6ER-045 Effectiveness and safety of first-line chemoimmunotherapy with pembrolizumab for metastatic non-squamous non-small-cell lung cancer

<h3>Background and Importance</h3> Lung carcinoma is the leading cause of cancer-related death in the world. Pembrolizumab is a human IgG4 monoclonal antibody that binds to the PD-1, enhancing the immune response of T-cells. <h3>Aim and Objectives</h3> To evaluate effectiveness and safety of chemoimmunotherapy with pembrolizumab for metastatic non-squamous non-small-cell lung cancer (NSQ-NSCLC), without driver mutations EGFR/ALK. Secondary endpoint was to evaluate the impact of different variables on overall survival (OS). <h3>Material and Methods</h3> Retrospective observational study including all patients with metastatic NSQ-NSCLC who received platinum-based chemotherapy and pembrolizumab from January 2018 to July 2024. Data collected: histology, smoking, ECOG, metastasis, PD-L1 expression, chemotherapy, frequency and severity of adverse events (AEs), and treatment discontinuation due to AEs. Effectiveness was evaluated by median OS, progression-free survival (PFS), objective response rate (ORR) and disease control rate (DCR), calculated with Kaplan-Meier estimator, STATA v.16.0. Multivariate analysis was performed by Cox regression, expressed as hazard ratio (HR). <h3>Results</h3> Eighty-eight patients (69% men) with a median age of 65 years (RIC:56–70) were included. Histology: adenocarcinoma (89%), undifferentiated (8%), large cell carcinoma (2%) and mixed (1%). The 91% were ex-/smokers, with a median Pack-Year-Index of 40 (RIC:25–50); and 65% had ECOG 0–1. The 53% presented bone, 29% brain and 18% liver metastasis. The 50% had PD-L1&lt;1%, negative or not-performed, 33% 1–49% and 17% PD-L1≥50%. The 91% received carboplatin vs 9% cisplatin. ORR was 56% (9% complete response) and DCR was 69%. Median OS and PFS were 10.6 months 95% CI (7.7–13.8) and 5 months 95% CI (4.3–7.7), respectively. One-year and 5 year OS rate were 46% and 13%, and 1 year and 5 year PFS were 21% and 12%, respectively. Ninety-nine percent experienced AEs: asthenia (57%), anaemia (28%), neutropenia (26%) and infection (24%). 47% suffered grade 3–4 AEs, mainly asthenia (22%). 17% discontinued treatment due to AEs. Regarding multivariate analysis, statistically significant variables were: ex-/smoker 5.0 (95% CI: 1.5–17); p=0.01; bone metastasis 2.6 (95% CI: 1.4–4.9); p=0.004; brain metastasis 1.9 (95% CI: 1.06–3.6); p=0.033 and ECOG 0–1 0.39 (95% CI: 0.21–0.72); p=0.003. <h3>Conclusion and Relevance</h3> More than half of the patients responded to treatment, however only a small part were alive or free from disease 5 years later. Smoking, bone and brain metastasis were associated with less survival. Most patients experienced AEs that caused discontinuation of therapy, which emphasises the need to adequately select patients. <h3>References and/or Acknowledgements</h3> <h3>Conflict of Interest</h3> No conflict of interest