Sanjay Popat, FRCP, PhD

Formal discussant of the CheckMate 227 trial, Sanjay Popat, FRCP, PhD, of the Royal Marsden Hospital, London, had some reservations about endorsing nivolumab/ipilimumab as a new standard of care, mainly related to toxicity. “The landscape of treating advanced non–small cell lung cancer has changed dramatically, with many twists and turns,” he said. “We have many options in therapy, but I question whether nivolumab/ipilimumab is the preferred regimen in clinical practice.”

Dr. Popat noted that CheckMate 227 was intended to answer many questions. “Nivolumab/ipilimumab improves survival, and this is driven by the programmed cell death ligand 1–high expressor group. If we use nivolumab/ipilimumab, the combination may not be worth the benefit, because one-third of patients have grade 3 and 4 treatment-emergent adverse events,” he continued. “With limited efficacy, nivolumab monotherapy has no role in the front-line setting. Ipilimumab adds efficacy to nivolumab monotherapy, but at the meaningful cost of toxicities. Tissue tumor mutational burden testing is not discriminatory to predict a survival benefit.”

‘Let the Buyer Beware’

According to Dr. Popat, when it comes to the use of nivolumab/ipilimumab in this patient population, “caveat emptor—let the buyer beware. The hazard ratio for survival with nivolumab/ipilimumab is not better than that for all other monotherapies. There is a similar survival benefit with other single-agent checkpoint inhibitors and less toxicity. Finally, if ipilimumab really does add something, it is not clear that nivolumab is the best checkpoint inhibitor to combine it with.” ■

DISCLOSURE: Dr. Popat reported financial relationships with Boehringer Ingelheim, AstraZeneca, Pfizer, Roche, Takeda, Bristol-Myers Squibb, Novartis, Merck Serono, Guardant Health, AbbVie, Merck Sharp & Dohme, and Lilly.