Expert Point of View: Paul Mitchell, MD

“The KEYNOTE-010 updated survival is looking even more impressive with the benefit of pembrolizumab (Keytruda) over docetaxel. Survival at 2 years with pembrolizumab is more than double that with chemotherapy,” commented invited discussant, Paul Mitchell, MD, Associate Professor at the Olivia Newton-John Cancer and Wellness Centre in Melbourne, Australia.

“Responding patients do not relapse early on planned cessation of pembrolizumab, although to date, the patient numbers are small, and the follow-up is short,” he cautioned.

A Few Questions

This trial and others still need to address a few questions about immune checkpoint inhibitor therapy going forward, according to Dr. Mitchell.

What we really need to know is whether a brief course of PD-1 or PD-L1 inhibition is sufficient.
— Paul Mitchell, MD

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The first question is how much therapy is enough? “Most of these studies have either treated to disease progression or, in the case of pembrolizumab studies, to 2 years. What we really need to know is whether a brief course of a programmed cell death protein 1 (PD-1) or programmed cell death ligand 1 (PD-L1) inhibition is sufficient?” he elaborated. “That may avoid patient inconvenience, potentially avoid excess toxicity in patients, and would save considerable expense. This would require at least one major randomized trial to ask this question.”

A second key question is whether retreatment with these agents is effective in patients with lung cancer who have had a response in the past. In the melanoma population, for example, research has established that retreatment with the immune checkpoint inhibitor ipilimumab (Yervoy) achieves a response rate of 23% and a disease control rate of 48%.1

“We need to focus on this question in terms of how best we can use these agents,” Dr. Mitchell proposed. “There are patients who go off of treatment for various reasons, and it might be for toxicity or it might be for financial reasons. It is important that we know what the possibility of a re-response is if they have an interval from treatment.” ■

Disclosure: Paul Mitchell, MD, is on the advisory boards of Bristol-Myers Squibb, Merck (MSD), AstraZeneca, Roche, and Celgene; has received travel grants from Bristol-Myers Squibb and Roche; and honoraria from Roche.


1. Lebbé C, Weber JS, Maio M, et al: Survival follow-up and ipilimumab retreatment of patients with advanced melanoma who received ipilimumab in prior phase II studies. Ann Oncol 25:2277-2284, 2014.

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