5-year real-world outcomes with first-line pembrolizumab plus chemotherapy in advanced/metastatic NSCLC.

[BACKGROUND] First-line pembrolizumab plus chemotherapy has demonstrated durable, clinically meaningful survival benefits over 5 years, compared with chemotherapy alone, in pivotal clinical trials for patients with metastatic NSCLC. This retrospective study aimed to evaluate 5-year real-world outcomes with pembrolizumab plus chemotherapy at US oncology practices.

[METHODS] Using a nationwide, deidentified database, we selected adults with unresectable stage IIIB/IIIC/IV NSCLC and ECOG performance status of 0-1, excluding those in a clinical trial, who initiated first-line pembrolizumab plus platinum/pemetrexed from 1 June 2017 through 30 September 2021 (-wild-type nonsquamous NSCLC) or pembrolizumab plus carboplatin/(nab)-paclitaxel from 1 November 2018 through 30 September 2020 (squamous NSCLC). Overall survival (OS) from first-line initiation, by histology and PD-L1 expression, was estimated using the Kaplan-Meier method. Data cutoff was 30 September 2024.

[RESULTS] Median study follow-up was 60 months. Median (95% CI) OS was 15.0 months (13.4-16.0) and 12.9 months (10.3-17.1) among 1960 patients with nonsquamous and 433 with squamous NSCLC, respectively. At 5 years, OS rates were 21.6% and 18.2%, respectively, with 5-year OS rates by tumor PD-L1 < 1%/1-49%/≥50% expression of 15.8%/19.8%/32.6% in nonsquamous and 15.2%/14.1%/32.6% in squamous cohorts.

[CONCLUSIONS] First-line pembrolizumab plus chemotherapy demonstrates long-term effectiveness for nonsquamous and squamous advanced/metastatic NSCLC, with 5-year OS rates in real-world settings that are consistent across PD-L1 expression strata with 5-year outcomes from the pivotal clinical trials.