Weighing Response, Survival, and Toxicity After LEAP-010

Ross Merkin, MD, examines why a higher tumor response rate does not always translate into longer survival, a long-standing pattern in oncology. He explains that the oncology community, with regulatory guidance, considers improved overall survival one of the most important benefits a therapy can offer. In the phase 3 LEAP-010 trial, a pembrolizumab-based combination improved objective response rate and progression-free survival without improving overall survival, and it increased toxicity. Dr. Merkin stresses that a new first-line regimen must show improvement over the current standard of pembrolizumab alone or with chemotherapy. He asks whether toxicity limited drug exposure or tumors developed resistance too quickly, and he calls for paired translational research. Will Ince, MRCP, FRCR, says symptomatic patients with a high disease burden need deep responses, and a durable response that improves symptoms is a win-win. Kevin Harrington, MBBS, PhD, FRCP, FRCR, adds that deeper responses bring better symptom relief and probably longer survival.