Opdivo-Yervoy Combo Showing Durable Benefits in Untreated Kidney Cancers in Long-term Trial

Opdivo-Yervoy Combo Showing Durable Benefits in Untreated Kidney Cancers in Long-term Trial

A combination of two immune checkpoint inhibitors, Opdivo (nivolumab) and Yervoy (ipilimumab), continues to significantly extend the lives of people newly diagnosed with advanced renal cell carcinoma (RCC) compared to standard of care, updated results from a long-term Phase 3 trial show.

The combination was seen to work well across the trial’s overall population, lowering by 28% patients’ risk of death  compared to standard care — Sutent (sunitinib). And it did particularly well in a group of patients with intermediate- and high-risk disease, who had a 34% reduction in that risk.

These findings, at nearly four years of follow-up, support the continued use of the Opdivo-Yervoy combo in this subset of kidney cancer patients with a poorer prognosis, for whom the combination is approved both in the U.S. and in Europe.

Trial results were recently shared at the American Society of Clinical Oncology (ASCO) 2020 Genitourinary Cancers Symposium in San Francisco, in the oral presentation, “Overall survival and independent review of response in CheckMate 214 with 42-month follow-up: First-line nivolumab + ipilimumab (N+I) versus sunitinib (S) in patients (pts) with advanced renal cell carcinoma (aRCC).”

“Results from this 42-month follow-up from the CheckMate -214 study reinforce the previously observed findings … that [Opdivo] plus [Yervoy] has the potential to significantly improve long-term survival for patients with advanced renal cell carcinoma, a population with high unmet needs,” Nizar M. Tannir, MD, a trial investigator at The University of Texas MD Anderson Cancer Center, said in a press release.

Opdivo and Yervoy — both sold by Bristol-Myers Squibb — are two immune checkpoint inhibitors that work by blocking proteins used by cancer cells to evade the immune system. Opdivo targets the PD-L1 protein on cancer cells, and Yervoy targets the CTLA-4 protein on T-cells — immune cells with the ability to fight tumors.

A combination of Opdivo plus low-dose Yervoy is currently approved for advanced colorectal cancer, and is being reviewed by the U.S. Food and Drug Administration (FDA) for people with untreated lung cancer.

This combination is also approved as a first-line treatment for people with intermediate and high-risk advanced renal cell carcinoma — the most common type of kidney cancer — based on findings from the long-term Phase 3 CheckMate-214 trial (NCT02231749).

CheckMate-214 includes 1,096 patients — 847 with intermediate or high risk — who were randomly assigned to either four doses of Opdivo at 3 mg/kg plus 1 mg/kg of Yervoy given as an infusion every three weeks, followed by Opdivo every two weeks thereafter. Or they were assigned to Sutent, given once daily in a four weeks on, two weeks off, regimen.

Treatment continued until patients experienced disease progression or developed signs of unacceptable toxicity.

This trial’s main goals are to determine if the combination extended overall survival compared to Sutent, extended the time patients lived without disease progression, and increased patient responses in the intermediate- to high-risk group. Secondary goals include similar assessments in the overall population.

The combo’s approval was based on data collected after a median follow-up of 25.2 months, at which point the combination significantly reduced the risk of death (by 37%), lowered the risk of disease progression or death (by 18%), and increased responses (42% vs. 27% for Sutent) in the population with a poorer prognosis compared with Sutent.

Updated results presented at the ASCO symposium, corresponding to at least 42 months (3.5 years) of follow-up, continue to demonstrate the benefits of Opdivo plus Yervoy in this patient population.

It was seen to reduce the risk of death by 34%, with more than half of patients (52%) with intermediate and high risk in the combination arm alive at data cut-off, compared to 39% of those given Sutent.

These immunotherapies also increased the number of these at-risk patients responding to treatment (42% vs. 26%), including the number of complete responses (10% vs. 1%). Response also lasted longer in people on the combo treatment, with more than half still responding at the time of the analysis, compared to a median response duration of 19.7 months for Sutent.

Across the overall population, Opdivo and Yervoy also demonstrated significant benefits, although not as striking as in patients with a poorer prognosis.

The 42-month overall survival rate for Opdivo plus Yervoy was 56% and 47% for those on Sutent, representing a 28% reduction in the risk of death.

Responses were seen in 39% of patients given the combination, and were ongoing in more than half of them, while 33% of patients responded to Sutent for a median of 24.8 months. Complete responses were also better with immunotherapy — 11% vs. 2%.

Regarding safety, the incidence severe and life-threatening adverse events related to treatment was consistent with what has been reported earlier. No trial patient died due to treatment-related adverse events.

“These positive findings from CheckMate -214 continue to demonstrate the complementary nature of dual immuno-therapy and reinforce the depth and durability of response the combination of Opdivo plus Yervoy can deliver for patients,” said Brian Lamon, PhD, development lead, genitourinary cancers, at Bristol-Myers Squibb.

“We look forward to continuing to explore the potential that this combination holds for patients with difficult-to-treat cancers.”