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, PhD^3,4; Yuichiro Ohe, MD, PhD⁵; Nicolas Girard, MD⁶; Hye Ryun Kim, MD, PhD⁷; Yi-Long Wu, MD⁸; Justin Gainor, MD⁹; Chao-Hua Chiu, MD^10,11; Sang-We Kim, MD, PhD¹²; Cheng-Ta Yang, MD¹³; Chien Liang Wu, MD¹⁴; Lin Wu, MD¹⁵; Meng-Chih Lin, MD¹⁶; Jens Samol, MD^17,18; 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

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.

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

; 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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