Dr Merchán on the Role of Immunotherapy and TKI Combinations in RCC

Jaime R. Merchán, MD, professor, co-leader, Translational and Clinical Oncology Research Program, director, Phase 1 Clinical Trials Program, Department of Medicine, Division of Medical Oncology, the University of Miami Miller School of Medicine, Sylvester Comprehensive Cancer Center, discusses the current roles for immunotherapy and TKI combination regimens in the management ofrenal cell carcinoma (RCC).

The use of TKIs and immunotherapy for patients with metastatic RCC has changed over the past several years, Merchán says. Ongoing research often generates potent, effective combination regimens for patients in this population, Merchán notes.

For patients with clear cell RCC (ccRCC), FDA-approved frontline immunotherapy and TKI combinations include: pembrolizumab (Keytruda) plus lenvatinib (Lenvima), nivolumab (Opdivo) plus cabozantinib (Cabometyx), and avelumab (Bavencio) plus axitinib (Inlyta), Merchán explains. Each of these combinations is associated with favorable efficacy compared with single-agent TKIs, Merchán emphasizes.

Pembrolizumab plus lenvatinib was approved in 2021 for patients with previously untreated advanced RCC based on findings from the phase 3 CLEAR/KEYNOTE-581 trial (NCT02811861), in which the combination elicited a median progression-free survival (PFS) of 23.9 months (95% CI, 20.8-27.7) compared with 9.2 months (95% CI, 6.0-11.0) in patients who received sunitinib (HR, 0.39; 95% CI, 0.32-0.49; P < .0001).

The combination of nivolumab and cabozantinib received approval in 2021 for patients with advanced disease. This regulatory decision was supported by findings from the phase 3 CheckMate-9ER trial (NCT03141177), which demonstrated a median PFS of 16.6 months with nivolumab plus cabozantinib vs 8.3 months with sunitinib (Sutent; HR, 0.51; 95% CI, 0.41-0.64; P < .0001).

Avelumab plus axitinib was approved in 2019 for patients with advanced ccRCC based on data from the phase 3 JAVELIN Renal 101 trial (NCT02684006), in which the combination induced a median PFS of 13.8 months (95% CI, 11.1-not evaluable) vs 8.4 months (95% CI, 6.9-11.1) with sunitinib (HR, 0.69; 95% CI, 0.563-0.840; 2-sided P = .0002).

As immunotherapy and TKI combination regimens continue to drive progress in the management of ccRCC, they are also evolving for patients with non-ccRCC, Merchán notes. Non-ccRCC, which is rarer than ccRCC, is considered an orphan disease that has historically lacked standard treatments, Merchán concludes.