ESMO: Can Bristol-Myers' Opdivo-Yervoy pairing be 'practice-changing' in first-line NSCLC? Experts disagree

BARCELONA—Merck & Co.’s Keytruda may have the chemo-combo business locked up in previously untreated lung cancer, but Bristol-Myers Squibb figures it has a chance to bring in patients who prefer to skip chemo and use a second immunotherapy instead.

Bristol’s Opdivo-Yervoy pairing helped newly diagnosed patients live longer than chemotherapy alone, the company reported Saturday at the European Society for Medical Oncology Congress. Patients taking the Opdivo-Yervoy combo lived for a median 17.1 months compared with 14.9 months for chemo patients. In other words, it cut the risk of death by 21%.

The combination of Opdivo, a PD-1 checkpoint inhibitor, and Yervoy, which targets CTLA4, shows "the unique features of CTLA4," said Fouad Namouni, head of oncology R&D at Bristol-Myers. The combo delivered "not just good response rates, but more importantly the depth and durability of response," he said.

The two-year survival rate, for instance, was 40% for patients taking the Opdivo-Yervoy combo, whether they tested positive for the PD-L1 biomarker or not. Among the chemo patients, 33% of who expressed PD-L1-survived to the two-year mark, while 23% of the PD-L1-negative patients did.

“In my opinion these data are practice-changing,” lead author Solange Peters said in a statement. “We already have several front-line treatment options for these patients, including chemotherapy combined with an anti-PD1 agent or an anti-PDL1 agent alone. And now we have a chemotherapy-sparing option of nivolumab plus ipilimumab.”

The reduction in death risk didn’t measure up to Keytruda’s chemo-combo results; a combination of Keytruda, Alimta and platinum chemo cut first-line patients’ risk of death by half. And in a surprise showing, Opdivo’s chemo combo in this trial actually fell short of solo chemotherapy. Based on previous trial results, market watchers had been expecting the Opdivo chemo combo to succeed and the Opdivo-Yervoy pairing to fall short.

But for patients who can’t tolerate chemo or prefer to avoid it, the Opdivo-Yervoy combo offers an option, Peters said. “We used a low dose of ipilimumab (1mg every 6 weeks) to make it tolerable. Doing this led to a low rate of discontinuation and treatment-related toxicities or deaths. So it’s a highly manageable treatment.” 

The Checkmate-227 study enrolled patients who’d tested positive for the PD-L1 biomarker and those who didn’t. The PD-L1-positive patients were divided among three arms—Opdivo alone, Opdivo plus low-dose Yervoy, and chemotherapy alone. Those with PD-L1 levels of less than 1% were treated with either the Opdivo-Yervoy combo, Opdivo plus chemo, or chemo alone.

The trial began before any IO-chemo combos were approved and didn’t directly compare the Opdivo-Yervoy tandem to a chemo-combo option in PD-L1-positive patients.

Both Peters and a more skeptical cancer expert, Marina Chiara Garassino, M.D., of the Instituto Nazionale Dei Tumori in Milan, figure oncologists really need more data to know which type of treatment is really best for first-line patients. To Peters, the question of which combo to use won’t be answered until five-year survival data are available. Garassino said more biomarker information is needed to individualize therapy.

“We don’t yet know if the [Checkmate-227] findings are practice changing,” Garssino said adding that the trial didn’t directly compare Opdivo-Yervoy with Opdivo-plus-chemo in PD-L1-positive patients. “The comparison was chemotherapy alone, but this is no longer the standard for patients with metastatic NSCLC.”