Bristol-Myers Squibb already has an Opdivo combo approved for kidney cancer, but it goes for a new one – and new test data presented on Saturday may just be the ticket, not just to win an FDA approval, but to stack up against their immune system -oncological competitors.
In previously untreated kidney cell cancer, Opdivo plus Cabometyx, Exelixis’ tyrosine kinase inhibitor, reduced the risk of death by 40% compared to Pfizer’s previous standard of care, Sutent. The results applied to all trial patients, not just the PD-L1-positive patients who tend to benefit most from checkpoint inhibitors.
Patients on the cocktail also lived more than twice as long without developing their cancer ̵
In addition, twice as many Opdivo-Cabometyx patients responded and the responses were long-lasting. Where 27% of the trial patients saw results from Sutent, 56% benefited from the Opdivo pairing and the combination patients still responded for 20.2 months at the median, compared with 11.5 months for the Sutent patients.
The results prompted Bristol Myers to talk about a potential FDA approval – and advocate early use of combination therapies.
The results from 9ER show that “the best therapies should be used instead of waiting for later use”, says Bristol Myers CMO Samit Hirawat.
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But will they be enough to compete with Merck’s own IO-TKI pairing? The company’s rival PD-1 inhibitor Keytruda plus Pfizer’s TKI drug Inlyta reduced the risk of death by 46% in PD-L1-positive patients and 41% in patients who did not test positive for the biomarker. And when the Keytruda-Inlyta pairing won FDA approval last year, analysts suggested that similar combinations would need to clear a high bar to gain market share.
Checkmate 9ER study author Toni Choueiri, MD, of the Dana-Farber Cancer Institute, said the Opdivo-Cabometyx combination effect and response rate are impressive, but what can differentiate it is tolerability.
“The different combination therapies are unlikely to be compared,” Choueiri said in a release, “but I think the quality of life may differ on the new treatment, as there was a statistical significance that favored the combination arm with both questionnaires we used.”
But a cancer expert who is not connected to the study said that the jury is still out on IO-TKI combinations versus IO combinations – such as pairing Opdivo with Bristol’s own Yervoy, which has its own benefits for some patients.
“[T]his medical community is divided on whether two immunotherapies or immunotherapy plus an antiangiogenic drug is the better choice, as the different combinations seem to have similar efficacy, says Dominik Berthold, MD, who heads the urological cancer clinic at Lausanne University Hospital. in Switzerland.
And unlike the combinations that are newer on stage, Opdivo-Yervoy has years of study to its credit. As Hirawat pointed out, long-term data now available to the duo show that they still benefit.
RELATED: Bristol-Myers Opdivo-Yervoy duo catches fast FDA nod in first-line kidney cancer
“More than half of the patients treated with that combination live to be four years old,” Hirawat said.
The conclusion, Hirawat pointed out, is that the Opdivo-Yervoy combination has its place – it is FDA-approved especially for middle- and high-risk patients – and Checkmate 9ER shows that Opdivo-Cabometyx has its own, with the benefits in patients regardless of PD-L1 status and regardless risk attributes.
And in both cases, dual therapies should really be standard for first-line patient care, Hirawat argued. Even now, they are still being treated with “individual agent TKIs,” he said, “and the question is why. Dual therapies prove to be better than mono.
Doctors should use “the best treatment first,” Hirawat added. “And we believe that Opdivo-based regimens are best for first-line treatment.”