Dr Braun on Selecting Immune Checkpoint Inhibitor–Based Combos in ccRCC

David Braun, MD, PhD, assistant professor of medicine (Medical Oncology), member, Center of Molecular and Cellular Oncology (CMCO), Yale Cancer Center, discusses considerations around the use of different combinations utilizing immune checkpoint inhibitors for the treatment of patients with clear cell renal cell carcinoma (ccRCC).

Immune checkpoint inhibitors form the backbone of first-line therapy for patients with advanced disease that cannot be treated with surgery alone, Braun begins. Notably, these types agents have more recently integrated as adjuvant therapy for patients with high-risk resected disease. For example, in November 2021, the FDA approved pembrolizumab (Keytruda) for the adjuvant treatment of patients with RCC at intermediate-high or high risk of recurrence following nephrectomy, or following nephrectomy and resection of metastatic lesions.

In the advanced disease metastatic disease setting, where the cancer can't be treated with surgery alone, immunotherapy-based combinations are considered, Braun says. These combinations can utilize immune checkpoint inhibitors in two different ways, he continues. One type of combination features two immune-oncology (IO) agents targeting PD-1 and CTLA-4—nivolumab (Opdivo) plus ipilimumab (Yervoy). The other option is an immunotherapy combined with a TKI—including pembrolizumab plus lenvatinib (Lenvima), nivolumab plus cabozantinib (Cabometyx), and pembrolizumab plus axitinib (Inlyta).

In terms of selecting between an IO-IO or IO-TKI combination for the treatment of patients with advanced disease, Braun explains that there isn't one right answer. These types of combinations have never been compared in head-to-head trials, so there are no prospective data to determine which option is the better choice for a given patient, he says.

Braun notes deciding which immune checkpoint inhibitor–based combination to use should be made on a case-by case basis. Each treatment should be a personalized one, based on the efficacy and safety data of each combination and the disease and patient factors for each individual, he concludes.