ESMO: Bristol Myers preps 2nd kidney cancer combo nod as Opdivo-Cabometyx duo slashes death risk 40%

Samit Hirawat
The Checkmate 9ER results show “the best therapies should be used up front rather than waited on for later use,” Bristol Myers Squibb Chief Medical Officer Samit Hirawat said in an interview. (Bristol Myers)

Bristol Myers Squibb already has one Opdivo combo approved in kidney cancer, but it’s going for another—and new trial data presented Saturday could be just the ticket, not only for winning an FDA approval, but for stacking up against its immuno-oncology rivals.

In previously untreated renal cell carcinoma, Opdivo plus Cabometyx, the Exelixis tyrosine kinase inhibitor (TKI), slashed the risk of death by 40% compared with Pfizer’s former standard of care, Sutent. That result applied to all of the trial patients, not just the PD-L1-positive patients that tend to benefit most from checkpoint inhibitors.

Patients on the cocktail also lived more than twice as long without their cancer progressing—16.6 months versus 8.3 months for Sutent patients, according to results from the Checkmate 9ER trial presented at the European Society of Medical Oncology virtual meeting.

Plus, twice as many Opdivo-Cabometyx patients responded, and the responses were long-lasting. Where 27% of trial patients saw results from Sutent, 56% benefited from the Opdivo pairing, and the combo patients were still responding for 20.2 months at the median, compared with 11.5 months for the Sutent patients.

The results had Bristol Myers talking up a potential FDA approval—and advocating early use of combo treatments.

The 9ER results show “the best therapies should be used up front rather than waited on for later use,” Bristol Myers Chief Medical Officer Samit Hirawat said.

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But will they be enough to compete with Merck’s own I-O/TKI pairing? The company’s rival PD-1 inhibitor Keytruda plus Pfizer’s TKI drug Inlyta cut the risk of death by 46% in PD-L1-positive patients and 41% in patients who didn’t test positive for the biomarker. And, when the Keytruda-Inlyta pairing won FDA approval last year, analysts suggested that similar combos would have to clear a high bar to grab market share.

Checkmate 9ER study author Toni Choueiri, M.D., of Dana-Farber Cancer Institute, said the Opdivo-Cabometyx combo’s efficacy and response rate are impressive, but what may set it apart is tolerability.

“The various combination treatments will unlikely be compared head-to-head,” Choueiri said in a release, “but I think quality of life could differentiate this new therapy, as there was a statistical significance favoring the combination arm with both questionnaires we used.”

But a cancer expert not affiliated with the study said the jury is still out on I-O/TKI combos versus I-O combos—such as the pairing of Opdivo with Bristol’s own Yervoy, which boasts its own advantages for some patients.

“[T]he medical community is divided about whether two immunotherapies or immunotherapy plus an anti-angiogenic drug is the better choice, since the different combinations appear to have similar effectiveness,” said Dominik Berthold, M.D., who heads up the urological cancers clinic at Lausanne University Hospital in Switzerland.

Unlike the combos that are newer on the scene, Opdivo-Yervoy has years of study to its credit. As Hirawat pointed out, long-term data now available on that duo show they’re still benefiting.

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“More than half of patients treated with that combo are alive at four years,” Hirawat said.

Bottom line, Hirawat pointed out, the Opdivo-Yervoy combo has its place—it’s FDA-approved specifically for intermediate- and high-risk patients—and Checkmate 9ER shows Opdivo-Cabometyx has its own, with its benefits in patients regardless of PD-L1 status and regardless of risk attributes.

And in both cases, dual therapies really should be standard of care for first-line patients, Hirawat maintained. Even now, they’re still being treated with “single-agent TKIs,” he said, “and the question is why. Dual therapies are shown to be better than mono."

Physicians should be using “the best therapy first,” Hirawat added. “And we believe Opdivo-based regimens are best for first-line treatment.”