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
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.


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

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

Leave a Comment

Your email address will not be published. Required fields are marked *

Related Articles

Perioperative Nivolumab in Resectable Lung Cancer

Perioperative nivolumab (Nivo) showed a 20% 18-month EFPS improvement. This is another option to consider for your patients with stage IIA-IIIB NSCLC. Of note, the study arm received chemo + Nivo x 4 cycles preoperatively, then 12 months of Nivo therapy, and toxicities were as expected.

Read More »

Plasma Proteome–Based Test for First-Line Treatment Selection in Metastatic Non–Small Cell Lung Cancer

FCS medical oncologist and hematologist Ernesto Bustinza-Linares, MD has co-authored an abstract published in the American Society of Clinical Oncology Journal, JCO Precision Oncology, that uncovers a new testing method to determine personalized care options for patients with metastatic non-small cell lung cancer (NSCLC). The abstract’s authors address the limitations of existing guidelines that recommend checkpoint immunotherapy, sometimes in combination with chemotherapy, for treating NSCLC, which often discounts patient variability and immune factors. The findings from the study show that by incorporating additional plasma proteome-based testing, combined with the standard protein inhibitor testing, clear differences in patient outcomes were observed after applying targeted treatments based on the testing results.

Read More »

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)

Adding VEGF inhibitor to PD-1 blocker in addition to chemotherapy is better than a chemotherapy-alone regimen as a second-line therapy after TKI failure. This is true especially in patients with tumors with high PD-L1 expression, with not much besides chemotherapy as second-line therapy for those patients (or other clinical trials) that may be a better option that includes immunotherapy.

Read More »