Dr Rini on Sustained Survival Outcomes After Completion of Pembrolizumab and Axitinib in ccRCC

Brian I. Rini, MD, FASCO, Ingram Professor of Medicine, Division of Hematology Oncology, chief of Clinical Trials, Vanderbilt-Ingram University Cancer Center, discusses long-term survival outcomes in patients with advanced clear cell renal cell carcinoma (ccRCC) who received frontline pembrolizumab (Keytruda) and axitinib (Inlyta) in the phase 3 KEYNOTE-426 trial (NCT02853331).

The KEYNOTE-426 trial compared the efficacy and safety of pembrolizumab and axitinib with sunitinib (Sutent) monotherapy in patients with newly diagnosed, treatment-naïve stage IV ccRCC. Data from the first interim analysis showed that the doublet significantly improved progression-free survival (PFS), overall survival (OS), and overall response rates (ORR) vs sunitinib. These data supported the regimen's FDA approval for patients with advanced RCC in April 2019.

Investigators presented data from the 5-year analysis of the trial at the 2023 ASCO Annual Meeting. At an extended median follow-up of 42.8 months, the regimen continued to show superior efficacy vs the monotherapy with respect to PFS, OS, and ORR.

The presentation also included an analysis of survival outcomes in complete responders. Of the 432 patients in the doublet arm, 27.8% responded completed all 35 cycles of pembrolizumab, Rini reports.

Patients who responded to initial treatment were more likely to continue therapy at the 2-year mark than those who had stable or progressive disease, Rini continues. The 5-year survival rate in patients who completed all 35 cycles of pembrolizumab was 70.7%, and the median OS was not reached. Additionally, 5-year PFS rate was 32.8%, with a median PFS of 37.4 months.

Although this analysis was conducted in a selected, clinical trial population, the benefit shown with the doublet mirrors the effect seen in community settings, he says. The patients analyzed have similar baseline characteristics to that of the intention-to-treat population, Rini notes. These findings show that patients who respond to the doublet experience sustained benefit for a long period of time, Rini concludes.

Disclosures: Dr Rini disclosed leadership relationships with MashupMD and MJH Life Sciences and stock ownership in PTC Therapeutics. He also has consulting or advisory roles for Alkermes, Aravive, Arrowhead Pharmaceuticals, Athenex, AVEO, Bristol-Myers Squibb, Corvus Pharmaceuticals, Debiopharm Group, Eisai, EUSA Pharma, Genentech, HiberCell, Merck, NiKang Therapeutics, Pfizer, and Surface Oncology. Research funding was received from ADC Therapeutics, Adela, Aravive, Arcus Biosciences, Arrowhead Pharmaceuticals, AstraZeneca/MedImmune, AVEO, Bristol-Myers Squibb, Daiichi Sankyo/UCB Japan, Dracen, Dragonfly Therapeutics, Exelixis, Gilead Sciences, HiberCell, Incyte, Janssen, Merck, Pionyr, Point Therapeutics, Roche/Genentech, Seagen, Stata, Surface Oncology, and Vasgene Therapeutics. Travel expenses were paid by Bristol-Myers Squibb, Merck, and Pfizer.