Expert Point of View: Paul Mitchell, MD

“The progression-free and overall survival curves of CheckMate 057 suggest the presence of two patient populations with respect to nivolumab (Opdivo): a relatively sensitive one and a less sensitive, possibly even resistant, one, according to invited discussant Paul Mitchell, MD, Associate Professor at the Olivia Newton-John Cancer and Wellness Centre in Melbourne, Australia.

“This is not unusual in immunotherapy trials…. It is very common to see this 30% or 40% or 50% of patients progressing within the first 2 to 4 months,” he maintained. “What is very important for us is to try and identify who these patients might be who are at risk of early death—there are some pointers from Dr. Peters’ presentation in terms of those with poor prognostic factors and programmed cell death ligand 1 low—especially as these drugs are being used in the community and in patients with a poor performance status and with comorbidities and being treated off trial.”

What is very important for us is to try and identify who these patients might be who are at risk of early death….
— Paul Mitchell, MD

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The 15 excess deaths with nivolumab in the first 3 months of treatment were “concerning,” but put in context, they made up just 5% of all patients randomized to that arm, and there was an excess of deaths in the docetaxel group in the second 3 months, Dr. Mitchell noted. “I don’t think our clinical practice should be colored by this. The overall benefit was very strong in the study for nivolumab.”

At the same time, the heightened risk of early mortality in some nivolumab-treated patients “highlights that we need more effective approaches to make more impact quicker in these groups of patients, with perhaps dual immunotherapies and perhaps chemoimmunotherapy combinations,” he concluded. ■

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