Pfizer has been counting on a new approval for Sutent, its kidney cancer drug, but an FDA advisory panel isn’t so sure—and the disappointing committee vote was the drug’s second letdown in a month.
The agency’s Oncologic Drug Advisory Committee turned in a tie vote of 6-6 this week on expanding Sutent use into patients who’ve had a cancerous kidney removed and are at high risk of a recurrence.
The vote isn’t binding on the agency, so the FDA could still give its blessing. But the setback comes as Bristol-Myers Squibb is potentially pursuing an approval for its immunotherapies, Opdivo combined with Yervoy, in previously untreated kidney cancer—Sutent’s current bread and butter—and posting head-to-head data against Sutent to support it.
At the European Society of Medical Oncology meeting this month, Bristol-Myers rolled out details of its Checkmate-214 study showing Opdivo beating Sutent by a healthy margin at prolonging the lives of patients with a poor prognosis.
Pfizer would like to stay ahead of its competitors by notching up another approval in a group where Opdivo and Yervoy haven’t yet trod. Sutent could certainly use the jolt; it's still a blockbuster, but in 2016, revenues were down slightly at $1.09 billion, compared with $1.12 billion in 2015, a result that fell short of analyst expectations.
Plus, the treatment paradigm for post-surgery patients is now “suboptimal,” Pfizer says. It’s essentially no treatment at all; patients are observed for a return of the cancer, the company said Tuesday, rather than actively treated to prevent a recurrence, the company says.
And Sutent did deliver results in those patients. In a test against placebo, Sutent patients lived more than a year longer without a recurrence. At the median, Sutent patients treated for one year had held off a relapse by 6.8 years, compared with 5.6 years for placebo.
When that data was released last year, Pfizer’s oncology development chief, Mace Rothenberg, called the results “pretty significant, when you think about disease-free survival being improved by more than a year.”
The study, dubbed S-Trac, was the first positive adjuvant renal cell cancer trial ever, he said in the interview. “This, I think, is a very important, really paradigm-changing, treatment-changing trial for these patients,” he said.
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But as the advisory panel pointed out, Sutent patients were three times as likely to suffer serious side effects. More than 60% of the patients in the Sutent arm reported side effects of grade 3 or above, compared with 21% of placebo patients.
Plus, the panel wasn’t convinced that the disease-free survival advantage was convincing enough—or that treating patients up-front with Sutent was really any better than treating them after the cancer returned.
“The signal wasn’t very clear, and I struggled with the robustness of the data,” Susan Halabi, PhD, professor in the department of biostatistics and bioinformatics at Duke University Medical Center, who voted against approval, said during the meeting, as quoted by Healio. Lance C. Pagliaro, professor of oncology at Mayo Clinic, also cast a dissenting vote. “It’s a year of sunitinib now to avoid a year of sunitinib later,” he said. “I don’t see the net benefit in terms of burden and the number of patient-years to get treatment to [achieve] the same end result.”
The FDA’s decision on that potential change is due in January.
Meanwhile, Opdivo and Yervoy are pressing Sutent in previously untreated patients amid an overall push to bring immunotherapy to cancer patients early on. Right now, Opdivo is approved to treat patients when their cancer returns after a first round of treatment.
The new data shows Opdivo cut the risk of death by 37% in patients at intermediate-to-poor risk, compared with Sutent. The trial patients had clinical characteristics that made them less likely to respond to Sutent therapy.
Sutent is an older drug, and Pfizer has a follow-up—Inlyta—that it’s also testing in post-surgery patients, alongside Merck’s Keytruda and Pfizer’s own Xalkori. That phase 3 trial is ongoing. Inlyta is also in a phase 3 first-line kidney cancer trial, combined with Pfizer and Merck KGaA’s Bavencio, a direct rival to Opdivo. If Inlyta is successful in the post-surgery setting, it could be administered for up to three years, because its side-effect profile is better, Rothenberg said.
And Inlyta has bested Opdivo in one setting: The National Institute for Health and Care Excellence. England's cost-effectiveness watchdogs turned back Opdivo in kidney cancer last year, favoring the Pfizer med instead.