Author(s): James Chih-Hsin Yang, MD, PhD1; Dae Ho Lee, MD, PhD2; Jong-Seok Lee, MD, PhD3; Yun Fan, MD4; Filippo de Marinis, MD, PhD5; Eiji Iwama, MD, PhD6; Takako Inoue, MD7; Jerónimo Rodríguez-Cid, MD8; Li Zhang, MD9; Cheng-Ta Yang, MD10; Emmanuel de la Mora Jimenez, MD11; Jianying Zhou, MD12; Maurice Pérol, MD13; Ki Hyeong Lee, MD, PhD14; David Vicente, MD15; Eiki Ichihara, MD, PhD16; Gregory J. Riely, MD, PhD17; Yiwen Luo, PhD18; Diana Chirovsky, PhD18; M. Catherine Pietanza, MD18; Niyati Bhagwati, MD18; Shun Lu, MD, PhD19
PURPOSE
Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are standard first-line therapy for EGFR-mutant, metastatic non–small cell lung cancer (NSCLC); however, most patients experience disease progression. We report results from the randomized, double-blind, phase III KEYNOTE-789 study of pemetrexed and platinum–based chemotherapy with or without pembrolizumab for TKI-resistant, EGFR-mutant, metastatic nonsquamous NSCLC (ClinicalTrials.gov identifier: NCT03515837).
METHODS
Adults with pathologically confirmed stage IV nonsquamous NSCLC, documented DEL19 or L858R EGFR mutation, and progression after EGFR-TKI treatment were randomly assigned 1:1 to 35 cycles of pembrolizumab 200 mg or placebo once every 3 weeks plus four cycles of pemetrexed and carboplatin or cisplatin once every 3 weeks and then maintenance pemetrexed. Dual primary end points were progression-free survival (PFS) and overall survival (OS). Final PFS testing was completed at the second interim analysis (IA2; data cutoff, December 3, 2021); OS was tested at final analysis (FA; data cutoff, January 17, 2023). Efficacy boundaries were one-sided P = .0117 for PFS and OS.
RESULTS
Four hundred ninety-two patients were randomly assigned to pembrolizumab plus chemotherapy (n = 245) or placebo plus chemotherapy (n = 247). At IA2, the median PFS was 5.6 months for pembrolizumab plus chemotherapy versus 5.5 months for placebo plus chemotherapy (hazard ratio [HR], 0.80 [95% CI, 0.65 to 0.97]; P = .0122). At FA, the median OS was 15.9 versus 14.7 months, respectively (HR, 0.84 [95% CI, 0.69 to 1.02]; P = .0362). Grade ≥3 treatment-related adverse events occurred in 43.7% of pembrolizumab plus chemotherapy recipients versus 38.6% of placebo plus chemotherapy recipients.
CONCLUSION
Addition of pembrolizumab to chemotherapy in patients with TKI-resistant, EGFR-mutant, metastatic nonsquamous NSCLC did not significantly prolong PFS or OS versus placebo plus chemotherapy in KEYNOTE-789.
Author Affiliations
1National Taiwan University Hospital and National Taiwan University Cancer Center, Taipei, Taiwan;
2Department of Oncology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, South Korea;
3Seoul National University Bundang Hospital, Seoul, South Korea;
4Zhejiang Cancer Hospital, Hangzhou, China;
5Istituto Europeo di Oncologia, IRCCS, Milan, Italy;
6Department of Respiratory Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan;
7Osaka International Cancer Institute, Osaka, Japan;
8Oncology Center, Medica Sur Hospital, Mexico City, Mexico;
9Peking Union Medical College Hospital, Beijing, China;
10Chang Gung Memorial Hospital, Taoyuan, Taiwan;
11Instituto Jalisciense de Cancerología, Guadalajara, Mexico;
12The First Affiliated Hospital, Zhejiang University, Zhejiang, China;
13Centre Léon Bérard, Lyon, France;
14Chungbuk National University Hospital, Cheongju-si, South Korea;
15Hospital Universitario Virgen Macarena, Sevilla, Spain;
16Okayama University Hospital, Okayama, Japan;
17Memorial Sloan Kettering Cancer Center, New York, NY;
18Merck & Co, Inc, Rahway, NJ;
19Shanghai Chest Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, China;
