Nivolumab Plus Chemotherapy in Epidermal Growth Factor Receptor–Mutated Metastatic Non–Small-Cell Lung Cancer After Disease Progression on Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors: Final Results of CheckMate 722

Author(s): Tony Mok, MD, FRCPC, FASCO1; Kazuhiko Nakagawa, MD, PhD2; Keunchil Park, MD, PhD3,4; Yuichiro Ohe, MD, PhD5; Nicolas Girard, MD6; Hye Ryun Kim, MD, PhD7; Yi-Long Wu, MD8; Justin Gainor, MD9; Se-Hoon Lee, MD, PhD3; Chao-Hua Chiu, MD10,11; Sang-We Kim, MD, PhD12; Cheng-Ta Yang, MD13; Chien Liang Wu, MD14; Lin Wu, MD15; Meng-Chih Lin, MD16; Jens Samol, MD17,18; Kazuya Ichikado, MD19; Mengzhao Wang, MD20; Xiaoqing Zhang, MD, PhD21; Judi Sylvester, BS21; Sunney Li, PhD21; Ann Forslund, PhD21; James Chih-Hsin Yang, MD, PhD22
Source: https://doi.org/10.1200/JCO.23.01017
Maem Hussein MD

Dr. Maen Hussein's Thoughts

This is the same issue as the Phase III, Randomized Study of Atezolizumab Plus Bevacizumab and Chemotherapy in Patients With EGFR- or ALK-Mutated Non–Small-Cell Lung Cancer (ATTLAS, KCSG-LU19-04) article, this one was negative though. A question for the previous trial would be: do we need PDL-1 inhibitor, or just VEGF inhibitor, recall the pts with tumors with high PDL-1 expression did better though, so most likely we need both with chemotherapy.

PURPOSE

The phase III CheckMate 722 trial (ClinicalTrials.gov identifier: NCT02864251) evaluated nivolumab plus chemotherapy versus chemotherapy in patients with epidermal growth factor receptor (EGFR)–mutated metastatic non–small-cell lung cancer (NSCLC) after disease progression on EGFR tyrosine kinase inhibitors (TKIs).

METHODS

Patients with disease progression after first- or second-generation EGFR TKI therapy (without EGFR T790M mutation) or osimertinib (with/without T790M mutation) were randomly assigned 1:1 to nivolumab (360 mg once every 3 weeks) plus platinum-doublet chemotherapy (once every 3 weeks) or platinum-doublet chemotherapy alone (once every 3 weeks) for four cycles. Primary end point was progression-free survival (PFS). Secondary end points included 9- and 12-month PFS rates, overall survival (OS), objective response rate (ORR), and duration of response (DOR).

RESULTS

Overall, 294 patients were randomly assigned. At final analysis (median follow-up, 38.1 months), PFS was not significantly improved with nivolumab plus chemotherapy versus chemotherapy (median, 5.6 v 5.4 months; hazard ratio [HR], 0.75 [95% CI, 0.56 to 1.00]; P = .0528), with 9- and 12-month PFS rates of 25.9% versus 19.8%, and 21.2% versus 15.9%, respectively. Post hoc PFS subgroup analyses showed a trend favoring nivolumab plus chemotherapy in patients with tumors harboring sensitizing EGFR mutations (HR, 0.72 [95% CI, 0.54 to 0.97]), one line of previous EGFR TKI (0.72 [95% CI, 0.54 to 0.97]), or both (0.64 [95% CI, 0.47 to 0.88]). Median OS was 19.4 months with nivolumab plus chemotherapy versus 15.9 months with chemotherapy, while ORR was 31.3% versus 26.7%, and median DOR was 6.7 versus 5.6 months, respectively. Grade 3/4 treatment-related adverse events occurred in 44.7% and 29.4% of patients treated with nivolumab plus chemotherapy and chemotherapy alone, respectively.

CONCLUSION

Nivolumab plus chemotherapy did not significantly improve PFS versus chemotherapy in patients with EGFR-mutated metastatic NSCLC previously treated with EGFR TKIs. No new safety signals were identified.

Author Affiliations

1State Laboratory of Translational Oncology, The Chinese University of Hong Kong, Hong Kong, China; 2Kindai University Faculty of Medicine, Osaka, Japan; 3Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea; 4University of Texas MD Anderson Cancer Center, Houston, TX; 5National Cancer Center Hospital, Tokyo, Japan; 6Institut du Thorax Curie-Montsouris, Institut Curie, Paris, France; 7Division of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Korea; 8Guangdong Lung Cancer Institute, Guangdong Province People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China; 9Massachusetts General Hospital, Harvard Medical School, Boston, MA; 10Taipei Veterans General Hospital, Taipei City, Taiwan; 11Taipei Cancer Center, Taipei Medical University Hospital, Taipei Medical University, Taipei City, Taiwan; 12Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea; 13Chang Gung Memorial Hospital, College of Medicine, Chang Gung University, Taoyuan, Taiwan; 14Mackay Memorial Hospital, Taipei, Taiwan; 15Hunan Cancer Hospital, Changsha, China; 16Kaohsiung Chang Gung Memorial Hospital, Chang Gung University, Kaohsiung City, Taiwan; 17Tan Tock Seng Hospital, Lee Kong Chian School of Medicine, Singapore, Singapore; 18Johns Hopkins University, Baltimore, MD; 19Saiseikai Kumamoto Hospital, Kumamoto, Japan; 20Peking Union Medical College Hospital, Beijing, China; 21Bristol Myers Squibb, Princeton, NJ; 22National Taiwan University Cancer Center, National Taiwan University Hospital, Taipei City, Taiwan

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