VIDEO: Checkpoint inhibitors show few efficacy, safety differences

This very important systematic review with data from a total of nearly 6,000 patients shows that severe toxicity is unusual with the PD-1 and PD-L1 inhibitors, and they result in no meaningful difference in response rates. The toxicities seen with these drugs are milder and less frequent than we see with standard chemotherapy drugs. The severe autoimmune toxicities seen are a major concern but are manageable and occurred at low rates.

In general, efficacy and toxicity does not appear to form a basis by which to choose among these drugs. Fatigue was the most common adverse event, which is surprising to see with these drugs although we are accustomed to seeing it in patients on standard chemotherapy. Fatigue can be a major issue for patients, even if it is relatively mild, because they remain on these drugs for periods as long as 2 years.

If the PD-1 and PD-L1 inhibitors continue to perform with similar efficacy and safety profiles, clinicians will be forced to turn to other parameters when trying to decide which drug specifically to prescribe. This can include issues of cost, reimbursement, and dosing convenience. Nivolumab, for example, has been administered more often, every 2 weeks, than the other drugs in these classes. Oncologists are trying to develop effective regimens with these drugs that can be given once every 3 or every 4 weeks. Future investigations may also look at the possibility of treating patients with these drugs initially for 6 months, and then scaling back to retreatment only when there is disease progression. If this approach is successful, it would obviate concerns about causing long-term fatigue or the inconvenience of more frequent treatment schedules.

We also need to continue to monitor and compare the toxicities of these immune checkpoint inhibitors as we move into using them in combination regimens.

Paul Mitchell, MD, is a medical oncologist at the Olivia Newton-John Cancer and Wellness Centre in Heidelberg, Australia. He has served on advisory boards for AstraZeneca, Boehringer Ingelheim, BMS, Celgene, Merck/MSD, Merck Serono, and Roche, and he has received honoraria from Merck and Roche, and he has received travel grants from BMS and Roche. He made these comments as the designated discussant for the report and in a video interview.