Ep 67: SITC white paper on ICI resistance

SummaryIn this conversation, James Larkin and Sapna Patel discuss the consensus definitions for resistance to immune checkpoint inhibitors, focusing on a recent paper from the Journal of Immunotherapy of Cancer. They explore the complexities of primary and secondary resistance, the importance of defining these terms for clinical trials, and the challenges in trial design and control arms. The discussion emphasizes the need for clear definitions to improve patient outcomes and guide future research in oncology.Keywordsimmune checkpoint inhibitors, cancer treatment, resistance, clinical trials, melanoma, PD-1, adjuvant therapy, response rate, tumor sensitivity, oncologyTakeawaysResistance to immune checkpoint inhibitors is a major challenge in melanoma treatment.Primary resistance occurs when there is no benefit from treatment, while secondary resistance follows initial benefit.Defining resistance is crucial for clinical trials and understanding patient populations.The duration of drug exposure is key in determining resistance types.Clinical trial design must consider the expectations of efficacy in control arms.Investigators should be cautious about the definitions of patient populations in trials.Response rates of 15-20% are considered significant for primary resistance.Secondary resistance may show higher response rates due to residual sensitivity.Clear definitions help in layering data for future research.Collaboration among clinicians, industry, and regulatory bodies is essential for advancing cancer treatment.Sound Bites"It's probably the biggest challenge we now have in clinic.""There's something in the middle.""I think that's where we might need to be there."Chapters00:00 Introduction to Immune Checkpoint Inhibitors and Resistance08:08 Understanding Resistance: Definitions and Scenarios14:47 Primary vs. Secondary Resistance in Clinical Trials22:00 Trial Design and Control Arms in Immunotherapy30:36 Conclusions and Future Directions33:28 outro fade long expo.mp4