Dr Lee on Extended Follow-Up With Pembrolizumab and Lenvatinib in Pretreated mRCC

Chung-Han Lee, MD, PhD, a medical oncologist at Memorial Sloan Kettering Cancer Center, discusses the final results of the phase 2 cohort of a phase 1/2 trial (NCT02501096) evaluating lenvatinib (Lenvima) plus pembrolizumab (Keytruda) in patients with pretreated metastatic clear cell renal cell carcinoma (mRCC).

The trial enrolled patients who had progressive disease after treatment with a PD-1/PD-L1-containing therapy. The results, which were presented at the 2023 Kidney Cancer Research Summit, showed that with extended follow-up of 24 months, the combination elicited comparable activity in the treatment-naïve cohort as what has been seen in those enrolled in the pivotal phase 3 CLEAR trial, Lee says. Notably, a subgroup of patients with immune checkpoint inhibitor–pretreated disease also derived durable responses, Lee says.

These results stand in stark contrast to what was reported in the phase 3 CONTACT-03 trial (NCT04338269), which showed that the addition of atezolizumab (Tecentriq) to cabozantinib (Cabometyx) following progression of a PD-1/PD-L1 inhibitor did not improve progression-free survival or overall survival compared with cabozantinib alone in patients with mRCC.

The results from this trial suggest that continued use of a PD-L1 inhibitor in combination with cabozantinib does not have a role in immunotherapy-pretreated RCC, Lee explains. However, results from the phase 2 portion of the aforementioned trial suggest that PD-1 inhibition in combination with a different VEGF TKI, in this case, lenvatinib, may still be useful, Lee explains. Additionally, it remains unknown whether the addition of pembrolizumab provides added activity given the limitations of the trial design, Lee concludes.