More patients with non-small cell lung cancer (NSCLC) are being treated with anti-programmed cell death ligand 1 (PD-L1) checkpoint inhibitors, but immune-related adverse events (irAEs) can occur and can lead to treatment discontinuation. Once this type of AE occurs, the safety and benefit of re-treatment is not as clear-cut.
“These events are infrequent,” said Fernando Santini, MD, of the Thoracic Oncology Service at Memorial Sloan Kettering Cancer Center in New York, New York. The center’s large retrospective analysis suggested select patients may benefit from re-treatment, and that in these patients, re-treatment is both safe and feasible.1
“[These are] good retrospective data giving guidance about how to navigate a very tricky issue,” said John Wrangle, MD, an immunologist at the Hollings Cancer Center at the Medical University of South Carolina in Charleston, who was not involved in the study. “As a treating oncologist, there is a fear we experience when we [re-treat patients with an] agent [that caused] a severe side effect, but there’s a compelling rationale [for] why you [would] want to do it, especially in patients who have responded to the therapy in question.”
Dr Wrangle said this study is “not definitive by any means,” but it does help oncologists make “a tough decision while better data [are] being accumulated.”
When Dr Santini presented initial data at the 2017 American Society of Clinical Oncology Annual Meeting, he said, “there is no standard protocol for how long to treat a patient with NSCLC using checkpoint inhibitors,” and that treatment is typically discontinued when there is a grade 3 or grade 4 toxicity.2 The current study is the first to retrospectively analyze data on more than just a few case reports.1
This retrospective study evaluated patients with advanced NSCLC who were treated with anti-PD-1 and anti-PD-L1 therapy either as a monotherapy or in combination with either anticytotoxic T-lymphoctye–associated antigen (CTLA)-4 at Memorial Sloan Kettering Cancer Center from April 2011 to May 2016.1 Of 482 patients with NSCLC treated with a PD-L1 or PD-1 inhibitor, 68 (14%) developed a serious irAE requiring treatment interruption. Of these patients, 38 (56%) were re-treated once the reaction resolved and 30 (44%) discontinued treatment. In the re-treatment cohort, 18 (48%) patients had no subsequent irAEs, 10 patients (26%) had recurrence of the initial irAE, and 10 patients had a new irAE.
“This was a 500-patient study, but the true study population of interest is 68 patients. That suggests that to have something definitive, thousands of treated patients would have to be observed to generate a population that could then be randomized to re-treatment or discontinuation [cohorts] stratified by irAE severity, and that is unlikely to ever happen,” Dr Wrangle said.