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363 KEYNOTE-042 5-year survival update: pembrolizumab versus chemotherapy in patients with previously untreated, PD-L1–positive, locally advanced or metastatic non–small-cell lung cancer
  1. Gilberto de Castro1,
  2. Iveta Kudaba2,
  3. Yi-Long Wu3,
  4. Gilberto Lopes4,
  5. Dariusz M Kowalski5,
  6. Hande Z Turna6,
  7. Christian Caglevic7,
  8. Li Zhang8,
  9. Boguslawa Karaszewska9,
  10. Konstantin K Laktionov10,
  11. Vichien Srimuninnimit11,
  12. Igor Bondarenko12,
  13. Kaoru Kubota13,
  14. Rinee Mukherjee14,
  15. Jianxin Lin14,
  16. Fabricio Souza14,
  17. Tony SK Mok15 and
  18. Byoung Chul Cho16
  1. 1Instituto do Câncer do Estado de São Paulo, São Paulo, Brazil
  2. 2Latvian Oncology Center, Riga East Clinical University, Riga, Latvia
  3. 3Guangdong Lung Cancer Institute, Guangdong Provincial People’s Hospital and Guangdong Academy of Medical Sciences, Guangdong, China
  4. 4Department of Medical Oncology, Sylvester Comprehensive Cancer Center at the University of Miami, Miami, FL, USA
  5. 5Department of Lung Cancer and Chest Tumours, Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw, Poland
  6. 6Department of Internal Medicine, Istanbul University Cerrahpasa Medical Faculty, Istanbul, Turkey
  7. 7Cancer Research Department, Instituto Oncologico Fundacion Arturo Lopez Perez, Santiago, Chile
  8. 8Peking Union Medical College Hospital, Beijing, China
  9. 9Przychodnia Lekarska KOMED, Konin, Poland
  10. 10Federal State Budgetary Institution “N.N. Blokhin National Medical Research Center of Oncology” of the Ministry of Health of the Russian Federation (N.N Blokhin NMRCO), Moscow, Russian Federation
  11. 11Department of Medicine, Siriraj Hospital, Bangkok, Thailand
  12. 12Oncology and Medical Radiology Department, Dnipro State Medical University, Dnipro, Ukraine
  13. 13Department of Pulmonary Medicine and Oncology, Nippon Medical School Hospital, Tokyo, Japan
  14. 14Merck and Co., Inc., Kenilworth, NJ, USA
  15. 15Clinical Oncology, State Key Laboratory of Translational Oncology, Chinese University of Hong Kong, Shatin, Hong Kong, China
  16. 16Division of Medical Oncology, Yonsei Cancer Center, Seoul, Korea, Republic of


Background Primary analysis of KEYNOTE-042 (NCT02220894), a global, randomized, phase 3 trial, showed that pembrolizumab significantly improved OS versus platinum-based chemotherapy in patients with locally advanced or metastatic non–small-cell lung cancer (NSCLC) without sensitizing EGFR/ALK alterations and with PD-L1 tumor proportion score (TPS) ≥50%, ≥20%, and ≥1% with fewer treatment-related AEs than chemotherapy. We report an updated analysis with ~5 years of follow-up.

Methods Eligible adults were randomized 1:1 to receive pembrolizumab 200 mg Q3W for 35 cycles or investigator’s choice of chemotherapy (carboplatin + paclitaxel or pemetrexed) Q3W for 4–6 cycles with optional maintenance pemetrexed (nonsquamous only). Primary endpoints were OS in patients with PD-L1 TPS ≥50%, ≥20%, and ≥1%; secondary endpoints included PFS and ORR per RECIST v1.1 by central review, and safety (secondary). Eligible patients randomized to pembrolizumab who completed 35 cycles with SD or better or stopped treatment after confirmed CR could begin a second course of pembrolizumab at the time of progression.

Results 1274 patients were randomized to pembrolizumab or chemotherapy (n = 637 each). Median (range) time from randomization to data cutoff (Apr 28, 2021) was 61.1 (50.0–76.3) months. OS outcomes favored the pembrolizumab group (vs chemotherapy alone) regardless of PD-L1 TPS (HR [95% CI] for TPS ≥50%, 0.68 [0.57–0.81]; TPS ≥20%, 0.75 [0.64–0.87]; TPS ≥1%, 0.79 [0.70–0.89]), with estimated 5-year OS rates (95% CI) of 21.9% (17.3%–26.9%), 19.4% (15.6%–23.4%) and 16.6% (13.7%–19.6%), respectively, in the pembrolizumab group (table 1). Median duration of response (DOR) was 28.1 vs 10.8 months in PD-L1 TPS ≥50% group, 27.7 vs 10.8 months in PD-L1 TPS ≥20% group and, 26.5 vs 8.4 months in PD-L1 TPS ≥1% for pembrolizumab group vs chemotherapy. Treatment-related grade 3–5 AEs occurred in 120 patients (18.9%) in the pembrolizumab group and 257 (41.8%) in the chemotherapy group. Among 102 patients who completed 35 cycles of pembrolizumab: ORR was 84.3%; estimated 4-year OS rate after completion of 35 cycles of pembrolizumab (ie, approximately 6 years after randomization) was 61.8%. Among 33 patients who received second-course pembrolizumab, ORR was 15.2%.

Abstract 363 Table 1

Key efficacy outcomes in the KEYNOTE-042 ITT population

Conclusions With 5 years of follow-up, first-line pembrolizumab monotherapy continued to show substantial clinical benefit with higher 5-year OS rates, and durable response over chemotherapy in patients with PD-L1–positive, locally advanced/metastatic NSCLC without EGFR/ALK alterations. First-line pembrolizumab remains a standard of care in patients with PD-L1 TPS ≥1%, as underscored by these long-term results.

Acknowledgements Medical writing assistance was provided by Kathleen Estes, PhD, of ICON plc (North Wales, PA, USA). This assistance was funded by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.

Clinicaltrials gov, NCT02220894

Ethics Approval The protocol and all amendments were approved by the appropriate ethics committee at each center, the study was conducted in accordance with the standards of Good Clinical Practice and in compliance with the Declaration of Helsinki. Patients provided written informed consent before enrollment.

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