DOI: 10.6084/m9.figshare.30383561.v1
title: 5-year real-world outcomes with first-line pembrolizumab plus chemotherapy in advanced/metastatic NSCLC

description: 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. 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 (<i>EGFR/ALK</i>-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. 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 &lt; 1%/1–49%/≥50% expression of 15.8%/19.8%/32.6% in nonsquamous and 15.2%/14.1%/32.6% in squamous cohorts. 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. The survival rate after a diagnosis of non-small cell lung cancer (NSCLC) in the United States (US) has been improving steadily over the past 20 years because of advances in testing and treatments, including immunotherapies that help patients’ own immune systems to fight cancer. Pembrolizumab is an immunotherapy that significantly improved long-term survival for patients in clinical trials over 5 years when used together with chemotherapy to treat metastatic NSCLC. However, patients in clinical trials are often younger and more carefully monitored than patients seen at real-world cancer clinics. Therefore, to understand the situation at real-world clinics, we used electronic medical record histories to study the survival of patients who had been treated with pembrolizumab plus chemotherapy for NSCLC that was too far advanced for surgical removal. We found that the survival of these patients was similar to that of patients treated in the clinical trials. At 5 years, 18% to 22% of patients (depending on the specific subtype of NSCLC) were still alive, comparable to the 18% to 19% survival rate reported in clinical trials at 5 years. These findings suggest that treatment with pembrolizumab plus chemotherapy shows long-term effectiveness for patients with advanced or metastatic NSCLC who are treated outside of clinical trials. In real-world US oncology settings, first-line therapy with pembrolizumab plus chemotherapy demonstrates long-term effectiveness for nonsquamous and squamous advanced/metastatic NSCLC, with 5-year outcomes consistent with those from KEYNOTE clinical trials