Dr Rini on the Background of a Biomarker Analysis of KEYNOTE-426 in RCC

Brian I. Rini, MD, FASCO, Ingram Professor of Medicine, Department of Medicine, Division of Hematology Oncology, Vanderbilt University; chief, Clinical Trials, Vanderbilt-Ingram Cancer Center, discusses the background of analyzing clustering from the phase 3 KEYNOTE-426 study (NCT02853331) investigating pembrolizumab (Keytruda) plus axitinib (Inlyta) vs sunitinib (Sutent) for the first-line treatment of patients with advanced renal cell carcinoma (RCC). Rini also highlights the importance of biomarker-informed treatment. Notably, data from this analysis of the KEYNOTE-426 study were shared at the 2024 ASCO Annual Meeting.

KEYNOTE-426 investigated frontline treatment for clear cell kidney cancer, specifically focusing on patients with metastatic disease, Rini begins. This trial was one of the pivotal registrational trials for pembrolizumab plus axitinib, which has since become a standard-of-care (SOC) regimen for patients with advanced RCC. Patients were randomized to receive either this combination therapy or sunitinib, he explains. Data from KEYNOTE-426 have consistently demonstrated the benefits of the combination therapy vs sunitinib in terms of overall survival, progression-free survival, overallresponse rate, and complete response rate, thereby reaffirming its status as the SOC, Rini reports.

At the 2024 ASCO Annual Meeting, investigators presented findings from a biomarker analysis ofpatients enrolled in the KEYNOTE-426 trial, he continues. Biomarkers are critical in the context of kidney cancer, where there has been limited success in developing reliable biomarkers that can guide the selection of individual therapies for patients. Currently, 4 immune-based therapies areapproved for the treatment of patients with kidney cancer that offer a survival advantage, he explains. Oncologists often base their treatment choices on factors such as personal preference, patient comorbidities, response durability, and toxicity profiles, rather than on individual patient biology, Rini notes.

The goal behind biomarker research efforts is to develop markers that can help tailor treatments to the specific biological characteristics of each patient, Rini expands. The biomarker analysis presented at ASCO represents one of the first significant steps toward achieving this goal, he states. By identifying biomarkers that can predict which patients will benefit most from certain therapies, the RCC field aims to move closer to personalized kidney cancer treatment, Rini concludes.