Ep 39: LEAP 004 & 003

Summary (Coach) Owen is in a seriously bad mood with James at the moment! But James is back in pull-up form and can do an impressive number of strict pull-ups... In this episode, Sapna Patel and James Larkin discuss the LEAP 004 and LEAP 003 studies, focusing on the combination of lenvatinib and pembrolizumab in treating melanoma, particularly in patients who are refractory to PD-1 inhibitors. They explore the efficacy, safety, and implications of these studies, as well as the challenges in treatment guidelines and future directions for research in this area. Keywords melanoma, LEAP 004, lenvatinib, pembrolizumab, clinical trials, cancer treatment, efficacy, safety, guidelines Takeaways The LEAP 004 study showed a 21.4% response rate. Lenvatinib is a multi-targeted VEGF receptor inhibitor with potential in melanoma. The combination of lenvatinib and pembrolizumab may increase sensitivity to PD-1 inhibitors. Toxicity is a significant concern with the lenvatinib and pembrolizumab combination. LEAP 003 did not demonstrate an improvement in overall survival compared to pembrolizumab alone. The efficacy of lenvatinib in melanoma is still being evaluated in refractory settings. There is a need for further studies to understand the mechanisms of resistance to PD-1 therapy. Guidelines for treatment may vary significantly between jurisdictions. Patient perspectives on treatment and toxicity are crucial in clinical practice. The future of lenvatinib and pembrolizumab in melanoma treatment remains uncertain. Sound Bites "What's your number of kilos you're deadlifting?" "Lenvatinib has been around for a while." "The unmet need we all know, which is anti PD-1 refractory melanoma." Chapters 00:00 Introduction and Discussion of Deadlifting 03:31 Overview of Leap004 Study and Rationale for Lenvatinib 09:22 Promising Results in Leap004 Study 15:59 Discontinuation of Leap003 Trial 19:33 Challenges with Dosing and Toxicity of Lenvatinib 22:00 Uncertainty in the Use of Lenvatinib-Pembrolizumab in PD-1 Refractory Patients