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; 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
Anjan J Patel MD

Dr. Anjan Patel's Thoughts

For our NSCLC patients who carry a driver EGFR mutation, there seems to be little/no benefit of the addition of IO therapy to standard chemotherapy in the second line setting.  Prior post hoc analyses showed a trend favoring immunotherapy (IO) therapy in those only having received one prior line of therapy and those with sensitizing EGFR mutations, however this was not confirmed in this randomized phase III study.


The phase III CheckMate 722 trial ( 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).


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).


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.


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

; sup>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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