Bristol Myers' Opdivo wins landmark FDA nod as first I-O therapy for front-line stomach cancer

The stomach cancer field is littered with immunotherapy shipwrecks, but one has now safely sailed past the regulatory finish line.

Bristol Myers Squibb’s Opdivo, used in tandem with chemotherapy, won FDA approval for previously untreated gastric cancer, gastroesophageal junction cancer and esophageal adenocarcinoma that are advanced or spread to other parts of the body. The go-ahead is for all tumors regardless of their expression of the PD-L1 marker.

With Friday’s approval, Opdivo becomes the first immunotherapy for initial treatment of stomach cancer, the FDA noted. And it came after the Opdivo regimen showed it could help those patients live longer—the first drug to do so in more than a decade, Richard Pazdur, M.D., director of the FDA’s Oncology Center of Excellence, said in a statement.

In the CheckMate-649 trial, adding Opdivo to chemotherapy cut the risk of death by 20% in all enrolled patients in the three now FDA-approved indications. Patients who got the Opdivo-chemo combo lived a median 13.8 months, versus 11.6 months for solo chemotherapy. About 70% of all randomized patients had stomach cancer.

The life extension benefit was more pronounced in patients with PD-L1 expression at a combined positive score of at least 5. Among them, the Opdivo-chemo combo pared down the risk of death by 29%, according to data shared at the 2020 meeting of the European Society for Medical Oncology (EMSO).

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“These findings are important, reinforcing the potential of this Opdivo-based combination as a standard of care for this population of patients in high need of treatment options that may extend their lives,” Yelena Janjigian, M.D., the phase 3 trial’s principal investigator, said in a statement.

Stomach cancer is notoriously difficult to treat, even for checkpoint inhibitors, which have made their mark in other cancer types with larger survival benefits. The estimated five-year survival rate for metastatic stomach cancer is merely 6% in the U.S.

Opdivo knows this too well. In fact, the drug failed to significantly extend the lives of previously untreated stomach cancer patients in another pivotal trial Bristol Myers conducted in Asia with Opdvio’s original developer Ono Pharmaceutical. Stomach cancer is much more prevalent in East Asian countries than in North America.

According to data from the Attraction-4 trial, also unveiled at ESMO 2020, the combo of Opdivo and chemo did much better than solo chemo at staving off cancer progression, but it only led to a 10% reduction in death risk. Some participants in that trial were treated with a different chemotherapy from the one used in CheckMate-649.

RELATED: In a first, Merck's Keytruda snags FDA nod for esophageal cancer as stomach cancer label hangs in the balance

Opdivo’s archrival, Merck & Co.’s Keytruda, has also suffered setbacks in stomach cancer. In Keynote-061, solo Keytruda failed to top the widely used chemotherapy paclitaxel in patients who'd already been through one round of treatment. In previously untreated patients, a combination of Keytruda and chemo failed to beat solo chemo at prolonging the lives of patients with stomach cancer or gastroesophageal junction cancer. The cocktail wasn’t strong enough in patients whose tumors expressed PD-L1 or those who expressed the marker at a higher combined positive score of at least 10.

Those two trial flops have now put Keytruda’s conditional FDA nod in third-line stomach cancer in jeopardy amid an industrywide review by the agency. That Keytruda indication, along with several others from PD-1/L1 inhibitors that have failed in confirmatory trials, has become the target of an FDA advisory committee meeting next week.

The FDA reviewed Opdivo’s current front-line nod through Project Orbis, which allows for concurrent submission and review of oncology drugs with other foreign drug agencies. Regulators in Australia, Brazil, Canada and Switzerland are simultaneously evaluating the application.