Glenwood Goss, MD, FRCPC, FCPSA, Professor of Medicine and Director of Clinical and Translational Research at the Ottawa Hospital Cancer Centre and University of Ottawa, Canada, formally discussed the findings. He noted that this combination in advanced melanoma showed “limited progression-free survival improvement that comes at the price of toxicity,” ie, a 55% rate of grade 3/4 adverse events.

Changing Scenario

When combined in the doses and schedules used in advanced melanoma, the nivolumab/ipilimumab combination was not well tolerated, he emphasized, adding, “You’ve got to admire these investigators for persisting in their quest.”

The modification of the dosing schedule has appeared, at least early on, to have changed this scenario. “The adverse events have come down substantially and are acceptable. Those leading to discontinuations are no greater than those seen with nivolumab alone and are less than seen in the original combination cohort,” Dr. Goss pointed out.

Note of Caution

The response rates of 13% to 39% “are quite acceptable and appear somewhat better than with monotherapy. It looks as though the combination is better than nivolumab alone in terms of response, with comparable toxicity,” he continued.

“But I caution,” he added. “The numbers are small, there is limited follow-up, and no meaningful progression-free or overall survival data. The response rate is at best 39%, there is a narrow therapeutic window between efficacy and toxicity, and the predictive relevance of PD-L1 [programmed cell death ligand 1] expression remains unanswered.” ■

Disclosure: Dr. Goss reported no potential conflicts of interest.