current targeted therapies for RCC including inhibitors of VEGF and mTOR pathways such as sunitinib, sorafenib, everolimus and temsirolimus. Patient outcomes with various first and second line targeted therapies are presented. Guidelines for cytoreductive nephrectomy and metastasectomy are also summarized.
- The document summarizes a clinical trial that compared cisplatin chemotherapy plus radiotherapy (standard treatment) to cetuximab (EGFR inhibitor) plus radiotherapy for low-risk HPV-positive oropharyngeal cancer.
- The trial found that using cetuximab instead of cisplatin resulted in no reduction in toxicity but significantly worse tumor control outcomes, including lower 2-year overall survival and higher recurrence rates.
- The results suggest that cisplatin remains the standard of care for concurrent chemotherapy with radiotherapy for HPV-positive oropharyngeal cancer and that treatment de-escalation strategies removing systemic chemotherapy need caution.
This document summarizes the management of urinary bladder cancer. It discusses staging, histopathologic types, and treatment options for non-muscle invasive and muscle invasive bladder cancer as well as metastatic disease. Standard first-line chemotherapy for metastatic bladder cancer includes gemcitabine and cisplatin or MVAC. Newer chemotherapy regimens and agents are also discussed.
El futuro del tratamiento del cáncer renal metastásico: inmunoterapia y terap...Mauricio Lema
Ponencia en el primer simposio de la Asociación Colombiana de Hematología y Oncología (ACHO) de cáncer genitourinario, Bogotá, septiembre 23 y 24 de 2016.
Renal Cell Carcinoma Diagnosis And ManagementRHMBONCO
This document provides an overview of renal cell carcinoma (RCC), including its epidemiology, pathology, clinical presentation, evaluation and staging, prognosis, and treatment options. RCC incidence has been rising and is more common in men than women. Surgery is the main treatment for localized RCC, while targeted therapies like sorafenib and sunitinib have improved outcomes for metastatic RCC compared to previous chemotherapy options. Ongoing clinical trials are exploring adjuvant and neoadjuvant therapies to improve prognosis.
Radiotherapy and Cetuximab in head and neck cancer.pptxNamrata Das
1. The document discusses several trials evaluating the addition of cetuximab, an EGFR inhibitor, to radiotherapy or chemoradiotherapy for squamous cell carcinoma of the head and neck.
2. The landmark Bonner trial showed improved locoregional control and overall survival when cetuximab was added to radiotherapy alone.
3. Subsequent trials like RTOG 0522 and TREMPLIN found no additional benefit when cetuximab was added to chemoradiotherapy, with increased toxicity.
4. For HPV-positive oropharyngeal cancer, trials like RTOG 1016, De-ESCALATE and TROG 12.01 found replacement
This document discusses targeted therapy for breast cancer. It begins by providing background on declining mortality rates for breast cancer over time. It then discusses how cancers develop multiple alterations that allow uncontrolled growth and outlines six essential alterations in cell physiology that contribute to malignancy. The document discusses molecular alterations that occur in breast cancer progression. It defines targeted therapy as drugs that target uniquely disrupted pathways in cancer cells. The document outlines several targeted therapies for breast cancer including hormonal therapies like tamoxifen, aromatase inhibitors, and fulvestrant. It discusses clinical trials demonstrating the benefits of these therapies. It also discusses therapies that target the HER2 receptor like trastuzumab and lapatinib. In summary, the document provides an overview of targeted
Recent advancements in metastatic colorectal cancer treatmentKindai University
In this presentation, the presenter tries to provide an overview of the current established treatment strategies, based on their clinical outcomes as well as their mechanisms, limitations that remain to be overcome, and their future applicability for the treatment of human Colorectal Cancer.
This document provides information on the treatment of metastatic renal cell carcinoma. It discusses current targeted therapies for RCC including inhibitors of VEGF and mTOR pathways such as sunitinib, sorafenib, everolimus and temsirolimus. Patient outcomes with various first and second line targeted therapies are presented. Guidelines for cytoreductive nephrectomy and metastasectomy are also summarized.
- The document summarizes a clinical trial that compared cisplatin chemotherapy plus radiotherapy (standard treatment) to cetuximab (EGFR inhibitor) plus radiotherapy for low-risk HPV-positive oropharyngeal cancer.
- The trial found that using cetuximab instead of cisplatin resulted in no reduction in toxicity but significantly worse tumor control outcomes, including lower 2-year overall survival and higher recurrence rates.
- The results suggest that cisplatin remains the standard of care for concurrent chemotherapy with radiotherapy for HPV-positive oropharyngeal cancer and that treatment de-escalation strategies removing systemic chemotherapy need caution.
This document summarizes the management of urinary bladder cancer. It discusses staging, histopathologic types, and treatment options for non-muscle invasive and muscle invasive bladder cancer as well as metastatic disease. Standard first-line chemotherapy for metastatic bladder cancer includes gemcitabine and cisplatin or MVAC. Newer chemotherapy regimens and agents are also discussed.
This document discusses treatment de-escalation strategies for HPV-positive oropharyngeal cancer. It provides details on the natural history of HPV and its life cycles. It also summarizes several clinical trials that aimed to de-escalate treatment intensity through strategies like reduced radiation doses, substituting chemotherapy agents, and limiting treatment volumes. One study found that substituting cetuximab for cisplatin reduced survival rates. Another trial found that induction chemotherapy followed by reduced radiation if patients responded well was feasible but came with increased toxicity. A third study found that transoral surgery followed by hyperfractionated radiotherapy with docetaxel achieved high rates of local control and survival with acceptable toxicity levels.
This document discusses the use of neoadjuvant therapy for renal cell carcinoma (RCC). It notes that RCC accounts for about 2-3% of adult cancers. While nephrectomy is standard for localized RCC, 30-40% of patients experience recurrence. Neoadjuvant targeted therapy or immunotherapy offers potential advantages of tumor shrinkage prior to surgery or enabling surgery for otherwise unresectable tumors. Several studies found tyrosine kinase inhibitors like sunitinib, pazopanib, and axitinib shrank tumors in 80-90% of patients, facilitated resection, and allowed partial nephrectomies. Ongoing clinical trials are further evaluating neoadjuvant therapy to
6- mshabeb asiri - is extended field concurrent chemoradiation an option forBasalama Ali
This study compared extended field concurrent chemoradiation (EF-CCRT) to whole pelvis CCRT (WP-CCRT) in patients with locally advanced cervical cancer and enlarged pelvic nodes but radiologically negative para-aortic lymph nodes. EF-CCRT resulted in significantly fewer para-aortic failures compared to WP-CCRT with similar toxicity profiles. While EF-CCRT showed promising results with improved para-aortic control, the study was limited by its small sample size and lack of PET staging. Larger multicenter trials are needed to validate whether EF-CCRT outcomes are superior to WP-CCRT.
Colorectal Cancer Research & Treatment News - recap from the May 2014 ASCO co...Fight Colorectal Cancer
This document summarizes key findings from the PRIME trial evaluating the addition of panitumumab to FOLFOX4 as first-line treatment for metastatic colorectal cancer. Biomarker analysis found that KRAS exon 2 wild-type tumors derived greater benefit from the addition of panitumumab, with a progression-free survival advantage compared to FOLFOX4 alone. Further biomarker testing found mutations in other RAS isoforms or BRAF reduced likelihood of benefit from panitumumab. The results support use of RAS/BRAF mutation testing to select patients for first-line anti-EGFR therapy in combination with chemotherapy.
The document summarizes strategies for therapeutic intervention in hepatocellular carcinoma (HCC). It discusses using tumor biology to individualize treatment, developing multimodality algorithms incorporating molecular targets, and novel locoregional therapies. It also describes integrating divisions for transplantation, hepatology, and research at the Montefiore Einstein Liver Center to provide a coordinated approach to HCC care and trials of therapies like sorafenib.
The document summarizes strategies for therapeutic intervention in hepatocellular carcinoma (HCC). It discusses using tumor biology to individualize treatment, developing multimodality algorithms incorporating molecular targets, and novel locoregional therapies. It also describes integrating divisions for transplantation, hepatology, and research at the Montefiore Einstein Liver Center to provide a coordinated approach to HCC care and trials of therapies like sorafenib.
This document discusses the management of triple negative breast cancer (TNBC). It begins with an overview of the three main subtypes of breast cancer and their associated treatments. It then focuses on the characteristics and treatment challenges of TNBC, including its aggressiveness, younger patient population, and lack of targeted therapies. Current treatment options for metastatic TNBC are discussed, including various chemotherapy regimens. The document also touches on neoadjuvant and adjuvant systemic therapy approaches as well as ongoing research into better understanding the biology of TNBC to revolutionize outcomes.
Hitting the Target in HER2-Positive Metastatic Colorectal Canceri3 Health
i3 Health is pleased to make the speaker slides from this activity available for use as a non-accredited self-study or teaching resource.
This slide deck will share the latest data and strategies for hitting the target in HER2-positive metastatic colorectal cancer. Dr. Christopher Lieu, Associate Professor at the University of Colorado Cancer Center, explores actionable targets to inform personalized care plans, guideline-recommended combination and sequencing strategies, adverse event monitoring and management, and more.
STATEMENT OF NEED
An estimated 153,020 new cases of colorectal cancer (CRC) are diagnosed annually, and 52,550 people die of the disease (Siegel et al, 2023). Approximately 22% of patients present with metastatic disease, which is associated with a dismal 5-year survival rate of 15% (SEER, 2022). Targeting biomarkers is a key strategy for expanding therapeutic options and improving outcomes in metastatic CRC. Human epidermal growth factor receptor 2 (HER2) amplification status and treatments targeting HER2 are some of the most recent additions to the arsenal of targeted therapy for this disease. This activity chaired by Christopher Lieu, MD, Associate Director of Clinical Research at the University of Colorado Cancer Center, will provide expert perspectives and practical guidance on treating HER2-positive metastatic CRC.
TARGET AUDIENCE
Oncologists, gastroenterologists, nurse practitioners, physician assistants, oncology nurses, and other health care professionals involved in the treatment of patients with colorectal cancer (CRC).
LEARNING OBJECTIVES
Upon completion of this activity, participants should be able to
Distinguish actionable targets that can inform personalized care plans in metastatic CRC
Evaluate practice guidelines on treatment combinations and sequences for patients with metastatic CRC
Appraise emerging efficacy and safety data on novel targeted therapies for patients with HER2-positive metastatic CRC
Assess strategies for optimizing the safety and tolerability of novel targeted therapies for HER2-positive metastatic CRC
This document summarizes a presentation on the management of metastatic colorectal cancer (mCRC) in 2017. It discusses several key points:
1) Patient stratification is important in determining treatment approach for mCRC, taking into account factors like disease extent and symptoms.
2) A multidisciplinary team approach is mandatory for developing optimal treatment plans.
3) Assessment of predictive biomarkers like RAS mutations helps determine which first-line treatments may be most effective.
4) Tumor location (right vs left-sided colon cancer) can impact treatment outcomes and response to certain drugs like anti-EGFR therapies.
5) Multiple clinical trials over time have led to improved survival outcomes and more
- Metastatic breast cancer is commonly diagnosed in elderly patients, with around 40% of cases occurring in patients over 65 years old.
- Treatment of metastatic breast cancer in elderly patients focuses on prolonging life and controlling symptoms while maintaining quality of life and minimizing toxicity.
- For hormone receptor-positive cancer, hormone therapy is usually the initial treatment, with chemotherapy considered for hormone-refractory disease while choosing less toxic options. Clinical trials have also shown benefit from hormone withdrawal in some cases.
This document discusses pancreatic cancer, including risk factors, symptoms, diagnosis, staging, treatment options and clinical trials. It summarizes a case study of a 65-year-old woman with unresectable pancreatic cancer. Key points are that pancreatic cancer has a poor prognosis, surgery is rarely curative, and a multidisciplinary approach including chemotherapy may help control symptoms and prolong survival for advanced disease. Gemcitabine is established as the standard adjuvant chemotherapy based on positive randomized controlled 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 immunotherapies for hepatocellular carcinoma (HCC). It begins by explaining that HCC typically develops in the context of chronic liver disease and cirrhosis. For early-stage HCC, surgical resection and liver transplantation can be curative, while radiofrequency ablation and transarterial chemoembolization are common local therapies for intermediate-stage HCC. Systemic therapies were historically ineffective for advanced HCC, but tyrosine kinase inhibitors like sorafenib were found to provide a survival benefit. More recent immunotherapies like nivolumab, pembrolizumab, and combinations with ipilimumab have shown response rates of 15-31% in advanced HCC
Larry W. Kwak discusses ongoing research for targeted therapy of Hodgkin's lymphoma. The goals are to [1] improve remission rates and decrease risk of death, [2] minimize side effects and maintain or prolong remissions, and [3] develop additional options for relapsed or refractory disease. Research is exploring targeted agents like HDAC inhibitors, OX40 receptor ligation, and oral panobinostat to alter the tumor microenvironment and induce apoptosis. Brentuximab vedotin, an anti-CD30 antibody-drug conjugate, has shown durable responses in refractory Hodgkin's lymphoma with manageable toxicity. Introduction of targeted therapies into frontline treatment, such as brentuxim
Larry W. Kwak discusses ongoing research goals and therapeutic options for Hodgkin's lymphoma, including improving remission rates and minimizing side effects. He describes targeted therapies under investigation, such as deacetylase inhibitors that induce cell cycle arrest and apoptosis as well as alter the tumor microenvironment. Kwak also discusses the use of oral HDAC inhibitors like mocetinostat, which have shown clinical activity in Hodgkin's lymphoma. Finally, he examines the efficacy of the antibody-drug conjugate brentuximab vedotin in treating relapsed and refractory Hodgkin's lymphoma.
This case study examines the use of cetuximab-based chemotherapy for the re-treatment of patients with metastatic colorectal cancer who had previously responded to cetuximab treatment but experienced disease progression after stopping treatment. The study aims to evaluate the overall response and safety of re-treating these patients with cetuximab-containing chemotherapy. It describes the study design, inclusion/exclusion criteria, experimental and control treatments, and primary/secondary outcome measures that will be assessed over a 2-year period.
This document summarizes recent developments in the treatment of head and neck cancer, focusing on the humanized monoclonal antibody nimotuzumab. A phase IIb clinical trial found that combining nimotuzumab with chemoradiation therapy significantly improved overall survival rates compared to chemoradiation alone. Specifically, the 5-year overall survival rate was 57% for patients receiving chemoradiation plus nimotuzumab, compared to only 26% for those receiving chemoradiation alone. Overall, the study demonstrates that nimotuzumab can be safely and effectively administered along with radiation therapy or chemoradiation therapy for advanced head and neck cancer.
Local Advanced Lung Cancer: Artificial Intelligence, Synergetics, Complex Sys...Oleg Kshivets
Overall life span (LS) was 1671.7±1721.6 days and cumulative 5YS reached 62.4%, 10 years – 50.4%, 20 years – 44.6%. 94 LCP lived more than 5 years without cancer (LS=2958.6±1723.6 days), 22 – more than 10 years (LS=5571±1841.8 days). 67 LCP died because of LC (LS=471.9±344 days). AT significantly improved 5YS (68% vs. 53.7%) (P=0.028 by log-rank test). Cox modeling displayed that 5YS of LCP significantly depended on: N0-N12, T3-4, blood cell circuit, cell ratio factors (ratio between cancer cells-CC and blood cells subpopulations), LC cell dynamics, recalcification time, heparin tolerance, prothrombin index, protein, AT, procedure type (P=0.000-0.031). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and N0-12 (rank=1), thrombocytes/CC (rank=2), segmented neutrophils/CC (3), eosinophils/CC (4), erythrocytes/CC (5), healthy cells/CC (6), lymphocytes/CC (7), stick neutrophils/CC (8), leucocytes/CC (9), monocytes/CC (10). Correct prediction of 5YS was 100% by neural networks computing (error=0.000; area under ROC curve=1.0).
This document discusses treatment de-escalation strategies for HPV-positive oropharyngeal cancer. It provides details on the natural history of HPV and its life cycles. It also summarizes several clinical trials that aimed to de-escalate treatment intensity through strategies like reduced radiation doses, substituting chemotherapy agents, and limiting treatment volumes. One study found that substituting cetuximab for cisplatin reduced survival rates. Another trial found that induction chemotherapy followed by reduced radiation if patients responded well was feasible but came with increased toxicity. A third study found that transoral surgery followed by hyperfractionated radiotherapy with docetaxel achieved high rates of local control and survival with acceptable toxicity levels.
This document discusses the use of neoadjuvant therapy for renal cell carcinoma (RCC). It notes that RCC accounts for about 2-3% of adult cancers. While nephrectomy is standard for localized RCC, 30-40% of patients experience recurrence. Neoadjuvant targeted therapy or immunotherapy offers potential advantages of tumor shrinkage prior to surgery or enabling surgery for otherwise unresectable tumors. Several studies found tyrosine kinase inhibitors like sunitinib, pazopanib, and axitinib shrank tumors in 80-90% of patients, facilitated resection, and allowed partial nephrectomies. Ongoing clinical trials are further evaluating neoadjuvant therapy to
6- mshabeb asiri - is extended field concurrent chemoradiation an option forBasalama Ali
This study compared extended field concurrent chemoradiation (EF-CCRT) to whole pelvis CCRT (WP-CCRT) in patients with locally advanced cervical cancer and enlarged pelvic nodes but radiologically negative para-aortic lymph nodes. EF-CCRT resulted in significantly fewer para-aortic failures compared to WP-CCRT with similar toxicity profiles. While EF-CCRT showed promising results with improved para-aortic control, the study was limited by its small sample size and lack of PET staging. Larger multicenter trials are needed to validate whether EF-CCRT outcomes are superior to WP-CCRT.
Colorectal Cancer Research & Treatment News - recap from the May 2014 ASCO co...Fight Colorectal Cancer
This document summarizes key findings from the PRIME trial evaluating the addition of panitumumab to FOLFOX4 as first-line treatment for metastatic colorectal cancer. Biomarker analysis found that KRAS exon 2 wild-type tumors derived greater benefit from the addition of panitumumab, with a progression-free survival advantage compared to FOLFOX4 alone. Further biomarker testing found mutations in other RAS isoforms or BRAF reduced likelihood of benefit from panitumumab. The results support use of RAS/BRAF mutation testing to select patients for first-line anti-EGFR therapy in combination with chemotherapy.
The document summarizes strategies for therapeutic intervention in hepatocellular carcinoma (HCC). It discusses using tumor biology to individualize treatment, developing multimodality algorithms incorporating molecular targets, and novel locoregional therapies. It also describes integrating divisions for transplantation, hepatology, and research at the Montefiore Einstein Liver Center to provide a coordinated approach to HCC care and trials of therapies like sorafenib.
The document summarizes strategies for therapeutic intervention in hepatocellular carcinoma (HCC). It discusses using tumor biology to individualize treatment, developing multimodality algorithms incorporating molecular targets, and novel locoregional therapies. It also describes integrating divisions for transplantation, hepatology, and research at the Montefiore Einstein Liver Center to provide a coordinated approach to HCC care and trials of therapies like sorafenib.
This document discusses the management of triple negative breast cancer (TNBC). It begins with an overview of the three main subtypes of breast cancer and their associated treatments. It then focuses on the characteristics and treatment challenges of TNBC, including its aggressiveness, younger patient population, and lack of targeted therapies. Current treatment options for metastatic TNBC are discussed, including various chemotherapy regimens. The document also touches on neoadjuvant and adjuvant systemic therapy approaches as well as ongoing research into better understanding the biology of TNBC to revolutionize outcomes.
Hitting the Target in HER2-Positive Metastatic Colorectal Canceri3 Health
i3 Health is pleased to make the speaker slides from this activity available for use as a non-accredited self-study or teaching resource.
This slide deck will share the latest data and strategies for hitting the target in HER2-positive metastatic colorectal cancer. Dr. Christopher Lieu, Associate Professor at the University of Colorado Cancer Center, explores actionable targets to inform personalized care plans, guideline-recommended combination and sequencing strategies, adverse event monitoring and management, and more.
STATEMENT OF NEED
An estimated 153,020 new cases of colorectal cancer (CRC) are diagnosed annually, and 52,550 people die of the disease (Siegel et al, 2023). Approximately 22% of patients present with metastatic disease, which is associated with a dismal 5-year survival rate of 15% (SEER, 2022). Targeting biomarkers is a key strategy for expanding therapeutic options and improving outcomes in metastatic CRC. Human epidermal growth factor receptor 2 (HER2) amplification status and treatments targeting HER2 are some of the most recent additions to the arsenal of targeted therapy for this disease. This activity chaired by Christopher Lieu, MD, Associate Director of Clinical Research at the University of Colorado Cancer Center, will provide expert perspectives and practical guidance on treating HER2-positive metastatic CRC.
TARGET AUDIENCE
Oncologists, gastroenterologists, nurse practitioners, physician assistants, oncology nurses, and other health care professionals involved in the treatment of patients with colorectal cancer (CRC).
LEARNING OBJECTIVES
Upon completion of this activity, participants should be able to
Distinguish actionable targets that can inform personalized care plans in metastatic CRC
Evaluate practice guidelines on treatment combinations and sequences for patients with metastatic CRC
Appraise emerging efficacy and safety data on novel targeted therapies for patients with HER2-positive metastatic CRC
Assess strategies for optimizing the safety and tolerability of novel targeted therapies for HER2-positive metastatic CRC
This document summarizes a presentation on the management of metastatic colorectal cancer (mCRC) in 2017. It discusses several key points:
1) Patient stratification is important in determining treatment approach for mCRC, taking into account factors like disease extent and symptoms.
2) A multidisciplinary team approach is mandatory for developing optimal treatment plans.
3) Assessment of predictive biomarkers like RAS mutations helps determine which first-line treatments may be most effective.
4) Tumor location (right vs left-sided colon cancer) can impact treatment outcomes and response to certain drugs like anti-EGFR therapies.
5) Multiple clinical trials over time have led to improved survival outcomes and more
- Metastatic breast cancer is commonly diagnosed in elderly patients, with around 40% of cases occurring in patients over 65 years old.
- Treatment of metastatic breast cancer in elderly patients focuses on prolonging life and controlling symptoms while maintaining quality of life and minimizing toxicity.
- For hormone receptor-positive cancer, hormone therapy is usually the initial treatment, with chemotherapy considered for hormone-refractory disease while choosing less toxic options. Clinical trials have also shown benefit from hormone withdrawal in some cases.
This document discusses pancreatic cancer, including risk factors, symptoms, diagnosis, staging, treatment options and clinical trials. It summarizes a case study of a 65-year-old woman with unresectable pancreatic cancer. Key points are that pancreatic cancer has a poor prognosis, surgery is rarely curative, and a multidisciplinary approach including chemotherapy may help control symptoms and prolong survival for advanced disease. Gemcitabine is established as the standard adjuvant chemotherapy based on positive randomized controlled 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 immunotherapies for hepatocellular carcinoma (HCC). It begins by explaining that HCC typically develops in the context of chronic liver disease and cirrhosis. For early-stage HCC, surgical resection and liver transplantation can be curative, while radiofrequency ablation and transarterial chemoembolization are common local therapies for intermediate-stage HCC. Systemic therapies were historically ineffective for advanced HCC, but tyrosine kinase inhibitors like sorafenib were found to provide a survival benefit. More recent immunotherapies like nivolumab, pembrolizumab, and combinations with ipilimumab have shown response rates of 15-31% in advanced HCC
Larry W. Kwak discusses ongoing research for targeted therapy of Hodgkin's lymphoma. The goals are to [1] improve remission rates and decrease risk of death, [2] minimize side effects and maintain or prolong remissions, and [3] develop additional options for relapsed or refractory disease. Research is exploring targeted agents like HDAC inhibitors, OX40 receptor ligation, and oral panobinostat to alter the tumor microenvironment and induce apoptosis. Brentuximab vedotin, an anti-CD30 antibody-drug conjugate, has shown durable responses in refractory Hodgkin's lymphoma with manageable toxicity. Introduction of targeted therapies into frontline treatment, such as brentuxim
Larry W. Kwak discusses ongoing research goals and therapeutic options for Hodgkin's lymphoma, including improving remission rates and minimizing side effects. He describes targeted therapies under investigation, such as deacetylase inhibitors that induce cell cycle arrest and apoptosis as well as alter the tumor microenvironment. Kwak also discusses the use of oral HDAC inhibitors like mocetinostat, which have shown clinical activity in Hodgkin's lymphoma. Finally, he examines the efficacy of the antibody-drug conjugate brentuximab vedotin in treating relapsed and refractory Hodgkin's lymphoma.
This case study examines the use of cetuximab-based chemotherapy for the re-treatment of patients with metastatic colorectal cancer who had previously responded to cetuximab treatment but experienced disease progression after stopping treatment. The study aims to evaluate the overall response and safety of re-treating these patients with cetuximab-containing chemotherapy. It describes the study design, inclusion/exclusion criteria, experimental and control treatments, and primary/secondary outcome measures that will be assessed over a 2-year period.
This document summarizes recent developments in the treatment of head and neck cancer, focusing on the humanized monoclonal antibody nimotuzumab. A phase IIb clinical trial found that combining nimotuzumab with chemoradiation therapy significantly improved overall survival rates compared to chemoradiation alone. Specifically, the 5-year overall survival rate was 57% for patients receiving chemoradiation plus nimotuzumab, compared to only 26% for those receiving chemoradiation alone. Overall, the study demonstrates that nimotuzumab can be safely and effectively administered along with radiation therapy or chemoradiation therapy for advanced head and neck cancer.
Local Advanced Lung Cancer: Artificial Intelligence, Synergetics, Complex Sys...Oleg Kshivets
Overall life span (LS) was 1671.7±1721.6 days and cumulative 5YS reached 62.4%, 10 years – 50.4%, 20 years – 44.6%. 94 LCP lived more than 5 years without cancer (LS=2958.6±1723.6 days), 22 – more than 10 years (LS=5571±1841.8 days). 67 LCP died because of LC (LS=471.9±344 days). AT significantly improved 5YS (68% vs. 53.7%) (P=0.028 by log-rank test). Cox modeling displayed that 5YS of LCP significantly depended on: N0-N12, T3-4, blood cell circuit, cell ratio factors (ratio between cancer cells-CC and blood cells subpopulations), LC cell dynamics, recalcification time, heparin tolerance, prothrombin index, protein, AT, procedure type (P=0.000-0.031). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and N0-12 (rank=1), thrombocytes/CC (rank=2), segmented neutrophils/CC (3), eosinophils/CC (4), erythrocytes/CC (5), healthy cells/CC (6), lymphocytes/CC (7), stick neutrophils/CC (8), leucocytes/CC (9), monocytes/CC (10). Correct prediction of 5YS was 100% by neural networks computing (error=0.000; area under ROC curve=1.0).
These lecture slides, by Dr Sidra Arshad, offer a quick overview of the physiological basis of a normal electrocardiogram.
Learning objectives:
1. Define an electrocardiogram (ECG) and electrocardiography
2. Describe how dipoles generated by the heart produce the waveforms of the ECG
3. Describe the components of a normal electrocardiogram of a typical bipolar lead (limb II)
4. Differentiate between intervals and segments
5. Enlist some common indications for obtaining an ECG
6. Describe the flow of current around the heart during the cardiac cycle
7. Discuss the placement and polarity of the leads of electrocardiograph
8. Describe the normal electrocardiograms recorded from the limb leads and explain the physiological basis of the different records that are obtained
9. Define mean electrical vector (axis) of the heart and give the normal range
10. Define the mean QRS vector
11. Describe the axes of leads (hexagonal reference system)
12. Comprehend the vectorial analysis of the normal ECG
13. Determine the mean electrical axis of the ventricular QRS and appreciate the mean axis deviation
14. Explain the concepts of current of injury, J point, and their significance
Study Resources:
1. Chapter 11, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 9, Human Physiology - From Cells to Systems, Lauralee Sherwood, 9th edition
3. Chapter 29, Ganong’s Review of Medical Physiology, 26th edition
4. Electrocardiogram, StatPearls - https://www.ncbi.nlm.nih.gov/books/NBK549803/
5. ECG in Medical Practice by ABM Abdullah, 4th edition
6. Chapter 3, Cardiology Explained, https://www.ncbi.nlm.nih.gov/books/NBK2214/
7. ECG Basics, http://www.nataliescasebook.com/tag/e-c-g-basics
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
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.
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Cell Therapy Expansion and Challenges in Autoimmune DiseaseHealth Advances
There is increasing confidence that cell therapies will soon play a role in the treatment of autoimmune disorders, but the extent of this impact remains to be seen. Early readouts on autologous CAR-Ts in lupus are encouraging, but manufacturing and cost limitations are likely to restrict access to highly refractory patients. Allogeneic CAR-Ts have the potential to broaden access to earlier lines of treatment due to their inherent cost benefits, however they will need to demonstrate comparable or improved efficacy to established modalities.
In addition to infrastructure and capacity constraints, CAR-Ts face a very different risk-benefit dynamic in autoimmune compared to oncology, highlighting the need for tolerable therapies with low adverse event risk. CAR-NK and Treg-based therapies are also being developed in certain autoimmune disorders and may demonstrate favorable safety profiles. Several novel non-cell therapies such as bispecific antibodies, nanobodies, and RNAi drugs, may also offer future alternative competitive solutions with variable value propositions.
Widespread adoption of cell therapies will not only require strong efficacy and safety data, but also adapted pricing and access strategies. At oncology-based price points, CAR-Ts are unlikely to achieve broad market access in autoimmune disorders, with eligible patient populations that are potentially orders of magnitude greater than the number of currently addressable cancer patients. Developers have made strides towards reducing cell therapy COGS while improving manufacturing efficiency, but payors will inevitably restrict access until more sustainable pricing is achieved.
Despite these headwinds, industry leaders and investors remain confident that cell therapies are poised to address significant unmet need in patients suffering from autoimmune disorders. However, the extent of this impact on the treatment landscape remains to be seen, as the industry rapidly approaches an inflection point.
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2. Outline
Brentuximab as first line for Hodgkin lymphoma; first line for peripheral T-cell
lymphoma
Brigatinib for NSCLC with positive ALK previously treated with crizotinib
Lenvatinib for unresectable NSCLC
Osimertinib as first line for locally advanced or metastatic NSCLC with positive EGFR
Eribulin for progressive locally advanced or metastatic breast cancer
3. Brentuximab as first line
for Hodgkin lymphoma;
first line for peripheral
T-cell lymphoma
4. Brentuximab
• Antibody Drug Conjugate (ADC) that delivers an antineoplastic agent that results in apoptotic cell
death selectively in CD30-expressing tumor cells
• Brand label : Adcetris
• Class of agents : antibody drug conjugate (ADC)
• Labeled indications
• Anaplastic large cell lymphoma (primary cutaneous), relapsed
• Anaplastic large cell lymphoma (systemic), previously untreated
• Anaplastic large cell lymphoma (systemic), relapsed
• Hodgkin lymphoma, previously untreated
• Hodgkin
5. Brentuximab
Recommended dosages
Previously untreated : 1.2 mg/kg (max 120
mg) every 2 weeks
Relapsed or refractory : 1.8 mg/kg (max 180
mg) every 3 weeks
Administration
Intravenous, each 50 mg vial with 10.5 sterile
water for injection resulting in a concentration of
5 mg/ml
Use within 24 hours of initial reconstitution
6. Approval of Use
US (FDA)
2011: relapse refractory Hodgkin
lymphoma, relapse refractory
systemic anaplastic large cell
lymphoma, maintenance for
Hodgkin lymphoma after ASCT
2017: relapse refractory cutaneous
T-cell lymphoma
2018: first line Hodgkin lymphoma,
first line peripheral T-cell
lymphoma
Europe (EMA)
2012: relapse refractory Hodgkin
lymphoma, relapse refractory
systemic anaplastic large cell
lymphoma, maintenance for
Hodgkin lymphoma after ASCT
2017: relapse refractory cutaneous
T-cell lymphoma
2018: first line Hodgkin lymphoma,
first line peripheral T-cell
lymphoma
Indonesia (BPOM)
2017: relapse refractory Hodgkin
lymphoma, relapse refractory
systemic anaplastic large cell
lymphoma
2019: relapse refractory cutaneous
T cell lymphoma
7.
8.
9.
10. Pivotal Studies (1)
No Studies Study
phase
Study design Result
1 SGN35-003
Subject:
Relapsed or refractory
Hodgkin lymphoma
after autologous stem-
cell transplantation
As:
Salvage, monotherapy
2 Multinational,
open-label
n=102
Progression-free survival
Brentuximab vedotin: 9.3 mo (95% CI 1.2-36.4)
Overall survival
Brentuximab vedotin: 40.5 mo (95% CI 28.7-not
estimable)
Duration of response
6.7 mo
CR: 34%
PR: 40%
Grade of recommendation: 2B
11. Pivotal Studies (2)
No Studies Study
phase
Study design Result
2 SGN35-004
Subject:
Relapsed or refractory
systemic anaplastic
large-cell lymphoma
As:
Salvage, monotherapy
2 Multinational,
open-label
n=58
Progression-free survival
Brentuximab vedotin: 13.3 mo (95% CI 6.9-NE)
Overall survival
Brentuximab vedotin: median not reached (95%CI
21.3-NE)
Duration of response
12.6 mo (95%CI 5.7 to NE)
CR: 57%
PR: 29%
Grade of recommendation: 2B
NE: not estimable
12. Pivotal Studies (3)
No Studies Study
phase
Study design Result
3 ALCANZA
Subject:
Relapsed or refractory
cutaneous T-cell
lymphoma
As:
First line
3 International,
open-label,
randomized,
multicentre
n=131
Progression-free survival (EMA criteria)
Brentuximab vedotin: 16.7 mo
Physician choice: 3.5 mo
HR 0.270 (95%CI 0.169-0.430; p<0.0001)
Progression-free survival (FDA criteria)
Brentuximab vedotin: 17.2 mo
Physician choice: 3.5 mo
HR 0.181 (95%CI 0.101-0.324; p<0.0001)
Response (ORR4)
Brentuximab vedotin: 56.3%
Physician choice: 12.5%
Grade of recommendation: 2C
NE: not estimable
ORR4: objective global response lasting at least 4 mo
13. Pivotal Studies (4)
No Studies Study
phase
Study design Result
4 AETHERA
Subject:
Unfavourable-risk
relapsed or primary
refractory classic
Hodgkin’s lymphoma
who had undergone
ASCT
As:
Salvage
3 Randomised,
double-blind,
placebo-
controlled
n=131
Hazard ratio
HR 0.57 (95%CI 0.40-0.81; p=0.0013)
Grade of recommendation: 3B
14. Brigatinib
• Brand label : Alunbrig
• Class of agents : targeted therapy, ALK inhibitor
• Labeled indications
• Non-small cell lung cancer, metastatic (ALK-positive)
• Dosage : 90 mg once daily for 7 days; if tolerated, increase dose to 180 mg once daily
• Off-label indications:
• Non-small cell lung cancer, advanced (initial ALK-inhibitor therapy)
• Dosage : 90
15. Briganitib
Recommended dosages
90 mg once daily for 7 days; if tolerated, increase
dose to 180 mg once daily
Administration
Oral, with or without fodd, swallow tablets
whole; do not crush or chew
16. Approval of Use
US (FDA)
April 28th, 2017: ALK+ NSCLC in
previously treated with crizotinib
Europe (EMA)
September 20th 2018: ALK+ NSCLC
in previously treated with crizotinib
Indonesia (BPOM)
On registration process
17.
18. Pivotal Studies (1)
No Studies Study
phase
Study design Result
1 ALTA Trial
Subject:
Non-small cell lung
cancer previously
treated with crizotinib
As:
Salvage
2 Open-label,
randomized,
multicenter,
international
n=222
Progression-free survival
Brigatinib: 16.7 mo (95% CI 1.2-36.4)
Overall survival
Brigatinib: not reached
22. • In 2018, international, multicentre, randomised, open-label, non-inferiority trial
(REFLECT) conducted in 954 patients with previously untreated, metastatic or
unresectable HCC.
• Patients were randomised (1:1) to receive lenvatinib (12 mg orally once daily for patients
with a baseline body weight of ≥60 kg and 8 mg orally once daily for patients with a
baseline body weight of <60 kg) or sorafenib (400 mg orally twice daily).
23. RESULTS
• REFLECT demonstrated that lenvatinib was
non-inferior but not statistically superior to
sorafenib for overall survival (OS) (HR 0.92;
95% CI: 0.79, 1.06).
• Median OS in the lenvatinib arm was 13.6
months and 12.3 months in the sorafenib
arm.
• REFLECT also demonstrated a statistically
significant improvement in progression-free
survival (PFS) with lenvatinib as compared to
sorafenib.
• Median PFS was 7.3 months in the lenvatinib arm and 3.6
months in the sorafenib arm (HR 0.64; 95% CI: 0.55, 0.75;
p<0.001) per modified RECIST for HCC (mRECIST)
24. FDA Approval
• On August 16, 2018, lenvatinib (Lenvima) was approved for the first-
line treatment of patients with unresectable hepatocellular
carcinoma
• The recommended lenvatinib dosages for patients with HCC :
• 12 mg orally once daily in patients 60 kg or greater actual body weight or
• 8 mg orally once daily in patients less than 60 kg actual body weight.
ESMO 2018
25. Efek Samping
Hematologi (Jumlah %) Non Hematologi (Jumlah %)
Kenaikan bilirubin darah (15%) Hand and foot syndrome (27%)
Diare (39%)
Hipertensi (42%)
Penurunan nafsu makan (34%)
Penurunan berat badan (31%)
Lemas (30%)
Kerontokan rambut (3%)
Proteinuria (25%)
Gangguan suara (24%)
Mual (20%)
Nyeri abdomen (17%)
Peningkatan transaminase (14%)
Hipotiroid (14%)
Muntah (16%)
Konstipasi (16%)
Bercak merah (10%)
27. Osimertinib (Tagrisso)
•Osimertinib is a third generation, irreversible, oral EGFR-
TKI that inhibits both EGFR mutations and EGFR T790M
resistance mutations
•Osimertinib is a tyrosine kinase inhibitor, which acts by
blocking the activity of the epidermal growth factor
receptor (EGFR).
28. FDA Approval
• 2016: Osimertinib 2L for EGFR-TKI resistant disease for patients with
T790M mutation
• 2017: granted approval for 1st-line treatment of patients with
metastatic NSCLC whose tumours have EGFR mutations (exon 19
deletions or exon 21 L858R mutations); In 2018 osimertinib got full
approval
• 2018: Osimertinib as monotherapy for the 1st-line treatment of adult
patients with locally-advanced or metastatic NSCLC with activating
EGFR mutations
29. FLAURA Study
• FLAURA enrolled treatment naive patients aged ≥18 years (≥20 in
Japan) with Ex19del/L858R EGFR-mutated advanced NSCLC, and WHO
performance status 0–1; patients having stable CNS metastases that
did not require steroids for ≥2 weeks were allowed.
• 279 patients were treated with oral osimertinib at 80 mg once daily
and 277 patients received either gefitinib at 250 mg daily or erlotinib
150 mg orally per day.
30. FLAURA Study
• Survival data : the median overall survival with osimertinib
was 38.6 months versus 31.8 months with first generation
EGFR-TKIs, with a hazard ratio of 0.799 (p=0.0462).
• More than half (54%) of patients in the osimertinib group
were alive at three years compared to 44% in the standard
care group
a kinase inhibitor that inhibits the kinase activities of vascular endothelial growth factor (VEGF) receptors VEGFR1 (FLT1), VEGFR2 (KDR), and VEGFR3 (FLT4).
Lenvatinib inhibits other kinases that have been implicated in pathogenic angiogenesis, tumor growth, and cancer progression in addition to their normal cellular functions, including fibroblast growth factor (FGF) receptors FGFR1, 2, 3, and 4; platelet derived growth factor receptor alpha (PDGFRα), KIT, and RET.
also exhibits antiproliferative activity in hepatocellular carcinoma cell lines dependent on activated FGFR signaling with a concurrent inhibition of FGF-receptor substrate 2α phosphorylation.