Objective To describe the effectiveness and safety of pembrolizumab in routine clinical practice as first-line treatment for advanced/metastatic non-small cell lung cancer (NSCLC) with PD-L1 expression ≥ 50% and without EGFR or ALK alterations. Methods Retrospective, multicenter observational study including patients diagnosed with advanced/metastatic NSCLC treated with pembrolizumab monotherapy as first-line therapy between January 2016 and July 2020. Clinical, treatment-related, and safety variables were collected. The primary effectiveness endpoints were overall survival (OS) and progression-free survival (PFS), estimated using the Kaplan–Meier method. Results A total of 1005 patients from 42 Spanish hospitals were included, with a median age of 67 years (interquartile range IQR: 14); 256 were women. The predominant histology was non-squamous (725 patients). Median follow-up was 17.9 months (IQR: 24.1), and the median number of treatment cycles received was 8 (IQR: 21). Median PFS and OS were 8.7 months (95% confidence interval CI: 7.2–10.1) and 18.0 months (95% CI: 16.2–21.3), respectively. In the bivariate analysis, factors significantly associated with shorter OS included: age ≥ 75 years, body mass index (BMI) < 25 kg/m 2 , never smoking, performance status (PS-ECOG) ≥ 2, squamous histology, baseline liver or brain metastases, ≥ 2 metastatic sites at diagnosis, Lung Immune Prognostic Index (LIPI) 1–2, and prior exposure to proton pump inhibitors (PPIs), corticosteroids, and antibiotics (within the previous 10 days). Overall, 61.7% of patients experienced some degree of toxicity (G1–5), and 15.3% had G ≥ 3 toxicities. Treatment discontinuation due to toxicity occurred in 115 patients (12.7%). Patients who developed toxicity had a median OS of 28.3 months (95% CI: 23.9–34.5), compared to 6.5 months (95% CI: 5.1–9.2) in those without toxicity ( p < 0.0001). Conclusions In advanced/metastatic NSCLC with PD-L1 ≥ 50% and no EGFR/ALK alterations, first-line pembrolizumab demonstrates outcomes consistent with the pivotal trial and with published real-world evidence. The findings confirm that PS-ECOG ≥ 2 and prior PPI exposure are predictors of shorter OS, and that the development of toxicity during treatment is significantly associated with longer survival.
Burgos et al. (Mon,) studied this question.