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MedicalResearch.com Interview with: Robert L. Coleman, MD, FACOG, FACS Chief Scientific Officer US Oncology Research MedicalResearch.com: What is the background for this study? Response: For years, there has been general support for surgery in patients with recurrent ovarian cancer supported by reams of retrospective studies that suggest patients live longer if they have surgery preceding chemotherapy. Suggested hypotheses from these trials were that patients most likely to benefit from the procedure were those with good performance status (could tolerate the procedure), had long platinum-free interval (surrogate for potential for chemotherapy response) and those in whom all disease could be resected. Each of these are also characteristics that would portend a good prognostic cohort in general and would likely do better than other patients without these characteristics. So there was a strong selection bias in these retrospective surveys. Thus, the call for randomized trials. GOG-213 was launched in 2007 with 2 primary endpoints: 1. Determine the impact of adding bevacizumab to paclitaxel/carboplatin in patients with platinum-sensitive recurrent ovarian cancer, and 2. Determine if surgery increases overall survival.  MedicalResearch.com: What are the main findings? Response: We found first that bevacizumab added to chemotherapy in these patients increased both PFS and OS. We published those data in 2017. Read the full article

MedicalResearch.com Interview with: Dr. Clement Bidard Francois-Clement Bidard, MD PhD Head of Breast Cancer Group, Institut Curie Professor of Med. Oncology, UVSQ/Paris MedicalResearch.com: What is the background for this study? Response: A timely question is how to optimize the endocrine therapy of ER+ HER2- metastatic breast cancers? Aromatase inhibitors (AI) are currently the standard of care in first line, in combination with CDK4/6 inhibitors. Mutations in the estrogen receptor gene (ESR1) can be detected in up to 40% of AI-resistant metastatic breast cancers, but no data was available in the current first line setting (AI combined to CDK4/6 inhibitor). This exploratory study of the first line PADA-1 study reports on the detection rate of ESR1 mutations in cell-free DNA from an “AI-sensitive” population (with no metastatic relapse during adjuvant AI therapy), before the start of therapy (at inclusion). As expected, we found a low prevalence of 3.2% in the general population (N=1,017 patients included). The prevalence of ESR1 mutations among subgroups appeared primarily driven by the type of adjuvant endocrine therapy: patients with prior exposure to adjuvant therapy with AI displayed the highest prevalence of ESR1 mutations (7.1%), followed by patients with no prior adjuvant endocrine therapy (mostly de novo stage IV; ESR1 mutation prevalence: 2.4%). Patients who received adjuvant endocrine therapy with no AI (e.g. tamoxifen only) had the lowest ESR1 mutation prevalence (1.2%). MedicalResearch.com: What are the main findings? Response: We found that patients with ESR1 mutations at baseline had a significantly shorter median PFS under AI and palbociclib (11 vs 26.7 mo; HR=2.3). Among the ESR1-positive patients at baseline, we showed that two-thirds had an early clearance of ctDNA (no ESR1 mutation detected after 1 month on AI and palbociclib). These patients had a much longer PFS than those who still displayed detectable ESR1 mutations at 1 month.  MedicalResearch.com: What should readers take away from your report? Response: ESR1 mutations were known to be positively selected during AI therapy at metastatic stage; the PADA-1 data show that they are also selected during adjuvant AI therapy and can be detected prior at metastatic relapse, prior to any treatment. Our data confirm that ESR1 mutations are associated with a worse prognosis under AI-based therapy, yet both the median PFS achieved in the ESR1-mutant subgroup (11 months) and ctDNA clearance observed in many patients suggest that the combination of AI and palbociclib retain some activity in that population. These findings may partly explain the results of the PARSIFAL trial (also disclosed at ASCO 20), which had very similar inclusion criteria and showed no superiority of fulvestrant over AI when combined with Palbociclib in an AI-sensitive population. MedicalResearch.com: What recommendations do you have for future research as a result of this work? Response: The key question is how and when to use fulvestrant or the many Selective Estrogen Receptor Degraders (SERDs) currently in development. We know that, when patients treated with fulvestrant as single agent in the late lines have very short PFS – even in presence of ESR1 mutations (EFECT trial, PlasmaMATCH study). In the first line setting, in combination with CDK4/6 inhibitors, the PARSIFAL study just taught us that fulvestrant is no better than AI in an all-comers AI-sensitive population. Our hypothesis in the PADA-1 trial (which results will be known in 2021) is that the use of fulvestrant should be triggered by the emergence of an ESR1-mutated subclone during the first line AI-based therapy. This will likely pave the way for the future development of new oral SERDs. MedicalResearch.com: Is there anything else you would like to add?  Response: PADA-1 is funded by a research grant to UCBG. Personal disclosures of Prof Bidard include travel support, advisory and speaker fees from Pfizer; advisory fees from Radius Pharma; travel support, advisory and speaker fees from Novartis; advisory fees from Lilly.Citation:  DOI: 10.1200/JCO.2020.38.15_suppl.1010 Journal of Clinical Oncology 38, no. 15_suppl (May 20, 2020) 1010-1010. Published online May 25, 2020. The information on MedicalResearch.com is provided for educational purposes only, and is in no way intended to diagnose, cure, or treat any medical or other condition. Always seek the advice of your physician or other qualified health and ask your doctor any questions you may have regarding a medical condition. In addition to all other limitations and disclaimers in this agreement, service provider and its third party providers disclaim any liability or loss in connection with the content provided on this website.   Read the full article

MedicalResearch.com Interview with: Debra A. Patt, MD, PhD, MBA, FASCO Editor-in-chief of the Journal of Clinical Oncology - Clinical Cancer Informatics Medical oncologist at Texas Oncology, and US Oncology Research Breast Cancer Committee member MedicalResearch.com: What is the background for this study? Response: Cancer care is increasing in complexity with differentiation of cancer subtypes, new treatments, and treatment sequences and combinations.  Complying with evidence based therapy has become an increasing challenge.  We see that compliance with guideline based care across the country is highly variable. Our study evaluated an electronic health record based Clinical Decision Support System to facilitate compliance with evidence based guidelines--or pathways--to deliver care to adult patients with cancer. MedicalResearch.com: What are the main findings?  Response: In evaluating almost 30,000 patients across 9 statewide practices we found that The Clinical decision support system DOES significantly improve compliance with evidence based treatment Assessable data and understanding of variance reporting also improved substantially Clinical Decision Support Systems are a way to influence clinician behavior at the point of care and drive high quality cancer care  MedicalResearch.com: What should readers take away from your report? In complex systems like cancer care, clinical decision support is a clinical informatics tool that can improve the quality of care.  Given the tremendous variability across the country in compliance with evidence based guidelines, it is a tremendous enhancement in cancer care quality. The system we use, clear value plus, is actually a value based guideline pathway that incorporates the best, least toxic, highest value treatment choices so it is also a way to steward healthcare spending. MedicalResearch.com: What recommendations do you have for future research as a result of this work?  Clinical decision support systems can grow and become more useful and patients and providers will benefit. Clinical decision support and other clinical informatics solutions introduce efficiency and can enhance the quality of patient care and the patient experience. We now link our clinical decision support system to educational information to patients so when their doctor discusses new treatments they have a tailored document that summarizes the discussion. Growing these systems to enhance healthcare quality and enhance the patient experience improves patient care.  Any disclosures? This research was conducted within The US Oncology Network, and I am a Vice President of Texas Oncology and a Medical Director of Analytics for McKesson.  Citation: DOI: 10.1200/JCO.2020.38.15_suppl.2045 Journal of Clinical Oncology 38, no. 15_suppl (May 20, 2020) 2045-2045. Published online May 25, 2020. The information on MedicalResearch.com is provided for educational purposes only, and is in no way intended to diagnose, cure, or treat any medical or other condition. Always seek the advice of your physician or other qualified health and ask your doctor any questions you may have regarding a medical condition. In addition to all other limitations and disclaimers in this agreement, service provider and its third party providers disclaim any liability or loss in connection with the content provided on this website.   Read the full article

Dr. Berdeja Dr. Jesus G. Berdeja, MD Director of Myeloma Research Sarah Cannon Nashville, TN MedicalResearch.com: What is the background for this study? Response: Despite many advances in the treatment of multiple myeloma in recent years, the majority of patients will progress through all available therapies and ultimately succumb to their disease.  Thus there is still a high unmet medical need. The Phase 1b/2 CARTITUDE-1 study evaluates the safety and efficacy of JNJ-4528, an investigational BCMA-directed CAR-T therapy, in the treatment of patients with relapsed or refractory multiple myeloma. Participants in this study have already tried approved therapies, and had received a median of five prior treatment regimens and their median overall survival is less than 12 months.  MedicalResearch.com: What are the main findings? Response: Initial findings from the Phase 1b portion of the CARTITUDE-1 study -- reported in December at the American Society of Hematology Annual Meeting -- showed that JNJ-4528 led to early and deep responses, with 100 percent of patients (n=29) achieving a response at a median six-month follow-up. The longer-term follow-up results I’ll be presenting at ASCO show that all patients responded to treatment and that the responses were deep and durable, with 86 percent of patients achieving stringent complete response at a median follow-up of 11.5 months, and 86 percent of patients alive and progression free at 9 months. In addition, 97 percent of patients achieved a very good partial response or better, and three percent of patients achieved a partial response.  Aside from the well described toxicities associated with CART therapy such as cytokine release syndrome and low blood counts, JNJ4528 was generally well tolerated with no unexpected toxicity. MedicalResearch.com: What should readers take away from your report? Response: In short, these longer-term results from the CARTITTUDE-1 study show the continued treatment benefit of JNJ-4528 in heavily pretreated patients who have few or no remaining treatment options. Furthermore, this is accomplished with a one-time treatment without continued dosing or use of maintenance.  Patients with multiple myeloma are in need of new options that may provide a durable response and a tolerable safety profile, and that’s what we found in these most recent findings. Encouraging are both the relatively high rate of stringent complete responses, as well as the progression-free survival.  MedicalResearch.com: What recommendations do you have for future research as a result of this work?  Response: Ultimately, studies will evaluate the initiation of CAR-T in earlier lines of therapy. Most immediately, CARTITUDE-2, a global, multi-cohort Phase 2 study, will investigate JNJ-4528 in patients with multiple myeloma in various clinical settings. That study will evaluate minimal residual disease of participants who receive JNJ-4528. CARTITUDE-4, a global Phase 3 study, will investigate JNJ-4528 in patients who have received only 1-3 prior lines of therapy, including a proteasome inhibitor and an immunomodulatory drug and who are refractory to lenalidomide. That study will evaluate the efficacy of JNJ-4528 compared to standard therapies including daratumumab, pomalidomide and low-dose dexamethasone or pomalidomide, bortezomib and low-dose dexamethasone.  MedicalResearch.com: Is there anything else you would like to add? Response:  In 2020, an estimated 32,270 people will be diagnosed and an estimated 12,830 will die from multiple myeloma in the United States, according to the American Cancer Society. Based on the initial experiences that we’re seeing in relapsed/refractory multiple myeloma, BCMA CAR-T therapies like JNJ-4528 have the potential to transform the treatment of what is today and incurable blood cancer. Any Disclosures? Consulting or Advisory Role - Amgen (Inst); BioClinica (Inst); Bristol-Myers Squibb (Inst); Celgene (Inst); crispr therapeutics (Inst); Janssen (Inst); Janssen (Inst); Karyopharm Therapeutics (Inst); Kite Pharma (Inst); Legend Biotech (Inst); prothena (Inst); SERVIER (Inst); Takeda (Inst) Research Funding - Abbvie (Inst); Acetylon (Inst); Amgen (Inst); Bluebird Bio (Inst); Bristol-Myers Squibb (Inst); Celgene (Inst); Constellation (Inst); CURIS (Inst); Genentech/Roche (Inst); Glenmark (Inst); Janssen (Inst); Kesios (Inst); Lilly (Inst); Novartis (Inst); poseida therapeutics (Inst); Sanofi (Inst); Takeda (Inst); Teva (Inst); Vivolux (Inst)   Citation: ASCO 2020 abstract: Update of CARTITUDE-1: A phase Ib/II study of JNJ-4528, a B-cell maturation antigen (BCMA)-directed CAR-T-cell therapy, in relapsed/refractory multiple myeloma.        The information on MedicalResearch.com is provided for educational purposes only, and is in no way intended to diagnose, cure, or treat any medical or other condition. Always seek the advice of your physician or other qualified health and ask your doctor any questions you may have regarding a medical condition. In addition to all other limitations and disclaimers in this agreement, service provider and its third party providers disclaim any liability or loss in connection with the content provided on this website.   Read the full article