P78.05 Patterns of irAE During First Line Pembrolizumab for NSCLC: Incidence, Risk Factors, and Impact on Clinical Outcome

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Conference Proceeding

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Journal of Thoracic Oncology


Introduction: Pembrolizumab monotherapy is the preferred treatment option for patients with stage IV non-small cell lung cancer (NSCLC) with programmed death-ligand 1 (PD-L1) tumor expression ≥ 50% and no actionable driver mutations. There is little real word data on immune-related adverse events (irAEs) with first-line pembrolizumab. In this study, we aim to better understand irAE incidence, risk factors, and impact on clinical outcome in treatment naïve patients receiving first-line pembrolizumab therapy.

Methods: We conducted a multicenter, retrospective study of patients with treatment-naïve NSCLC and a PD-L1 expression of ≥50% treated with first line pembrolizumab monotherapy between June 2016 and January 2020. irAEs were determined by treating physician diagnosis and lack of alternative etiologies. Risk factors for irAE occurrence were determined using a logistic regression model. Overall survival (OS) was measured from the date of therapy initiation to death or the last point of follow-up. Survival was estimated by the Kaplan-Meier method. Cox proportional hazards were used to determine the association between irAE and OS while treating irAE as a time-dependent variable. P < 0.05 was considered significant.

Results: In our cohort of 153 patients, the median age was 66 years old (range 41-90); 37% of patients were female, 76.4% of patients had adenocarcinoma, and 21.5% had squamous cell carcinoma. Median follow-up time was 12 months. irAEs occurred in 65 patients (42.4%) with 23 (15.1%) developing irAE CTCAE grade ≥ 3. The most common high grade irAEs were pneumonitis (n=9), colitis (n=6), and hepatitis (n=2). Higher risk for irAE was associated with current tobacco use or cessation of tobacco use(odds ratio [OR] 2.27, 95% confidence interval [CI] 1.14-4.52, P=0.02), prior or concurrent radiation therapy (OR 2.03, 95 %CI 1.06-3.90, P=0.03), neutrophil-lymphocyte ratio (NLR) >5 prior to starting therapy (OR 2.33, 95% CI 1.19-4.56, P=0.01), and longer course of pembrolizumab treatment (OR 1.039 per cycle, 95% CI 1.009-1.070, p=0.011). There was no difference in OS between patients who experienced low grade irAEs (

Conclusion: Risk factors for the development of irAEs during first-line pembrolizumab included current or recent smoking status, NLR >5 prior to treatment start, prior or concurrent radiation therapy, and longer exposure to therapy. Higher grade irAEs and those events leading to discontinuation were associated with worse OS, and no OS benefit was observed in patients with lower grade adverse events. Our study identifies patients at high risk for irAEs who may benefit from closer monitoring during therapy. The lack of survival benefit from irAE in NSCLC patients with high PD-L1 expression has not previously been reported and warrants further investigation.





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