ESMO: Bristol Myers' Opdivo racks up GI cancer data for 2 potentially practice-changing FDA nods

Gastrointestinal cancers are stubborn, as plenty of oncology drugmakers know. But Bristol Myers Squibb’s immunotherapy Opdivo has broken through with a couple of potentially practice-changing trials that not only set it up for new FDA approvals, but counter some recent failures for its I-O rivals.

Opdivo topped placebo in post-surgery patients with esophageal cancer, fending off a recurrence for almost two years, according to data presented Monday during the European Society of Medical Oncology virtual meeting.

And, in a separate trial presentation, the PD-1 checkpoint inhibitor plus chemotherapy topped solo chemo at staving off progression in previously untreated patients with esophageal or gastric tumors that can’t be surgically removed—and helping them live longer, too.

The data from these two trials “have the potential to change the standard of care in both adjuvant as well as metastatic cancer,” Bristol Myers Chief Medical Officer Samit Hirawat said ahead of the data release.

No drug is approved to treat esophageal cancer patients who’ve had chemoradiotherapy and then surgery—the current standard approach, Hirawat pointed out. Right now, the strategy is “watch and wait.” But in the Checkmate-577 trial posted Monday, Opdivo doubled the time to cancer’s return to 22.4 months, compared with 11 months in placebo patients, and the results applied regardless of patients’ PD-L1 biomarker status.

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That’s especially good news for the 70% to 75% of esophageal cancer patients who don’t see a complete response after surgery, as lead investigator Ronan Kelly, M.D., director of the Charles A. Sammons Cancer Center at Baylor University Medical Center, pointed out in a release. And for Opdivo itself, it’s the second win in adjuvant patients after its original victory in post-surgery melanoma patients.

The results are “very important” for patients, Hirawat said. They’ve “gone through quite difficult surgery,” and it generally isn’t long before their cancers progress again. With Opdivo, they’re “almost getting to the two-year time point” without a recurrence.

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The survival advantage wasn’t quite as dramatic in the Checkmate-649 trial, but the patients involved couldn’t have their cancers removed with surgery, and their disease was already advanced or spread through the body. And the data were mature enough to show that Opdivo plus chemo actually helped patients live longer. Patients with PD-L1 levels of at least 5% who took the combo lived a median 14.4 months, compared with 11.1 months for chemo—a 29% reduction in the risk of death for a group that’s very tough to treat.

The combo also kept cancer progression at bay for 7.7 months, compared with six months among those taking chemo alone.

Combo patients with lower levels of PD-L1 also benefited, living a median 14 months compared with 11.3 months for chemo patients—a 23% reduction in death risk.

The results were enough to send BMS to the FDA for a potential filing this year, which could yield a first-in-class nod.

RELATED: ESMO: Merck's Keytruda pushes for second esophageal cancer nod with first-line survival win

Opdivo archrival Keytruda, from Merck & Co., has had mixed results in GI cancers. In a similar first-line trial last year, Keytruda plus chemo flopped, failing to help patients with advanced gastric or gastroesophageal junction cancer whose tumors bore biomarker PD-L1. The megablockbuster fell short both in terms of extending patients’ lives and keeping cancer at bay.

But Merck rolled out first-line data in esophageal cancer patients Monday showing Keytruda plus chemo cut the risk of death by 27% in patients regardless of PD-L1 status and 38% of those who tested positive for PD-L1. The results were even better in patients with the squamous form of the disease.

Of course, the results aren’t directly comparable—for one thing, Merck’s PD-L1 threshold was 10% where BMS’ was 5%. But, most importantly, the Opdivo trial included patients with gastric cancer as well as esophageal disease.

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GI cancer overall has proven tough to crack for the I-O field. In 2017, Keytruda failed to extend the lives of second-line patients with PD-L1-positive gastric cancer. Then, last year, Merck posted a failure in the Keynote-062 study, which served as a confirmatory trial to Keytruda’s third-line gastric cancer OK, which was restricted to those bearing the PD-L1 biomarker.

And last year, Pfizer and Merck KGaA’s Bavencio failed as a maintenance therapy, where it couldn’t beat continuing chemo or best supportive care at extending the lives of patients with advanced stomach cancer after one round of successful chemo.

Editor's note: This story was updated to correct the name of the Checkmate-649 trial.