Combination of nivolumab and cabozantinib found to significantly improve progression-free survival and reduced the risk of death versus sunitinib in previously untreated patients with advanced kidney cancer

An immunotherapy agent combined with a tyrosine kinase inhibitor drug whose clinical testing as a first-line treatment in advanced kidney cancer was led by Toni K. Choueiri, MD, Director of the Lank Center for Genitourinary Oncology at Dana-Farber Cancer Institute, has become a standard therapy.

The combination of nivolumab (OPDIVO®) and cabozantinib (CABOMETYX®) was approved today by the U.S. Food and Drug Administration (FDA) as a first-line treatment for patients with advanced renal cell carcinoma (RCC). The approval is based on results from CheckMate -9ER, a phase 3 trial evaluating the combination compared to sunitinib, a single agent treatment.

The study found the combination significantly improved responses, progression-free survival and reduced the risk of death when compared to sunitinib in previously untreated patients with advanced kidney cancer. These results were first presented in a Presidential/Plenary Symposium of the European Society for Medical Oncology (ESMO) Virtual Congress 2020.

“I’m quite encouraged with the results,” said Choueiri, the Jerome and Nancy Kohlberg Professor of Medicine at Harvard Medical School. “The combination treatment demonstrated meaningful efficacy benefits with consistent effects observed across pre-specified subgroups. These results, along with manageable toxicity and superior health-related quality-of-life, highlight this regimen’s potential importance among first-line combinations of immunotherapies and tyrosine kinase inhibitors.”

Nivolumab is a PD-1 checkpoint inhibitor designed to help the body’s immune system recognize and attack cancer cells. Cabozantinib is a small-molecule inhibitor of tyrosine kinases including c-Met, AXL and VEGFR2, which are implicated in cancer cell growth. Cabozantinib may also counteract tumor-induced immunosuppression, say the investigators.

The CheckMate -9ER trial randomized 651 patients, testing the combination against sunitinib. The data showed that the combination of nivolumab and cabozantinib reduced the risk of death by 40% compared with sunitinib. Median overall survival was not reached in either group, at a median follow-up of 18.1 months. In patients receiving the combination, median progression-free survival – the study’s primary endpoint – was doubled compared to those who got sunitinib alone, 16.6 months vs 8.3 months. The median duration of response was 20.2 months for the combination, vs 11.5 months for sunitinib.

In addition, twice as many patients receiving the combination had a response compared to sunitinib – 56% vs. 27% – and 8% achieved a complete response vs 5% for sunitinib.

The combination side effects were manageable according to the investigators with less than 6% of patients having to completely discontinue both nivolumab and cabozantinib due to side effects. Patients treated with nivolumab plus cabozantinib reported significantly better health-related quality of life than those treated with sunitinib at most time points, according to a kidney symptom index.

Nivolumab and cabozantinib have each previously been approved by the FDA in certain patients with advanced kidney cancer, but now with this FDA approval, the combination can be used as an initial treatment in this patient group.

“This is a pivotal study,” said Choueiri. “This drug combination approval means our patients presenting with metastatic renal cell cancer have another therapeutic option.”

This work was supported in part by Bristol Myers Squibb and Ono Pharmaceutical Co. and co-funded by Exelixis, Ipsen and Takeda Pharmaceutical Company Limited. Choueiri is supported in part (institutional funds) by the Jerome and Nancy Kohlberg Chair at Harvard Medical School. Choueiri’s disclosures include receiving research funds from AstraZeneca, Bayer, BMS, Cerulean, Eisai, Foundation Medicine Inc., Exelixis, Ipsen, Tracon, Genentech, Roche, Roche Products Limited, GlaxoSmithKline, Merck, Novartis, Peloton, Pfizer, Prometheus Labs, Corvus, Calithera, Analysis Group, Takeda. T. as well as a consulting or advisory role for AstraZeneca, Alexion, Sanofi/Aventis, Bayer, BMS, Cerulean, Eisai, Foundation Medicine Inc., Exelixis, Genentech, Heron Therapeutics, Roche, GlaxoSmithKline, Merck, Novartis, Peloton, Pfizer, EMD Serono, Prometheus Labs, Corvus, Ipsen, Up-to-Date, NCCN, Analysis Group.