Dr Matrana on the Importance of Combination Therapies in Metastatic RCC

“For the first time in history with these combinations, I have the advantage of being able to tell a patient, ‘Yes, we have a combination therapy—an option for you that has a 90% to 95% chance of at least stabilizing your disease and essentially working for you.’ That's a really good feeling to have.”

Marc R. Matrana, MD, professor of internal medicine at The University of Queensland Medical School – Ochsner Health and a medical oncologist at Ochsner MD Anderson Cancer Center, emphasized the importance of having combination therapy options for the first-line treatment of advanced or metastatic renal cell carcinoma (RCC).

Results from the phase 3 KEYNOTE-426 trial (NCT02853331), which evaluated pembrolizumab (Keytruda) plus axitinib (Inlyta) as first-line therapy for patients with advanced clear cell RCC (ccRCC), demonstrated that 60-month overall survival (OS) rates were 41.9% for those given the combination compared with 37.1% in patients treated with sunitinib (Sutent). Of note, the 60-month progression-free survival (PFS) rates were 18.3% vs 7.3% in the pembrolizumab/axitinib vs sunitinib arms, respectively.

Discussions about first-line therapy options and disease control rates are essential for patients with newly diagnosed metastatic RCC, Matrana began. Historically, there were not many combination therapies for kidney cancer, particularly in the first-line setting for advanced or metastatic disease, he noted. However, based on data from the KEYNOTE-426 study, he underscored the importance of having this option and others for respective patients, especially one that could help with disease control.

Having access to combination therapies in the first-line setting, such as pembrolizumab/axitinib, has paved the way for additional modalities to control disease, which is a good feeling to have, Matrana said.

The study included patients with confirmed locally advanced or metastatic ccRCC with or without sarcomatoid features, who did not previously receive systemic therapy for their metastatic disease. Patients were also required to have a Karnofsky performance status of 70% or greater and 1 or more measurable lesions per RECIST 1.1 criteria. Among the 861 patients enrolled on the study, 432 were randomly assigned to the pembrolizumab/axitinib arm and 429 were randomly assigned to the sunitinib arm. Those treated with pembrolizumab/axitinib received 200 mg of intravenous pembrolizumab every 3 weeks for 35 doses with oral axitinib at 5 mg twice daily. Patients in the sunitinib arm received 50 mg of oral sunitinib once daily on a 4-week on, 2-week off schedule. Data from this study supported the April 2019 approval of pembrolizumab plus axitinib for the first-line treatment of patients with advanced RCC.