Dr Merchan on Key Data Supporting Pembrolizumab-Based Regimens in Advanced RCC

Jaime R. Merchán, MD, associate professor, medicine, Department of Medicine, Division of Medical Oncology, co-leader, Translational and Clinical Oncology Research Program, director, Phase 1 Clinical Trials Program, Sylvester Comprehensive Cancer Center, the University of Miami Health System, discusses key data supporting the role of pembrolizumab (Keytruda) plus axitinib (Inlyta) or lenvatinib (Lenvima) as a standard-of-care regimen for patients with previously untreated advanced renal cell carcinoma (RCC).

Immuno-oncology (IO) and targeted therapy combinations continue to show efficacy in both clear cell RCC (ccRCC) and non-ccRCC, Merchán begins. Two pivotal trials that support the use of pembrolizumab-based regimens in RCC are the phase 3 CLEAR (NCT02811861) and KEYNOTE-426 (NCT02853331) trials.

In the CLEAR trial, the combination of pembrolizumab and lenvatinib demonstrated high response rates in patients with advanced RCC, Merchán reports. Recent extended follow-up data presented at the 2023 Genitourinary Cancers Symposium further highlighted the efficacy of lenvatinib plus pembrolizumab in this patient population. Notably, improvements in progression-free survival (PFS), overall survival (OS), and objective response rate (ORR) were observed across all patients, regardless of baseline tumor size. Patients with a high tumor burden experienced a median OS of 39.5 months(95% CI, 32.1-48.7), indicating substantial benefit from the combination therapy. Moreover, the data revealed that OS rates improved as tumor volume decreased, with 3-year OS rates ranging from 55.6% in the highest burden subgroup to 73.0% in the lowest burden subgroup. In the final prespecified analysis, the regimen also elicited an 18.3% complete response rate vs 4.8% with sunitinib, further highlighting its efficacy across different RCC subtypes.

Pembrolizumab plus axitinib was evaluated in the randomized KEYNOTE-426 trial, which compared this combination with sunitinib monotherapy in treatment-naive patients with stage IV ccRCC, Merchán continues. Data from the trial's first interim analysis showed significant improvements in PFS, OS, and ORR with pembrolizumab plus axitinib compared with sunitinib. The regimen generated an ORR of approximately 60%, further supporting its efficacy in patients with advanced RCC. In April 2019, pembrolizumab plus axitinib gained FDA approval for patients with advanced RCC based on these results.