Dr Vaishampayan on the Impact of TKI Combination Therapies in the Treatment of RCC

Ulka Nitin Vaishampayan, MBBS, director, the Phase I Program at Rogel Cancer Center, professor of internal medicine, University of Michigan, discusses updated data for frontline TKI combination therapies in the treatment of patients with metastatic renal cell carcinoma (RCC).

At an OncLive® State of the Science Summit™, Vaishampayan discussed frontline therapy in metastatic RCC and detailed updates presented at the 2023 ASCO Annual Meeting. These updated results included the 5-year analysis of axitinib (Inlyta) plus pembrolizumab (Keytruda) in the phase 3 KEYNOTE-426 (NCT02853331) trial, and the prespecified overall survival (OS) analysis at 4 years of follow-up for lenvatinib (Lenvima) plus pembrolizumab in the phase 3 CLEAR trial (NCT02811861).

Sunitinib (Sutent) monotherapy served as the control arm in both of these studies, and the survival improvement vs sunitinib remained consistent for both combinations, Vaishampayan expands. In KEYNOTE-426, pembrolizumab plus axitinib elicited a median OS of 47.2 months (95% CI, 43.6-54.8) compared with 40.8 months (95% CI, 34.3-47.5) for sunitinib (HR, 0.84; 95% CI, 0.71-0.99). In CLEAR, the median OS was 53.7 months (95% CI, 48.7–not evaluable [NE]) for pembrolizumab plus lenvatinib vs 54.3 months (95% CI, 40.9-NE) for sunitinib (HR, 0.79; 95% CI, 0.63-0.99; P = .0424).

Moreover, the progression-free survival (PFS) continued to be superior with the combination therapies vs sunitinb, she says. For KEYNOTE-426, the median PFS was 15.7 months (95% CI, 13.6-20.2) for pembrolizumab plus axitinib vs 11.1 months (95% CI, 8.9-12.5) for sunitinib (HR, 0.69; 95% CI, 0.59-0.81). In CLEAR, the median PFS was 23.9 months (95% CI, 20.8-27.7) for pembrolizumab plus lenvatinib compared with 9.2 months (95% CI, 6.0-11.0) for sunitinib (HR, -.47; 95% CI, 0.38-0.57; P < .0001)

The other intriguing aspect to emerge from KEYNOTE-426 study was that 62.2% of patients in the experimental arm who discontinued treatment went on to receive subsequent therapy. A previous analysis of patients in the International Metastatic RCC Database Consortium showed that approximately only half of patients were able to proceed to second-line therapy, Vaishampayan continues. Being able to put more patients in position to receive subsequent therapy would serve as a step toward improving outcomes for this patient population, Vaishampayan concludes.