Checkpoint Immunotherapy Combination Approved for First-line Treatment of Advanced Kidney Cancer

Immunotherapy is now available as a first-line treatment option for patients with advanced kidney cancer, with today’s FDA approval of the checkpoint immunotherapy combination of nivolumab (Opdivo®) and ipilimumab (Yervoy®), both owned by Bristol-Myers Squibb.

While nivolumab was previously approved as a second-line option for patients with advanced kidney cancer, this announcement marks the first time that these patients will be able to receive immunotherapy without having to first go through chemotherapy.

“This is a major milestone for patients battling advanced kidney cancer. The combination of nivolumab and ipilimumab provided a clear clinically relevant advantage in terms of prolonging the lives of RCC patients over sunitinib, a standard during the past ten-plus years,” said Toni K. Choueiri, MD, the director of the Dana-Farber Cancer Institute's Lank Center for Genitourinary Oncology. “The new combination should be a new standard moving forward in advanced [kidney cancer].”

The approval, which was based on the phase III CheckMate-214 clinical trial, covers patients with intermediate- or poor-risk advanced renal cell carcinoma who are either newly diagnosed or have relapsed after prior surgery. In the trial, 550 patients received the immunotherapy combination—which targets both the PD-1 and CTLA-4 immune checkpoint pathways—and were compared to 546 patients who received the chemotherapy sunitinib (Sutent®, Pfizer), the standard-of-care treatment in this disease setting.

Previously published results from this trial showed that, compared to the standard chemotherapy, patients with who were treated with immunotherapy demonstrated superior overall survival (75% of patients were still alive at 18 months versus 60%), median progression-free survival (11.6 months versus 8.4 months), and response rates (42% versus 27%). Immunotherapy-treated patients also experienced complete responses far more frequently, with 9% having complete tumor regression compared to only 1% of those treated with chemotherapy.

While a higher proportion of the chemotherapy-treated group experienced serious (Grade 3-4) treatment-related adverse events compared to the immunotherapy-treated group, a higher proportion of the patients who received immunotherapy had to discontinue therapy due to the side effects.

Fortunately, this cessation of treatment does not preclude patients from experiencing positive responses to immunotherapy, according to Padmanee Sharma, MD, PhD, a former CRI clinical grantee and one of the oncologists involved in the pivotal CheckMate-214 study.

Furthermore, as these checkpoint immunotherapies have both been in use in the clinic for several years now, oncologists have developed a better grasp of how to address these commonly occurring side effects.

“The patients are educated about the fact that these drugs can cause immune-related adverse events, and so they need to report any changes that occur when they’re on the therapy,” said Sharma. ”They’re the same type of adverse events that we’ve seen before, so we know how to manage them well as long as we can identify them early.” Sharma also pointed out, importantly, that there were no deaths due to treatment.