1) The document discusses several studies presented at the ASCO 2020 conference regarding prostate cancer treatment updates. These include studies on chemo-hormonal therapy, androgen signaling inhibitors, and immunotherapy combinations.
2) A key study found that combining pembrolizumab and enzalutamide showed activity in patients with metastatic castration-resistant prostate cancer whose disease had progressed on enzalutamide, with an objective response rate of 12% and durable disease control.
3) Additional results from the conference included findings on predictive biomarkers, outcomes based on site of metastasis, and safety data from combination immunotherapy and targeted therapy trials for advanced prostate cancer.
- The addition of selective internal radiation therapy (SIRT) to sorafenib (SOR) did not significantly improve overall survival compared to SOR alone in patients with advanced hepatocellular carcinoma based on two randomized controlled trials.
- Subgroup analyses found potential clinical benefits for younger patients, those with non-alcoholic disease etiology, and those without cirrhosis.
- Regorafenib, a multi-kinase inhibitor, significantly improved progression-free survival, overall survival, and disease control compared to placebo in patients with hepatocellular carcinoma progressing on sorafenib.
- Lenvatinib, an oral multi-kinase inhibitor, demonstrated non-inferior
This document summarizes new adjuvant treatment strategies for early-stage HER2-positive breast cancer. It discusses trials showing improved disease-free survival when adding trastuzumab to chemotherapy as adjuvant therapy. More recent trials show additional benefits from combining trastuzumab with pertuzumab or using neratinib after initial trastuzumab therapy. The APHINITY trial found that adding pertuzumab to trastuzumab and chemotherapy significantly reduced the risk of invasive disease recurrence compared to placebo, trastuzumab and chemotherapy in the interim analysis. Benefits were greater in patients with node-positive disease or hormone receptor-negative breast cancer.
Optimal treatment sequence left side ras wt - case based (1)madurai
1. The document discusses optimal treatment sequence for left side RAS wild-type and BRAF wild-type metastatic colorectal cancer (mCRC).
2. It describes four groups of patients with metastatic disease based on resectability and provides treatment goals for each. Most patients initially present with unresectable disease.
3. Factors that influence first-line treatment choices for mCRC include biomarker status, tumor location, treatment sequence, and patient characteristics. Molecular testing for RAS and BRAF is recommended to guide treatment decisions.
This document summarizes a tumor board discussion of a case involving a 21-year-old patient presenting with loose stools and abdominal pain for 2 months. Key details include KRAS mutation testing of the patient's tumor sample, which showed no mutation. The discussion covers epidemiology of early-onset colorectal cancer in India, treatment options including chemotherapy and targeted therapies, and factors influencing first-line treatment decisions for metastatic colorectal cancer such as biomarker status and primary tumor location.
This document discusses the case of a 48-year-old female diagnosed with grade III invasive ductal carcinoma of the right breast in 2014. She received breast-conserving surgery along with sentinel lymph node biopsy, which showed triple positive disease. She was treated with FEC chemotherapy but received no further adjuvant treatment. In 2018, she presented with local recurrence and underwent a right modified radical mastectomy. The document discusses treatment options and ongoing clinical trials for triple positive breast cancer. Panelists debate preferences for first-line and second-line treatment of metastatic triple positive disease.
Dasatinib is an effective first-line treatment for chronic myeloid leukemia (CML) based on results from the DASISION trial. The trial showed that dasatinib induced higher and faster rates of complete cytogenetic response and major molecular response compared to imatinib. At 5 years of follow-up, dasatinib maintained superior rates of molecular responses including deeper responses below 0.1% BCR-ABL1. Dasatinib therefore provides improved long-term outcomes for patients with newly diagnosed CML compared to standard imatinib treatment.
This document summarizes key findings from the SPARTAN clinical trial evaluating the efficacy of apalutamide for the treatment of non-metastatic castration-resistant prostate cancer. The study found that apalutamide significantly reduced the risk of distant metastasis or death by 72% compared to placebo. Apalutamide also improved progression-free survival, time to symptomatic progression, and delayed the time to initiation of cytotoxic chemotherapy. The most common adverse events with apalutamide were fatigue, hypertension, and rash.
Here are a few key points regarding carfilzomib-associated cardiac adverse events based on clinical trial data:
- CHF and hypertension are the most common cardiac AEs seen with carfilzomib. Rates are generally higher than with bortezomib or lenalidomide doublets.
- Hypertension can usually be managed medically with antihypertensives like ACE inhibitors. Close monitoring of BP is important.
- Risk factors for cardiac AEs include older age, prior cardiac history, diabetes, renal dysfunction. However, events can still occur in lower risk patients.
- No definitive biomarkers yet to reliably predict risk. Troponin elevation during treatment may indicate higher risk but
- The addition of selective internal radiation therapy (SIRT) to sorafenib (SOR) did not significantly improve overall survival compared to SOR alone in patients with advanced hepatocellular carcinoma based on two randomized controlled trials.
- Subgroup analyses found potential clinical benefits for younger patients, those with non-alcoholic disease etiology, and those without cirrhosis.
- Regorafenib, a multi-kinase inhibitor, significantly improved progression-free survival, overall survival, and disease control compared to placebo in patients with hepatocellular carcinoma progressing on sorafenib.
- Lenvatinib, an oral multi-kinase inhibitor, demonstrated non-inferior
This document summarizes new adjuvant treatment strategies for early-stage HER2-positive breast cancer. It discusses trials showing improved disease-free survival when adding trastuzumab to chemotherapy as adjuvant therapy. More recent trials show additional benefits from combining trastuzumab with pertuzumab or using neratinib after initial trastuzumab therapy. The APHINITY trial found that adding pertuzumab to trastuzumab and chemotherapy significantly reduced the risk of invasive disease recurrence compared to placebo, trastuzumab and chemotherapy in the interim analysis. Benefits were greater in patients with node-positive disease or hormone receptor-negative breast cancer.
Optimal treatment sequence left side ras wt - case based (1)madurai
1. The document discusses optimal treatment sequence for left side RAS wild-type and BRAF wild-type metastatic colorectal cancer (mCRC).
2. It describes four groups of patients with metastatic disease based on resectability and provides treatment goals for each. Most patients initially present with unresectable disease.
3. Factors that influence first-line treatment choices for mCRC include biomarker status, tumor location, treatment sequence, and patient characteristics. Molecular testing for RAS and BRAF is recommended to guide treatment decisions.
This document summarizes a tumor board discussion of a case involving a 21-year-old patient presenting with loose stools and abdominal pain for 2 months. Key details include KRAS mutation testing of the patient's tumor sample, which showed no mutation. The discussion covers epidemiology of early-onset colorectal cancer in India, treatment options including chemotherapy and targeted therapies, and factors influencing first-line treatment decisions for metastatic colorectal cancer such as biomarker status and primary tumor location.
This document discusses the case of a 48-year-old female diagnosed with grade III invasive ductal carcinoma of the right breast in 2014. She received breast-conserving surgery along with sentinel lymph node biopsy, which showed triple positive disease. She was treated with FEC chemotherapy but received no further adjuvant treatment. In 2018, she presented with local recurrence and underwent a right modified radical mastectomy. The document discusses treatment options and ongoing clinical trials for triple positive breast cancer. Panelists debate preferences for first-line and second-line treatment of metastatic triple positive disease.
Dasatinib is an effective first-line treatment for chronic myeloid leukemia (CML) based on results from the DASISION trial. The trial showed that dasatinib induced higher and faster rates of complete cytogenetic response and major molecular response compared to imatinib. At 5 years of follow-up, dasatinib maintained superior rates of molecular responses including deeper responses below 0.1% BCR-ABL1. Dasatinib therefore provides improved long-term outcomes for patients with newly diagnosed CML compared to standard imatinib treatment.
This document summarizes key findings from the SPARTAN clinical trial evaluating the efficacy of apalutamide for the treatment of non-metastatic castration-resistant prostate cancer. The study found that apalutamide significantly reduced the risk of distant metastasis or death by 72% compared to placebo. Apalutamide also improved progression-free survival, time to symptomatic progression, and delayed the time to initiation of cytotoxic chemotherapy. The most common adverse events with apalutamide were fatigue, hypertension, and rash.
Here are a few key points regarding carfilzomib-associated cardiac adverse events based on clinical trial data:
- CHF and hypertension are the most common cardiac AEs seen with carfilzomib. Rates are generally higher than with bortezomib or lenalidomide doublets.
- Hypertension can usually be managed medically with antihypertensives like ACE inhibitors. Close monitoring of BP is important.
- Risk factors for cardiac AEs include older age, prior cardiac history, diabetes, renal dysfunction. However, events can still occur in lower risk patients.
- No definitive biomarkers yet to reliably predict risk. Troponin elevation during treatment may indicate higher risk but
This document summarizes the treatment landscape for ovarian cancer. It discusses standard first-line treatment options including platinum-based chemotherapy with carboplatin and paclitaxel, as well as the importance of adequate surgery to remove as much of the tumor as possible. It also reviews several phase 3 clinical trials investigating the addition of angiogenesis inhibitors like bevacizumab to chemotherapy regimens. Trials like ICON7 and GOG 218 found improved progression-free survival when bevacizumab was added to first-line treatment. For recurrent disease, bevacizumab was also found to improve outcomes when added to chemotherapy in platinum-sensitive patients based on studies like OCEANS and GOG-213. Residual
This document summarizes targeted therapies for ovarian cancer, including anti-angiogenic agents and PARP inhibitors. It discusses several studies evaluating bevacizumab, an anti-VEGF monoclonal antibody, in the first-line and recurrent platinum-sensitive settings. The GOG218 and ICON7 trials showed improved progression-free survival when bevacizumab was added to first-line chemotherapy. The OCEANS trial demonstrated significantly longer progression-free and overall survival with the addition of bevacizumab to chemotherapy for platinum-sensitive recurrent ovarian cancer. Adverse events with bevacizumab were consistent with its known safety profile.
This document summarizes clinical trial data for several drugs tested in advanced hepatocellular carcinoma (HCC) after sorafenib failure. It shows that regorafenib, cabozantinib, and ramucirumab each provided a median overall survival benefit of 1-3 months compared to placebo. Regorafenib had a median OS of 10.6 months versus 7.8 months for placebo. Cabozantinib had a median OS of 10.2 months versus 8 months for placebo. Ramucirumab plus BSC had a median OS of 8.5 months versus 7.3 months for placebo plus BSC. Lenvatinib was found to be non-inferior
1) The document discusses treatment strategies for metastatic colorectal cancer (mCRC), including the importance of multidisciplinary teams, sequencing of chemotherapy and targeted therapies, and continuing treatment beyond progression.
2) Key points addressed include using oxaliplatin or irinotecan as the chemotherapy backbone, adding targeted therapies like bevacizumab or anti-EGFR antibodies based on molecular markers, and exploring more intensive strategies like FOLFOXIRI for certain patients.
3) Maintaining quality of life across all treatment lines is emphasized as the overarching goal.
The document summarizes highlights from the 11-ICML Lugano conference in 2011, including:
1) Studies showing the impact of the tumor microenvironment in lymphoma prognosis and the predictive value of increased macrophages in Hodgkin's lymphoma biopsies.
2) High response rates to antiviral treatment in patients with indolent B-cell lymphoma associated with HCV infection.
3) A PET-based approach can effectively guide treatment for limited-stage diffuse large B-cell lymphoma.
4) R-CHOP induction followed by rituximab maintenance improves survival over R-FC induction for elderly patients with mantle cell lymphoma.
Update on Systemic Therapy for Metastatic Pancreas AdenocarcinomaOSUCCC - James
The document discusses treatment options for metastatic pancreatic cancer. For first-line therapy, FOLFIRINOX is an option but is reserved for younger, healthier patients due to toxicity. Gemcitabine plus nab-paclitaxel is a preferred first-line option. For second-line therapy after progression on gemcitabine, nanoliposomal irinotecan plus 5-FU/LV has shown a survival benefit compared to 5-FU/LV alone. Molecular profiling of pancreatic tumors has identified subtypes that could help guide targeted therapies, and immune-based approaches also offer promise. The James Cancer Hospital is conducting clinical trials evaluating novel combinations for both first-line and second-line metastatic pancreatic cancer
- Extended waiting time of more than 8 weeks between neoadjuvant chemoradiation and surgery for locally advanced rectal cancer resulted in higher rates of R0 resection and pathologic complete response compared to surgery within 8 weeks in a retrospective study. However, timing of full dose adjuvant chemotherapy may be delayed with longer waiting periods.
- Local excision after neoadjuvant chemoradiation or non-operative "wait and see" approaches may enable organ preservation in some patients who achieve a clinical complete response. However, accurate assessment of response can be challenging and long-term oncologic outcomes require further study.
Ohio State's 2016 ASH Review - ASH Review 2015Acute Leukemias and MDSOSUCCC - James
This document summarizes a presentation on acute leukemias and myelodysplastic syndrome. It discusses results from the RATIFY trial showing that the addition of midostaurin to standard chemotherapy and consolidation improved overall survival in younger adults with FLT3 mutated acute myeloid leukemia compared to placebo. It also discusses results from a phase 1/2 trial showing AG-221, a mutant IDH2 inhibitor, was well-tolerated and demonstrated clinical activity in patients with IDH2 mutated hematologic malignancies.
1. The management of prostate cancer has undergone a paradigm shift with upfront intensified treatment of metastatic hormone-sensitive prostate cancer and the introduction of new treatment options for metastatic castrate-resistant prostate cancer.
2. Final analyses of trials such as LATITUDE and ARCHES showed a survival benefit of adding abiraterone or enzalutamide to androgen deprivation therapy for high-risk metastatic hormone-sensitive prostate cancer.
3. Trials such as PROSPER and SPARTAN demonstrated a delay in disease progression with the use of enzalutamide or apalutamide for non-metastatic castrate-resistant prostate cancer.
4. Questions remain about optimal treatment sequencing
FIRE 3 Trail FOLFIRI+Cetuximab Vs FOLFIRI+BevacizumabAhmed Allam
This randomized, open-label, phase 3 trial compared FOLFIRI plus cetuximab (C+F) versus FOLFIRI plus bevacizumab (B+F) as first-line treatment for KRAS wild-type metastatic colorectal cancer. The trial found that C+F resulted in improved progression-free survival and overall survival compared to B+F. C+F was associated with increased rates of acneiform rash, paronychia, and hypomagnesemia but similar rates of other adverse events compared to B+F. The trial demonstrated that for patients with KRAS wild-type mCRC, first-line treatment with C+F provided superior
Chemoradiation therapy followed by local excision may be comparable to radical surgery for selected rectal cancer patients under certain circumstances. Studies have shown chemoradiation followed by local excision results in a pathological complete response rate of around 40-50% for cT2 tumors. For patients who achieve a complete response, the risk of local recurrence after local excision alone is very low at 0-2%. For non-responders, salvage radical surgery results in good outcomes with local recurrence rates of 50-70% after salvage surgery. This organ preservation approach offers advantages of reduced treatment related toxicity compared to radical surgery. However, long term follow up data is still needed and patient selection is important for success.
Poly-ADP-ribose polymerase inhibitors (PARPis) are the most active and interesting therapies approved for the treatment of epithelial ovarian cancer. They have changed the clinical management of a disease characterized, in almost half of cases, by extreme genetic complexity and alteration of DNA damage repair pathways, particularly homologous recombination (HR) deficiency. It is causing a paradigm shift in the first-line treatment of patients with advanced ovarian cancer
This document summarizes recent developments in the treatment of immune thrombocytopenia (ITP). It discusses new evidence on treatments for refractory ITP including rituximab, thrombopoietin receptor agonists (TPO-RAs), and long-term use of eltrombopag. A randomized controlled trial found that rituximab did not significantly reduce long-term treatment failure compared to placebo in previously steroid-treated ITP patients. Long-term use of eltrombopag for up to 3 years was found to be generally safe and effective at maintaining platelet counts. The document concludes that large, randomized studies are still needed to better understand new ITP treatment options and balancing risks versus benefits requires consideration
(Ohio State's 2016 ASH Review) ASH 2015 REVIEW – LYMPHOMA ABSTRACTSOSUCCC - James
This document summarizes key abstracts presented at the American Society of Hematology (ASH) 2015 conference related to lymphoma subtypes including mantle cell lymphoma (MCL), diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), and Hodgkin's lymphoma (HL). For MCL, abstracts showed that bortezomib maintenance after immunochemotherapy and stem cell transplant improved progression-free survival compared to consolidation or historical controls. Pre-transplant treatment with R-bendamustine induced high rates of minimal residual disease negativity associated with improved outcomes. For DLBCL, adding bortezomib to R-CHOP in non-germinal center subtype showed improved response rates
Updates On Upper Gastrointestinal Malignancies 2015OSUCCC - James
Updates On Upper Gastrointestinal Malignancies 2015
Tanios Bekaii-Saab, MD
Chief , Section of Gastrointestinal Cancers
Disease Specific Research Group Leader
Professor of Medicine and Pharmacy
OSUCCC- Arthur James Cancer Hospital
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.
Antiandrogens beyond biclutamide in metastatic prostate cancer.pptxLakhanKashyap3
- First generation anti-androgens like biclutamide were less effective than newer second generation drugs due to incomplete AR inhibition and development of resistance.
- Enzalutamide and apalutamide showed improved outcomes over standard androgen suppression in metastatic castration-sensitive and non-metastatic castration-resistant prostate cancer.
- Darolutamide demonstrated improved metastasis-free survival and was well tolerated compared to placebo in non-metastatic castration-resistant prostate cancer. Resistance to anti-androgens can develop through AR mutations, splice variants, and alternative pathways of activation.
This document summarizes the treatment landscape for ovarian cancer. It discusses standard first-line treatment options including platinum-based chemotherapy with carboplatin and paclitaxel, as well as the importance of adequate surgery to remove as much of the tumor as possible. It also reviews several phase 3 clinical trials investigating the addition of angiogenesis inhibitors like bevacizumab to chemotherapy regimens. Trials like ICON7 and GOG 218 found improved progression-free survival when bevacizumab was added to first-line treatment. For recurrent disease, bevacizumab was also found to improve outcomes when added to chemotherapy in platinum-sensitive patients based on studies like OCEANS and GOG-213. Residual
This document summarizes targeted therapies for ovarian cancer, including anti-angiogenic agents and PARP inhibitors. It discusses several studies evaluating bevacizumab, an anti-VEGF monoclonal antibody, in the first-line and recurrent platinum-sensitive settings. The GOG218 and ICON7 trials showed improved progression-free survival when bevacizumab was added to first-line chemotherapy. The OCEANS trial demonstrated significantly longer progression-free and overall survival with the addition of bevacizumab to chemotherapy for platinum-sensitive recurrent ovarian cancer. Adverse events with bevacizumab were consistent with its known safety profile.
This document summarizes clinical trial data for several drugs tested in advanced hepatocellular carcinoma (HCC) after sorafenib failure. It shows that regorafenib, cabozantinib, and ramucirumab each provided a median overall survival benefit of 1-3 months compared to placebo. Regorafenib had a median OS of 10.6 months versus 7.8 months for placebo. Cabozantinib had a median OS of 10.2 months versus 8 months for placebo. Ramucirumab plus BSC had a median OS of 8.5 months versus 7.3 months for placebo plus BSC. Lenvatinib was found to be non-inferior
1) The document discusses treatment strategies for metastatic colorectal cancer (mCRC), including the importance of multidisciplinary teams, sequencing of chemotherapy and targeted therapies, and continuing treatment beyond progression.
2) Key points addressed include using oxaliplatin or irinotecan as the chemotherapy backbone, adding targeted therapies like bevacizumab or anti-EGFR antibodies based on molecular markers, and exploring more intensive strategies like FOLFOXIRI for certain patients.
3) Maintaining quality of life across all treatment lines is emphasized as the overarching goal.
The document summarizes highlights from the 11-ICML Lugano conference in 2011, including:
1) Studies showing the impact of the tumor microenvironment in lymphoma prognosis and the predictive value of increased macrophages in Hodgkin's lymphoma biopsies.
2) High response rates to antiviral treatment in patients with indolent B-cell lymphoma associated with HCV infection.
3) A PET-based approach can effectively guide treatment for limited-stage diffuse large B-cell lymphoma.
4) R-CHOP induction followed by rituximab maintenance improves survival over R-FC induction for elderly patients with mantle cell lymphoma.
Update on Systemic Therapy for Metastatic Pancreas AdenocarcinomaOSUCCC - James
The document discusses treatment options for metastatic pancreatic cancer. For first-line therapy, FOLFIRINOX is an option but is reserved for younger, healthier patients due to toxicity. Gemcitabine plus nab-paclitaxel is a preferred first-line option. For second-line therapy after progression on gemcitabine, nanoliposomal irinotecan plus 5-FU/LV has shown a survival benefit compared to 5-FU/LV alone. Molecular profiling of pancreatic tumors has identified subtypes that could help guide targeted therapies, and immune-based approaches also offer promise. The James Cancer Hospital is conducting clinical trials evaluating novel combinations for both first-line and second-line metastatic pancreatic cancer
- Extended waiting time of more than 8 weeks between neoadjuvant chemoradiation and surgery for locally advanced rectal cancer resulted in higher rates of R0 resection and pathologic complete response compared to surgery within 8 weeks in a retrospective study. However, timing of full dose adjuvant chemotherapy may be delayed with longer waiting periods.
- Local excision after neoadjuvant chemoradiation or non-operative "wait and see" approaches may enable organ preservation in some patients who achieve a clinical complete response. However, accurate assessment of response can be challenging and long-term oncologic outcomes require further study.
Ohio State's 2016 ASH Review - ASH Review 2015Acute Leukemias and MDSOSUCCC - James
This document summarizes a presentation on acute leukemias and myelodysplastic syndrome. It discusses results from the RATIFY trial showing that the addition of midostaurin to standard chemotherapy and consolidation improved overall survival in younger adults with FLT3 mutated acute myeloid leukemia compared to placebo. It also discusses results from a phase 1/2 trial showing AG-221, a mutant IDH2 inhibitor, was well-tolerated and demonstrated clinical activity in patients with IDH2 mutated hematologic malignancies.
1. The management of prostate cancer has undergone a paradigm shift with upfront intensified treatment of metastatic hormone-sensitive prostate cancer and the introduction of new treatment options for metastatic castrate-resistant prostate cancer.
2. Final analyses of trials such as LATITUDE and ARCHES showed a survival benefit of adding abiraterone or enzalutamide to androgen deprivation therapy for high-risk metastatic hormone-sensitive prostate cancer.
3. Trials such as PROSPER and SPARTAN demonstrated a delay in disease progression with the use of enzalutamide or apalutamide for non-metastatic castrate-resistant prostate cancer.
4. Questions remain about optimal treatment sequencing
FIRE 3 Trail FOLFIRI+Cetuximab Vs FOLFIRI+BevacizumabAhmed Allam
This randomized, open-label, phase 3 trial compared FOLFIRI plus cetuximab (C+F) versus FOLFIRI plus bevacizumab (B+F) as first-line treatment for KRAS wild-type metastatic colorectal cancer. The trial found that C+F resulted in improved progression-free survival and overall survival compared to B+F. C+F was associated with increased rates of acneiform rash, paronychia, and hypomagnesemia but similar rates of other adverse events compared to B+F. The trial demonstrated that for patients with KRAS wild-type mCRC, first-line treatment with C+F provided superior
Chemoradiation therapy followed by local excision may be comparable to radical surgery for selected rectal cancer patients under certain circumstances. Studies have shown chemoradiation followed by local excision results in a pathological complete response rate of around 40-50% for cT2 tumors. For patients who achieve a complete response, the risk of local recurrence after local excision alone is very low at 0-2%. For non-responders, salvage radical surgery results in good outcomes with local recurrence rates of 50-70% after salvage surgery. This organ preservation approach offers advantages of reduced treatment related toxicity compared to radical surgery. However, long term follow up data is still needed and patient selection is important for success.
Poly-ADP-ribose polymerase inhibitors (PARPis) are the most active and interesting therapies approved for the treatment of epithelial ovarian cancer. They have changed the clinical management of a disease characterized, in almost half of cases, by extreme genetic complexity and alteration of DNA damage repair pathways, particularly homologous recombination (HR) deficiency. It is causing a paradigm shift in the first-line treatment of patients with advanced ovarian cancer
This document summarizes recent developments in the treatment of immune thrombocytopenia (ITP). It discusses new evidence on treatments for refractory ITP including rituximab, thrombopoietin receptor agonists (TPO-RAs), and long-term use of eltrombopag. A randomized controlled trial found that rituximab did not significantly reduce long-term treatment failure compared to placebo in previously steroid-treated ITP patients. Long-term use of eltrombopag for up to 3 years was found to be generally safe and effective at maintaining platelet counts. The document concludes that large, randomized studies are still needed to better understand new ITP treatment options and balancing risks versus benefits requires consideration
(Ohio State's 2016 ASH Review) ASH 2015 REVIEW – LYMPHOMA ABSTRACTSOSUCCC - James
This document summarizes key abstracts presented at the American Society of Hematology (ASH) 2015 conference related to lymphoma subtypes including mantle cell lymphoma (MCL), diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), and Hodgkin's lymphoma (HL). For MCL, abstracts showed that bortezomib maintenance after immunochemotherapy and stem cell transplant improved progression-free survival compared to consolidation or historical controls. Pre-transplant treatment with R-bendamustine induced high rates of minimal residual disease negativity associated with improved outcomes. For DLBCL, adding bortezomib to R-CHOP in non-germinal center subtype showed improved response rates
Updates On Upper Gastrointestinal Malignancies 2015OSUCCC - James
Updates On Upper Gastrointestinal Malignancies 2015
Tanios Bekaii-Saab, MD
Chief , Section of Gastrointestinal Cancers
Disease Specific Research Group Leader
Professor of Medicine and Pharmacy
OSUCCC- Arthur James Cancer Hospital
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.
Antiandrogens beyond biclutamide in metastatic prostate cancer.pptxLakhanKashyap3
- First generation anti-androgens like biclutamide were less effective than newer second generation drugs due to incomplete AR inhibition and development of resistance.
- Enzalutamide and apalutamide showed improved outcomes over standard androgen suppression in metastatic castration-sensitive and non-metastatic castration-resistant prostate cancer.
- Darolutamide demonstrated improved metastasis-free survival and was well tolerated compared to placebo in non-metastatic castration-resistant prostate cancer. Resistance to anti-androgens can develop through AR mutations, splice variants, and alternative pathways of activation.
The document discusses drug development in prostate cancer, including settings for clinical trials and endpoints accepted by regulatory agencies. It provides examples of both successful and failed phase 2 and 3 clinical trials, demonstrating the challenges of developing effective drugs to treat prostate cancer. Key approvals in 2010 included sipuleucel-T, cabazitaxel, and denosumab, representing progress after many failed drug candidates in prior years.
- Small cell lung cancer (SCLC) has seen little therapeutic advancement in over 20 years. Platinum-etoposide remains the standard chemotherapy regimen.
- For limited-stage SCLC, concurrent chemoradiation is the standard of care and provides better outcomes than sequential treatment. Early twice-daily radiotherapy with prophylactic cranial irradiation improves survival.
- For extensive-stage SCLC, prophylactic cranial irradiation after chemotherapy reduces the risk of brain metastases and improves survival compared to no cranial irradiation.
The document discusses small cell lung cancer (SCLC) treatment. It covers:
1) Chemotherapy with platinum-etoposide is the standard first-line treatment, though newer agents show promise.
2) For limited-stage SCLC, concurrent chemoradiation is the standard of care and improves survival compared to sequential treatment.
3) For extensive-stage SCLC, prophylactic cranial irradiation reduces the risk of brain metastases and improves survival when given with chemotherapy.
Dr. Paul Sabbatini: Recurrent Ovarian Cancer: Now What? (SHARE Program)bkling
On May 22, 2013, SHARE presented "Recurrent Ovarian Cancer: Now What?" The program featured Dr. Ginger Gardner and Dr. Paul Sabbatini of Memorial Sloan-Kettering Cancer Center discussing treatment strategies, as well as new approaches and agents, for managing an ovarian cancer recurrence. Listen to the audio here http://www.sharecancersupport.org/sabbatini.
The information in this presentation is not intended to be a substitute for professional medical advice, diagnosis or treatment.
1. Minimal residual disease (MRD) measured during treatment for acute lymphoblastic leukemia has been shown to strongly correlate with patient outcomes and survival rates.
2. MRD can identify low-risk and high-risk patient groups more accurately than morphological assessments alone. Several studies demonstrate integrating MRD into risk-adapted clinical trial designs.
3. MRD may serve as a surrogate endpoint for assessing response to new investigational agents in relapsed ALL, to help prioritize agents for further study and potential accelerated approval.
This document summarizes recent advances in the treatment of neuroendocrine tumors. Several new agents have shown promising results in phase II trials, including pasireotide for tumors resistant to octreotide, everolimus combined with octreotide, sorafenib, sunitinib, and temsirolimus. These agents have multiple mechanisms of action and have led to partial responses and prolonged progression-free survival in early studies. While significant progress has been made, treatment of neuroendocrine tumors remains a work in progress as several phase III trials are currently evaluating mTOR and tyrosine kinase inhibitors.
Newly approved agents in multiple myeloma: 2015 and beyondflasco_org
The document summarizes a presentation on newly approved agents and emerging treatments in multiple myeloma given in 2015 and beyond. It discusses evolving diagnostic and prognostic criteria, new indications for proteasome inhibitors carfilzomib and ixazomib in relapsed myeloma, the introduction of antibody therapies elotuzumab and daratumumab, the histone deacetylase inhibitor panobinostat, and a glimpse at future anti-myeloma treatments. Clinical trial results are presented demonstrating improved progression-free survival for combinations of carfilzomib, ixazomib, elotuzumab and other agents compared to standard therapies.
Ohio State's 2016 ASH Review - BEST OF ASH 2015 MULTIPLE MYELOMA AND PLASMA C...OSUCCC - James
This randomized clinical trial compared autologous stem cell transplantation (ASCT) versus continued therapy without transplantation in newly diagnosed multiple myeloma patients. 389 patients received induction with lenalidomide-dexamethasone (Rd) or cyclophosphamide-lenalidomide-dexamethasone (CRD). Patients were then randomized to receive ASCT or continued Rd or CRD therapy. The primary endpoint was progression-free survival (PFS). Results showed ASCT improved PFS compared to continued therapy without transplantation. However, overall survival was not significantly different between the two groups, suggesting continued therapy without ASCT may be sufficient for some patients.
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.
This document discusses optimal sequencing in metastatic castration-resistant prostate cancer (mCRPC). It presents several case studies and discusses the role of radiation, surgery, nuclear medicine, and systemic therapies. It then addresses questions about standard of care options for mCRPC, including chemotherapy, chemotherapy plus androgen deprivation therapy, chemotherapy plus antiandrogen therapy, and PARP inhibitors. Clinical trials evaluating treatments like cabazitaxel, abiraterone, and enzalutamide in mCRPC are also summarized.
The document discusses head and neck cancer, focusing on individualizing treatment. It notes that head and neck cancer incidence is increasing, with some caused by HPV. EGFR is a molecular target in these cancers. Studies combining EGFR inhibitors like cetuximab with chemoradiation in locally advanced disease showed increased toxicity but uncertain efficacy benefits. Biomarker-selected treatment de-intensification may be appropriate for HPV-positive cancers.
The document discusses adjuvant treatment options for gastric cancer based on several clinical trials. It finds that adjuvant chemotherapy provides a 5.8% absolute benefit in 5-year overall survival compared to surgery alone. Adjuvant chemoradiotherapy may provide additional benefits for patients with D1 resections, lymph node ratios over 25%, or intestinal-type gastric cancers. Specifically, one trial found 5-year disease-free survival was 55% with chemoradiotherapy versus 28% with chemotherapy alone for these high-risk patients. The document concludes that adjuvant chemoradiotherapy should be considered for these poor prognosis patients when neoadjuvant treatment is not possible due to poor performance status.
RR-17%
mPFS-4.5 mon
mOS-9.2 mon
Phase III trial
Rec/met HNSCC
N=326
Mtx vs Mtx+BV
No benefit
[1] The document discusses targeted therapies for head and neck squamous cell carcinoma (HNSCC).
[2] It summarizes genetic alterations commonly seen in HNSCC and targeted agents used to treat HNSCC including EGFR inhibitors like cetuximab, IGF inhibitors, VEGF receptor inhibitors, and other non-receptor targets.
[3] The document analyzes clinical trials of cetuximab, panitumumab
ROLE OF DARATUMUMAB IN NEWLY DIAGNOSED MULTIPLE MYELOMA.pptxSeraj Aldeen
1. The document discusses three phase 3 trials (CASSIOPEIA, MAIA, and ALCYON) that evaluated the role of daratumumab in frontline treatment of multiple myeloma.
2. The MAIA trial showed that in transplant-ineligible newly diagnosed multiple myeloma patients, daratumumab with lenalidomide and dexamethasone (D-Rd) resulted in significantly longer progression-free survival compared to lenalidomide and dexamethasone (Rd) alone, with median PFS not reached for D-Rd versus 34.4 months for Rd.
3. D-Rd also resulted in higher overall response and complete response rates compared to Rd.
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.
Sequencing therapy for crcp a practical approachMohamed Abdulla
This document discusses sequencing therapy for castration-resistant prostate cancer (CRPC). It provides an overview of prostate cancer as an androgenic disease and summarizes several key clinical trials investigating the efficacy of abiraterone and enzalutamide in both pre-docetaxel and post-docetaxel CRPC patients. It concludes by presenting NCCN guidelines for sequencing CRPC therapies based on disease stage and symptoms.
This document discusses recent updates in lung cancer. It begins by noting that lung cancer is the leading cause of cancer death in the US and is often diagnosed at an advanced stage. Screening with low-dose CT scans can detect lung cancer earlier and has been shown to decrease lung cancer mortality by 20% compared to chest x-rays. The National Lung Screening Trial established low-dose CT screening as an effective screening method for those at high risk. Biomarker testing is important to identify driver mutations and guide targeted therapy options, though barriers like tissue availability and turnaround time exist. Osimertinib has demonstrated superior progression-free survival compared to earlier EGFR TKIs for patients with EGFR-mut
This document discusses biomarkers in cancer immunotherapy. It begins by defining an immuno-biomarker as a measurable indicator of the immune system's response to cancer or its treatment. Biomarkers can be used to predict response, resistance, toxicity, and hyperprogression to immunotherapy. Popular biomarkers discussed include PD-L1 expression, tumor mutational burden (TMB), and T-cell receptor (TCR) repertoire. The predictive value of these biomarkers is explored for various cancer types. Limitations and heterogeneity of PD-L1 expression are also noted. The document examines ongoing efforts to standardize the measurement and clinical application of biomarkers to optimize immunotherapy.
This document provides a pathology report for a 34-year-old female patient. It summarizes the findings from biopsies of the right and left breast. For the right breast, it finds an invasive ductal carcinoma measuring 1.5 x 1.3 x 1 cm. Three of 39 lymph nodes from the right axilla showed metastatic carcinoma. The left breast tissue showed benign findings with no evidence of malignancy. The conclusion is infiltrating ductal carcinoma of the right breast with metastasis to 3 lymph nodes, classified as T1c/N1a.
The document discusses several antibody-drug conjugates (ADCs) that are being studied or developed for the treatment of non-small cell lung cancer (NSCLC). It summarizes clinical trial results of trastuzumab emtansine and trastuzumab deruxtecan for HER2-positive NSCLC, and sacituzumab govitecan and datopotamab deruxtecan for Trop-2 positive NSCLC. It also briefly mentions ADCs in development that target HER3, c-MET, CEACAM5, Axl, PTK7, NaPi2b, and Nectin-4 for lung cancer. The document concludes by reviewing a phase 1 clinical trial of
Indian women are more likely to have certain types of cancer according to Dr. R. Rajkumar. Over the last 25 years, large cancer trials have led to better outcomes for patients. Current research focuses on understanding cancer genes and cell growth to develop more targeted individualized treatments.
This document discusses treatment options for triple negative breast cancer (TNBC). It begins with a case study of a 56-year-old female patient diagnosed with TNBC. It then provides details on the characteristics and subtypes of TNBC, noting that it is an aggressive disease with poor prognosis. Current treatment approaches for metastatic TNBC are discussed, including sequential single-agent chemotherapy with taxanes, anthracyclines, antimetabolites, and platinum agents. Several key clinical trials comparing different chemotherapy regimens for TNBC are summarized, such as the TNT trial comparing carboplatin and docetaxel, and the TNACITY trial evaluating nab-paclitaxel plus carboplatin
This document provides guidelines for the management of gestational trophoblastic neoplasia (GTN). It outlines recommendations for initial treatment, monitoring, diagnosis of persistent postmolar GTN, and treatment approaches depending on the risk level and response. For low-risk GTN, single-agent chemotherapy such as methotrexate or dactinomycin is recommended. For high-risk or relapsed GTN, more intensive regimens including EMA/CO are used. Treatment is monitored closely with hCG assays and adjusted based on the tumor response.
The OUTBACK trial compared standard chemoradiation (CRT) to CRT plus adjuvant carboplatin and paclitaxel (ACT) in patients with locally advanced cervical cancer. Over 900 patients were randomized 1:1 to receive either CRT alone or CRT followed by ACT. Baseline characteristics were well balanced between the two arms. The primary endpoint was overall survival and secondary endpoints included progression-free survival, adverse events, sites of recurrence, and patient-reported outcomes.
This document discusses a clinical case presentation of a patient with metastatic renal cell carcinoma (mRCC). Key details include that the patient previously underwent nephrectomy and radiation therapy and is now being discussed for systemic therapy options. The document reviews several clinical trials evaluating different combination regimens for first-line and subsequent lines of treatment in mRCC. Factors like prognostic risk categories and biomarkers are discussed for guiding treatment selection. The merits and limitations of different studies are evaluated.
Metronomic chemotherapy involves administering lower doses of chemotherapy drugs more frequently to target tumor growth. This summary approach has three potential mechanisms of action - inhibiting angiogenesis, stimulating the immune system, and directly targeting tumor cells. It yields long-term improved outcomes despite slower initial decreases in tumor size compared to maximum tolerated dose regimens. Clinical trials have shown metronomic chemotherapy to be an effective treatment approach in several cancer types including breast, colon, ovarian and prostate cancer when used as a single agent or in combinations.
- The patient is a 36-year-old man who underwent neoadjuvant chemoradiotherapy in 2015 for rectal cancer.
- In 2021, he presented with frequent urination. Imaging showed a large recurrent mass involving abdominal structures.
- Biopsy of the skin deposit was suspicious for metastatic mucinous carcinoma.
- The case discusses the current treatment approaches for locally advanced rectal cancer, including neoadjuvant and total neoadjuvant therapy options, and choices for chemotherapy and radiotherapy.
This presentation discusses breast cancer, specifically hormone receptor positive/HER2 negative breast cancer. It provides statistics on the distribution of breast cancer molecular subtypes in the United States. It also discusses the evolving treatment landscape for hormone receptor positive metastatic breast cancer, including the approvals and use of targeted therapies in combination with endocrine therapy, such as CDK4/6 inhibitors. Clinical trial results are summarized that demonstrate improved progression-free survival when a CDK4/6 inhibitor is added to first-line endocrine therapy for advanced hormone receptor positive breast cancer. An approach to personalized therapy is proposed based on factors such as endocrine sensitivity and molecular alterations.
This document discusses a case of a 64-year-old man presenting with right flank pain and a history of smoking who is found to have clear-cell renal cell carcinoma (RCC). He undergoes a right radical nephrectomy and pathology confirms grade 3 clear-cell RCC without margins or lymph node involvement. Small lung nodules are detected 18 months later and biopsy confirms metastatic clear cell RCC. Systemic therapy options for the metastatic disease are discussed, including tyrosine kinase inhibitors, immunotherapy, and their combinations. Ongoing trials of immunotherapy in the adjuvant and metastatic settings are also summarized. Risk stratification models and their impact on treatment selection are reviewed.
Cervical cancer is the second most common cancer in women worldwide. Over 500,000 women die from cervical cancer each year, most in low- and middle-income countries. The document discusses the epidemiology, risk factors, symptoms, diagnosis, staging, treatment, and prevention of cervical cancer. Screening and HPV vaccination can prevent cervical cancer but coverage is still low in India.
Case discussion ovarian cancer (nx power lite copy)madurai
This document discusses a case report from Dr. R. Rajkumar regarding genetic testing results for a 55-year-old female patient. Genetic testing of the patient's sample using next generation sequencing did not detect any deleterious mutations in the BRCA1 or BRCA2 genes. The report provides background information on BRCA gene mutations and their association with breast and ovarian cancer risk. It also discusses the role of homologous recombination repair and how mutations in genes involved in this pathway can lead to homologous recombination deficiency.
This document discusses recent updates in treating metastatic colorectal cancers. It presents several case studies of patients diagnosed with colorectal cancer and large metastatic tumors. It then reviews the epidemiology of colorectal cancer in India, including rising incidence rates. The document outlines different classifications and treatment approaches for patients with metastatic disease, including the goal of increasing overall survival. It also discusses the increasing number of treatment options and challenges of personalizing therapy based on a patient's molecular profile.
This document discusses genetic testing for breast and ovarian cancer risk. It notes that not everyone with breast cancer needs genetic testing, but certain high-risk groups should be referred for further evaluation, such as those diagnosed at a young age or with a family history. Genetic testing can find pathogenic mutations that increase cancer risk or identify variants of uncertain significance. A positive test result indicates increased cancer risks and screening/prevention options, while a negative result does not rule out hereditary risk based on personal/family history factors. Over time, the rate of uncertain variants from BRCA1/2 testing has declined as knowledge improves. Most breast cancers still do not have an identifiable inherited genetic mutation.
Slide deck cancer care during covid 19 pandemicmadurai
This document provides guidance for cancer care during the COVID-19 pandemic from several medical organizations. It discusses that cancer patients may be more susceptible to COVID-19 and have poorer outcomes. It recommends postponing non-urgent visits and elective surgeries, continuing critical cancer treatments when possible, and increasing telehealth to reduce infections. Safety measures like PPE and social distancing are crucial to protect staff and patients. Treatment should be individualized based on risk factors.
A 25-year-old male presented to the emergency department with ischemic low flow priapism. His priapism was caused by a newly diagnosed chronic myeloid leukemia (CML). The doctor is considering various treatment options for managing the priapism caused by CML, including shunts, leukopheresis, chemotherapy, and tyrosine kinase inhibitors like imatinib. The doctor is also considering standard first-line treatment options for newly diagnosed CML in the chronic phase, such as imatinib 400mg or 600mg daily, dasatinib 100mg daily, nilotinib 300mg daily, or hematopoietic stem cell transplantation.
- HER2-positive early-stage breast cancer can be treated with neoadjuvant chemotherapy to shrink tumors and increase the rate of breast conservation.
- The addition of trastuzumab to neoadjuvant chemotherapy significantly increases pathological complete response (pCR) rates. Achieving pCR correlates with improved long-term outcomes.
- Adding pertuzumab to trastuzumab and chemotherapy further increases pCR rates compared to chemotherapy and trastuzumab alone. Trials also suggest improved long-term outcomes with dual anti-HER2 blockade.
Histololgy of Female Reproductive System.pptxAyeshaZaid1
Dive into an in-depth exploration of the histological structure of female reproductive system with this comprehensive lecture. Presented by Dr. Ayesha Irfan, Assistant Professor of Anatomy, this presentation covers the Gross anatomy and functional histology of the female reproductive organs. Ideal for students, educators, and anyone interested in medical science, this lecture provides clear explanations, detailed diagrams, and valuable insights into female reproductive system. Enhance your knowledge and understanding of this essential aspect of human biology.
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
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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).
Basavarajeeyam is a Sreshta Sangraha grantha (Compiled book ), written by Neelkanta kotturu Basavaraja Virachita. It contains 25 Prakaranas, First 24 Chapters related to Rogas& 25th to Rasadravyas.
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6. Clinical Trials are of Two Broad Groups
Chemo-Hormonal Therapy
‒ CHAATERED
‒ STAMPEDE
Trials of Androgen Signaling Inhibitors
LATITUDE ARCHES
STAMPEDE ENZAMET
TITAN
7. ASCO GU 2020: Time to Second Progression in Patients
with Metastatic Castration-Sensitive Prostate Cancer from
TITAN by First Subsequent Therapy (Hormonal vs. Taxane)
8.
9.
10.
11.
12. ASCO GU 2020: Luminal B Subtype as a Predictive
Biomarker of Docetaxel Benefit for Newly Diagnosed
Metastatic Hormone-Sensitive Prostate Cancer
(mHSPC): A Correlative Study of E3805 CHAARTED
13. E3805 CHAARTED
This trial has been previously published and sought to evaluate the effect of
androgen deprivation therapy alone versus in conjunction with docetaxel.
Based on normalized gene expression, subjects were classified as luminal A, luminal
B or basal subtype.
Multivariable analyses adjusted for ECOG status, de novo metastasis vs prior local
therapy and volume of disease.
The study was designed to evaluate both overall survival and time to castration
resistance.
Successful profiling was completed in 80 percent of specimens (160 out of 198).
Half of the patients were classified as luminal B (80), 48% as basal (77) and 2%
luminal A.
High volume disease was equally present in the luminal B and basal subtypes, 79%
versus 78% respectively.
14.
15.
16. ASCO GU 2020: Treatment Selection in CSPC: Considerations
Now and Downstream in an Evolving Therapeutic Landscape
17.
18. ASCO 2020: Phase III Study of Pembrolizumab plus
Enzalutamide and ADT for Patients with Metastatic
Hormone-Sensitive Prostate Cancer: KEYNOTE-991
20. ASCO 2020 GU: Efficacy of Enzalutamide + ADT in
Metastatic Hormone-sensitive Prostate Cancer by
Pattern of Metastatic Spread: ARCHES Post Hoc
Analyses
26. Pembrolizumab + Enzalutamide for Enzalutamide-Resistant
mCRPC (KEYNOTE-199): Background
Pembrolizumab monotherapy active with durable response in PD-L1+ mCRPC[1,2]
Phase II study (N = 28): pembrolizumab + enzalutamide active in patients with PD on
enzalutamide[3]
Phase II KEYNOTE-199 study designed to evaluate pembrolizumab in multiple cohorts
of patients with mCRPC after disease progression on chemotherapy and/or targeted
endocrine therapy
‒ Cohorts 1-3: data previously reported for patients with RECIST-measurable PD-L1+,
PD-L1–negative, or bone-predominant disease previously treated with docetaxel and
≥ 1 targeted endocrine therapy[1]
‒ Cohorts 4 and 5 included in this report: RECIST-measurable disease and bone-
predominant metastatic, RECIST-nonmeasurable disease with progression on
enzalutamide after initial response[4]
1. Antonarakis. JCO. 2020;38:395. 2. Hansen. Ann Oncol. 2018;29:1807. 3. Graff. JCO. ASCO 2018. Abstr 5047. 4. Graff. ASCO GU 2020. Abstr 15.
27. KEYNOTE-199 Cohorts 4 and 5: Phase II Study Design
Primary endpoint: ORR in cohort 4 by RECIST v1.1 (BICR)
Secondary endpoints: DCR (RECIST v1.1), PFS (radiographic; RECIST v1.1), PSA response
rate, OS, safety (cohorts 4 and 5), DOR (RECIST v1.1, cohort 4)
Patients with metastatic
CRPC with progression on
enzalutamide after initial
response; chemo naive but
previous abiraterone
allowed; ECOG PS 0/1;
(N = 126)
Cohort 1: PD-L1 positive
Cohort 3: Bone mets
Cohort 2: PD-L1 negative
Cohort 4:
RECIST-measurable disease
(n = 81)
Cohort 5: Bone-only or bone-
predominant, metastatic, RECIST-
nonmeasurable disease
(n = 45)
Graff. ASCO GU 2020. Abstr 15.
Tumor imaging and PSA assessment
Q9W in Yr 1, then Q12W
Survival: assessed Q12W during follow-up
Pembrolizumab 200 mg Q3W +
Enzalutamide (up to 35 cycles)
Patients with metastatic CRPC
previously treated with
docetaxel and ≥ 1 targeted
endocrine therapy
Pembrolizumab 200 mg Q3W
28. KEYNOTE-199 Cohorts 4 and 5: Patient Disposition
Graff. ASCO GU 2020. Abstr 15.
Characteristic, n Cohort 4: RECIST Measurable
Cohort 5: Bone Predominant,
RECIST Nonmeasurable
Enrolled 81 47
Discontinued --
Screening failure: 1
Withdrawal of consent: 1
Treated 81 45
Discontinued
Radiographic progression: 44
AE: 14
Clinical progression: 6
Withdrawal of consent: 3
Physician decision: 1
Radiographic progression: 23
AE: 7
Clinical progression: 5
Withdrawal of consent: 4
Physician decision: 0
Treatment ongoing at data cutoff
(June 24, 2019)
13 6
Median time to data cutoff, mos 15.3 (range: 6.7-20.7) 19.1 (range: 6.5-20.9)
34. KEYNOTE-199 Cohorts 4 and 5: Summary
• In patients with RECIST-measurable and bone-predominant mCRPC and
progression on enzalutamide, the addition of pembrolizumab to
enzalutamide was active with durable responses.
• In cohort 4, 12% achieved ORR, with a 51% DCR and DoR of 6.3 mos
• In cohort 5, DCR was 51%
• Radiographic PFS was 4.2 mos in cohort 4 and 4.4 mos in cohort 5
• Median OS was not reached in cohort 4 and 18.8 mos in cohort 5
• Safety: manageable; rash resolves with standard-of-care treatment.
• Pembrolizumab/enzalutamide vs placebo/enzalutamide for mCRPC being
evaluated in randomized phase III KEYNOTE-641 trial (NCT03834493).
Graff. ASCO GU 2020. Abstr 15.
39. ASCO GU 2020: Efficacy of Olaparib by Prior Taxane Use in
Patients with Metastatic Castration-Resistant Prostate Cancer
and Homologous Recombination Repair Gene Alterations
44. ASCO GU 2020: Final overall survival (OS) from
PROSPER: A phase III, randomized, double-blind,
placebo (PBO)-controlled study of enzalutamide (ENZA)
in men with non-metastatic castration resistant
prostate cancer (nmCRPC).
45. M0 CRPC - PROSPER Trial OS data
27% lower risk of death in
Enzalutamide arm
May 2020
NCCN 2020
Only Enzalutamide
is Category 1
(Apa, Daro not available in India)
46. ASCO GU 2020: Real world analysis of Prostate Specific
Antigen outcomes among patients with Metastatic
Castrate Resistant patients treated with Enzalutamatide
47. Introduction
• Advanced prostate cancer patients will eventually progress to metastatic and non-metastatic castration
resistant prostate cancer.
• Enzalutamide is approved for the treatment of mCRPC and nmCRPC, and more recently, mHSPC as well.
• There have been only a few real-world studies analyzing PSA outcomes in chemotherapy-naïve men with
mCRPC treated with Enzalutamide.
Objective
Retrospective cohort study to describe PSA response in chemotherapy-naïve
men with mCRPC treated with Enzalutamide
1. 2020 Genitourinary Cancers Symposium, ASCO GU #GU20, February 13-15, 2020, San Francisco, California
2. Beer TM, Armstrong AJ, Rathkopf DE, et al. Enzalutamide in Metastatic Prostate Cancer before Chemotherapy. New England Journal of Medicine 2014; 371(5): 424-33.
48. Study Design
The primary endpoint was PSA progression, defined as the time from
baseline to the first >25% increase and an absolute increase > 2 ng/dl
above baseline or nadir.
1. 2020 Genitourinary Cancers Symposium, ASCO GU #GU20, February 13-15, 2020, San Francisco, California
2. Beer TM, Armstrong AJ, Rathkopf DE, et al. Enzalutamide in Metastatic Prostate Cancer before Chemotherapy. New England Journal of
Medicine 2014; 371(5): 424-33.
49. Patients Characteristics
1. 2020 Genitourinary Cancers Symposium, ASCO GU #GU20, February 13-15, 2020, San Francisco, California
2. Beer TM, Armstrong AJ, Rathkopf DE, et al. Enzalutamide in Metastatic Prostate Cancer before Chemotherapy. New England Journal of
Medicine 2014; 371(5): 424-33.
50. Result
•The median follow-up time was 12.5 (7.6-19.4) months with a median of four PSA
tests was observed.
• Median reduction in PSA from baseline of 58% (-89% to 1%), with 14.2% of men
reaching an undetectable PSA.
• Longer time to PSA progression reported compared toPREVAIL (11.2 months).
1. 2020 Genitourinary Cancers Symposium, ASCO GU #GU20, February 13-15, 2020, San Francisco, California
2. Beer TM, Armstrong AJ, Rathkopf DE, et al. Enzalutamide in Metastatic Prostate Cancer before Chemotherapy. New England Journal of
Medicine 2014; 371(5): 424-33.
Typical patient presentation as they move through different stages. We can see that patient moves from urologist care to oncologist care as the disease worsens.
Androgen deprivation (ie, serum testosterone less than or equal to 50 ng/dL).
The promising results seen with radium-223, enzalutamide, and abiraterone have triggered interest in using these drugs earlier in castration-resistant disease, and they are now approved in both the pre- and postchemotherapy state. The role of chemotherapy— still a good option, especially after progression on androgen pathway drugs—may be shifted far down the road.