Abstract Rationale Pembrolizumab monotherapy is the preferred first-line treatment for advanced or metastatic non-small cell lung cancer (NSCLC) in patients whose tumors express PD-L1 on ≥ 50% of cells and lack actionable driver mutations, as it has been shown to significantly improve overall and progression-free survival. Although PD-1/PD-L1 inhibitors are known for their potential pulmonary toxicities and their association with pneumonitis is well established, data regarding their impact on acute respiratory distress syndrome (ARDS), pulmonary fibrosis, and pneumonia remain limited. Methods We conducted a retrospective cohort study using the TriNetX Research Network, a global database of de-identified electronic health records from multiple healthcare organizations. Adult patients (≥18 years) with a diagnosis of lung malignancy were identified using ICD-10 codes and categorized into two cohorts based on documented treatment with either pembrolizumab monotherapy or standard chemotherapy. The primary outcome was the incidence of lung toxicities, including ARDS, pulmonary fibrosis, and pneumonia. The secondary outcome assessed the severity of these toxicities and their associated 30-day all-cause mortality. Propensity score matching (1:1) was used to balance baseline characteristics, including age, sex, smoking status, obesity, history of radiotherapy, disease stage, and comorbidities. Statistical analyses were conducted within the TriNetX platform. Results After propensity score matching, a total of 20,920 patients were included, with 10,460 in each cohort. Pembrolizumab monotherapy was associated with a significantly lower risk of developing ARDS (RR 0.59, 95% CI 0.43-0.81, p 0.001) and showed no significant difference in 30-day all-cause mortality among those who developed ARDS compared with standard chemotherapy (RR 1.02, 95% CI 0.74-1.42, p = 0.893). It was also linked to a reduced risk of pulmonary fibrosis (RR 0.77, 95% CI 0.67-0.90, p = 0.009) with no significant difference in 30-day mortality (RR 0.85, 95% CI 0.60-1.20, p = 0.348), and bacterial pneumonia (RR 0.78, 95% CI 0.68-0.88, p 0.001) with a modest reduction in 30-day mortality (RR 0.83, 95% CI 0.69-0.99, p = 0.046). No significant differences were observed in the risk of viral pneumonia (RR 1.06, 95% CI 0.88-1.28, p = 0.540) or its 30-day mortality (RR 0.85, 95% CI 0.64-1.14, p = 0.273). However, pembrolizumab was associated with a higher risk of interstitial pneumonitis (RR 2.30, 95% CI 1.36-3.88, p = 0.001). Conclusions Pembrolizumab was associated with a lower risk of ARDS, pulmonary fibrosis, and bacterial pneumonia, with no significant difference in 30-day mortality when compared to standard chemotherapy. Suggesting that pembrolizumab has a favorable overall pulmonary safety profile despite its well-known association with interstitial pneumonitis. This abstract is funded by: None
Ortega et al. (Fri,) studied this question.
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