First-line nivolumab plus ipilimumab combined with two cycles of chemotherapy in advanced non-small cell lung cancer: a subanalysis of Asian patients in CheckMate 9LA

Thomas John,Makoto Maemondo,Abderrahim Oukessou,Takeshi Hisada,Yuki Misumi,Satoshi Ikeda,Hiroshi Sakai,Yoshiro Nakahara,Kazuo Kasahara,Shun Lu,Ang Li,Masayuki Takeda,Helong Zhang,Katsuyuki Hotta,Yuki Sato,Koichi Minato,Miyako Satouchi,Hiroyasu Kaneda,Ying Cheng

doi:10.1007/s10147-022-02120-0

Abstract

BackgroundCheckMate 9LA, a phase 3, randomized, open-label study in first-line advanced non-small cell lung cancer (NSCLC), showed significantly improved overall survival (OS) with nivolumab plus ipilimumab combined with 2 cycles of chemotherapy versus chemotherapy alone (4 cycles). We present results for the Asian subpopulation enrolled in Japan and China.MethodsPatients aged ≥ 18 years with treatment-naive, histologically confirmed stage IV or recurrent NSCLC, Eastern Cooperative Oncology Group performance status 0–1 and no sensitizing EGFR/ALK mutations were randomized 1:1 to nivolumab [360 mg every 3 weeks (Q3W)] plus ipilimumab (1 mg/kg Q6W) combined with chemotherapy (Q3W for 2 cycles), or chemotherapy alone (Q3W for 4 cycles). Primary endpoint was OS; secondary endpoints included progression-free survival (PFS) and objective response rate (ORR).ResultsTwenty-eight patients received nivolumab plus ipilimumab combined with chemotherapy and 30 received chemotherapy. At a minimum follow-up of 12.7 months, median OS was not reached with nivolumab plus ipilimumab combined with chemotherapy versus 13.3 months with chemotherapy [hazard ratio (HR) 0.33; 95% confidence interval (CI) 0.14–0.80]. Median PFS was 8.4 versus 5.4 months (HR 0.47; 95% CI 0.24–0.92) and ORR was 57% versus 23%, respectively. Grade 3–4 treatment-related adverse events were observed in 57% versus 60% of patients, respectively.ConclusionConsistent with results in the all randomized population, nivolumab plus ipilimumab combined with chemotherapy improved efficacy in the Asian subpopulation versus chemotherapy alone and had a manageable safety profile, supporting its use as first-line treatment for advanced NSCLC in Asian patients.

Highlights

Clinical trials of immunotherapy regimens have demonstrated improvements in clinical outcomes over traditional chemotherapy for patients with advanced non-small cell lung cancer (NSCLC) [1–5]
progressionfree survival (PFS) per blinded independent central review (BICR) in Asian patients was improved with nivolumab plus ipilimumab combined with chemotherapy versus chemotherapy alone
Among Asian patients with advanced NSCLC in CheckMate 9LA, first-line treatment with nivolumab plus ipilimumab combined with 2 cycles of chemotherapy provided clinically meaningful overall survival (OS) benefit and improved PFS and objective response rate (ORR) versus chemotherapy alone, consistent with the results observed in the all randomized patient population [median OS, 15.6 versus 10.9 months (HR 0.66; 95% confidence interval (CI) 0.55–0.80) at a minimum follow-up of 12.7 months; median PFS, 6.7 versus 5.0 months (HR 0.68, 95% CI 0.57–0.82); ORR, 38% versus 25%] [16]

Summary

Introduction

Clinical trials of immunotherapy regimens have demonstrated improvements in clinical outcomes over traditional chemotherapy for patients with advanced non-small cell lung cancer (NSCLC) [1–5]. CheckMate 9LA (NCT03215706), a phase 3, randomized, open-label study in first-line advanced NSCLC, showed significantly improved overall survival (OS), progression-free survival (PFS), and objective response rate (ORR) with nivolumab plus ipilimumab combined with 2 cycles of chemotherapy versus 4 cycles of chemotherapy alone, with a manageable safety profile [16, 17]. These data led to the approval of nivolumab plus ipilimumab combined with chemotherapy (2 cycles) in many countries, including the United States, the European Union, and several Asian countries such as Japan, South Korea, Taiwan, and Singapore, as first-line treatment for patients with metastatic or recurrent NSCLC, with no EGFR or ALK genomic tumor aberrations [7, 8, 18–22]. Conclusion Consistent with results in the all randomized population, nivolumab plus ipilimumab combined with chemotherapy improved efficacy in the Asian subpopulation versus chemotherapy alone and had a manageable safety profile, supporting its use as first-line treatment for advanced NSCLC in Asian patients

Methods

Results

Conclusion