Baseline characteristics of those 68 patients were fairly similar, although patients in the re-treatment cohort were more likely to be treated in the first-line setting (66% vs 30%; P = .007).
The most common initial irAEs that led to treatment interruption or discontinuation included pneumonitis (19%), colitis (17%), rash (16%), and liver enzyme abnormalities (10%). There were no differences in the types of events or in the timing of the first irAE between the re-treatment and discontinuation groups (a median onset of 69 and 73 days, respectively).
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Initial irAEs were less severe in the re-treatment group and required fewer hospitalizations, a shorter course of steroids, and no instances of tumor necrosis factor-alpha inhibitor use compared with the discontinuation cohort.
The majority of the recurrent or new irAEs were mild (58% were grade 1 or grade 2), and manageable, with 84% resolving or improving to grade 1. There were two treatment-related deaths, however.
“It’s very frustrating when an AE does happen when we’re using immunotherapy,” Dr Wrangle said. “It can be devastating. When the patient develops a grade 3 or grade 4 AE, that’s transitioning [a response] from [simply] affecting quality of life to [an effect that is] life-threatening.”
Study authors reported recurrent and new irAEs were more likely if the initial irAE had required hospitalization, with a higher frequency of recurrent/new irAEs in patients who initially experienced arthralgia or myalgia.
Drug selection in the second-line setting may have influenced the decision to discontinue treatment; Dr Wrangle noted that the patients across the discontinuation group received different drugs as second-line therapies.
Although re-treatment with a checkpoint inhibitor is now generally discouraged and counter to treatment guidelines, according to Dr Wrangle, his team’s analysis reflects a period in which “no data previously existed [to aid] in this decision.”1
The study authors wrote that even though they determined re-treatment could be a viable option for some patients — it is not an approach that necessarily should be used in routine practice.
“The efficacy analysis of patients who had an objective response prior to the onset of an irAE were similar in the re-treatment cohort and discontinuation cohorts,” wrote the authors. “We conclude that for patients who achieved an objective response and developed an irAE that requires holding immunotherapy, re-treatment upon improvement/recovery of the irAE should not be encouraged.”
References
- Santini FC, Rizvi H, Plodkowski AJ, et al. Safety and efficacy of re-treating with immunotherapy after immune-related adverse events in patients with NSCLC [published online July 10, 2018]. Cancer Immunol Res. doi: 10.1158/2326-6066.CIR-17-0755
- Santini FC, Rizvi H, Wilkins O, et al. Safety of retreatment with immunotherapy after immune-related toxicity in patients with lung cancers treated with anti-PD(L)-1 therapy. Abstract presented at: the American Society of Clinical Oncology Annual Meeting; June 2017; Chicago, IL. doi: 10.1200/JCO.2017.35.15_suppl.9012
