Background Data from prospective phase 3 trials of anti-PD-1 and anti-CTLA-4 demonstrate durable clinical benefit even in patients who discontinue ICI due to treatment related adverse events. However, outcomes for patients treated with anti-PD-1 therapy alone or with chemotherapy who discontinue treatment due to immune toxicities is unknown.
Methods We retrospectively evaluated patients with stage IV NSCLC treated with first line ICI alone or with platinum-based chemotherapy at a tertiary cancer center between 2017 and 2021. Overall survival (OS) was calculated from the date of ICI treatment initiation to death from any cause or date of last follow-up. Patients still alive were censored at last follow-up. Overall survival was estimated using Kaplan-Meier method.
Results 225 patients were identified and included, mean age 63.5 years, 57% were male, 91% former/current smokers, 17% squamous histology. ICI type was anti-PD-1 alone in 43%, ICI+chemotherapy in 56%, and ICI+ICI in 1%. 42 out of 225 patients had treatment held either temporarily or permanently for irAE (42/225, 19%, table 1). Of these patients, 19 were permanently discontinued from irAE and 22 were resumed on ICI (1 missing due to lost follow up). There was no difference in patient age, race, sex, smoking status, histology, or ICI type among patients with irAE and permanent ICI discontinuation vs not (table 2), however permanent discontinuation was more common in treatment with ICI monotherapy (60% vs 37% in ICI+Chemo vs 0% in ICI+ICI), but not statistically significant (p=0.13). Among all patients with any irAE treatment interruption, the median overall survival (mOS) was 54.1 months (95% CI 26.9, NR). There was no significant difference in mOS among patients who permanently discontinued ICI: 26.9 months (95% CI 3.3, NR) vs 22.8 months (95% CI 16.3, 28.1) for all other patients, p=0.84 (figure 1). Among patients with treatment interruption for irAE, there was no significant difference in mOS among those who resumed treatment vs those who permanently discontinued, though this may have been limited by sample size: 54.1 months (95% CI 26.9, NR) vs 26.9 months (95% CI 3.3, NR) (p=0.07, figure 2).
Conclusions We observed no significant difference in mOS between patients with treatment interruption or discontinuation due to irAE. There appeared to be longer OS in patients who resumed treatment, though this was nonsignificant and likely limited by small sample size. These findings are consistent with continued clinical benefits despite treatment discontinuation in patients treated with first line ICI alone or with chemotherapy.
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