ESMO I-O: BMS zooms in on squamous lung cancer patients as it dissects Opdivo-chemo combo failure

opdivo
Nearly 60% of previously untreated patients with squamous non-small cell lung cancer responded to Bristol's Opdivo-chemo pairing in Part 2 of the Checkmate-227 trial, BMS said Thursday. (Bristol-Myers Squibb)

GENEVA—As Bristol-Myers Squibb continues to search for bright spots in its eyebrow-raising Opdivo-chemo combo fail from June, it’s zeroing in on the population of squamous lung cancer patients who seemed to benefit.

Nearly 60% of previously untreated patients with squamous non-small cell lung cancer responded to treatment with the Opdivo-chemo pairing in Part 2 of BMS’ Checkmate-227 trial, and the duo cut the risk of disease progression or death in that population by 49%, presenters said Thursday at the ESMO Immuno-Oncology Congress. That’s well ahead of the 38% and 33% risk reductions that all-comers and non-squamous patients saw.

RELATED: Can BMS parlay its surprise 'win and a miss' in first-line lung cancer into a net gain?

The numbers are part of an exploratory analysis, presenters stressed, and they follow up on the 31% reduction in squamous patients’ risk of death that BMS unveiled over the summer. The company delivered that finding alongside news that Checkmate-227 Part 2 had missed its primary endpoint, with Opdivo-chemo failing to significantly outdo chemo at extending non-squamous patients’ lives.

The analysis could inform the design of future studies, session chair Alessandra Curioni said in a discussion following the presentation. But patients’ histology—that is, squamous or non-squamous—shouldn’t be the only thing taken into consideration, and neither should biomarkers, she added.

“Sometimes we need to look as well at our patients, at the clinical features,” she said—particularly where biomarkers can’t paint an informative picture, such as in Part 2 of the Checkmate-227 trial.

Factors such as whether patients have smoked and whether they have liver metastases may affect their responses to chemo, she noted. And in fact, some of those factors may help explain why Bristol’s chemo-combo failed to significantly outdo chemo the way rival regimens from Merck & Co. and Roche did in those companies’ own trials.

For instance, Bristol’s patient pool had a higher percentage of “never-smokers” receiving chemo, at 24%, than the chemo groups in Merck’s and Roche’s trials, which came to about 10% and 20%, respectively, Curioni said.

“It’s difficult, it’s very difficult—and I would bring this from the point of the clinician who has to make a choice” between therapies—“to compare all the studies that are using … different antibodies and different subgroups of patients,” she said.

For now, though, thanks to the trial miss, doctors won’t have a chemo-combo from Bristol as one of their options for newly diagnosed patients; they’re currently choosing between Merck’s Keytruda-chemo combo and a chemo combo featuring Roche’s Tecentriq, with or without fellow Roche drug Avastin. Keytruda is also available for use as a solo therapy, while Tecentriq seems poised for a monotherapy OK of its own.

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

Bristol is looking to get in on the action, though—and it may soon be able to, thanks to a surprise win from Part 1 of the same Checkmate-227 trial. That portion showed the PD-1 therapy, in tandem with CTLA4 product Yervoy, could extend the lives of patients with levels of biomarker PD-L1 that measured greater than 1%.

Thanks to the chemo-combo success from fellow PD-1 drugmaker Merck and a major flop from AstraZeneca’s PD-L1/CTLA4 duo, some industry watchers had expected the reverse outcome: that Part 1 of Bristol’s trial would come up short and Part 2 would hit its marks.

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