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. 2025 Oct;17(14):1005-1013.
doi: 10.1080/1750743X.2025.2569856. Epub 2025 Oct 17.

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

Stephen V Liu  1 , Riddhi A Babel  2 , Yu-Han Kao  3 , Diana Chirovsky  2 , Azadeh Namakydoust  4 , Vamsidhar Velcheti  5
Affiliations

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

Stephen V Liu et al. Immunotherapy. 2025 Oct.

Abstract

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 (EGFR/ALK-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.

Keywords: Advanced non-small cell lung cancer; immunotherapy; overall survival; platinum-based chemotherapy; real-world time on treatment; taxane; time to treatment discontinuation.

Plain language summary

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.

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Conflict of interest statement

Stephen V. Liu reports paid consultancy for Abbvie, Amgen, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo, Genentech/Roche, Gilead, GSK, Guardant Health, Johnson & Johnson, Jazz Pharmaceuticals, Lilly, Merck, Merus, Mirati, Natera, Novartis, OSE Immunotherapeutics, Pfizer, Regeneron, Revolution Medicines, Takeda, and Yuhan, and research grants (to his institution) from Abbvie, Alkermes, AstraZeneca, BioNTech, Bristol-Myers Squibb, Cogent Biosciences, Duality, Elevation Oncology, Ellipses, Genentech, Gilead, Medilink, Merck, Merus, Nuvalent, OSE Immunotherapeutics, Puma, RAPT, Synthekine, and SystImmune.

Riddhi A. Babel, Yu-Han Kao, Diana Chirovsky, and Azadeh Namakydoust are employees of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA, and hold stock of Merck & Co., Inc., Rahway, NJ, USA.

Vamsidhar Velcheti reports consultant/advisory roles for Bristol Myers Squibb, Merck, GSK Oncology, Amgen, Taiho Oncology, Takeda, Roche Diagnostics. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

References

    1. Howlader N, Forjaz G, Mooradian MJ, et al. The effect of advances in lung-cancer treatment on population mortality. N Engl J Med. 2020;383(7):640–649. doi: 10.1056/NEJMoa1916623 - DOI - PMC - PubMed
    1. Kratzer TB, Bandi P, Freedman ND, et al. Lung cancer statistics, 2023. Cancer. 2024;130(8):1330–1348. doi: 10.1002/cncr.35128 - DOI - PubMed
    1. Griesinger F, Ramagopalan S, Cheung WY, et al. Association between treatment and improvements in overall survival of patients with advanced/metastatic non-small cell lung cancer since 2011: a study in the United States, Canada, and Germany using retrospective real-world databases. Cancer. 2024;130(4):530–540. doi: 10.1002/cncr.35094 - DOI - PubMed

    2. • Large observational study of 51,318 patients in the US, Germany, and Canada with an incident advanced NSCLC diagnosis from 2011 to 2019, which found that OS, measured from the date of first-line initiation, improved over the observed time period in all three countries, a finding that the authors attributed to the introduction of new treatments.

    1. Siegel RL, Kratzer TB, Giaquinto AN, et al. Cancer statistics, 2025. CA Cancer J Clin. 2025;75(1):10–45. doi: 10.3322/caac.21871 - DOI - PMC - PubMed
    1. Gandhi L, Rodriguez-Abreu D, Gadgeel S, et al. Pembrolizumab plus chemotherapy in metastatic non-small-cell lung cancer. N Engl J Med. 2018;378(22):2078–2092. doi: 10.1056/NEJMoa1801005 - DOI - PubMed

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