A Randomized Phase 2 Trial of Nivolumab Versus Nivolumab-Ipilimumab Combination in EGFR-Mutant NSCLC.

Autor:	Lai GGY; Division of Medical Oncology, National Cancer Centre Singapore, Singapore., Yeo JC; Genome Institute of Singapore, Singapore., Jain A; Division of Medical Oncology, National Cancer Centre Singapore, Singapore., Zhou S; Division of Clinical Trials and Epidemiological Sciences, National Cancer Centre Singapore, Singapore., Pang M; Genome Institute of Singapore, Singapore., Alvarez JJS; Genome Institute of Singapore, Singapore., Sim NL; Genome Institute of Singapore, Singapore., Tan AC; Division of Medical Oncology, National Cancer Centre Singapore, Singapore., Suteja L; Cancer Therapeutics Research Laboratory, National Cancer Centre Singapore, Singapore., Lim TW; Division of Clinical Trials and Epidemiological Sciences, National Cancer Centre Singapore, Singapore., Guo YA; Genome Institute of Singapore, Singapore., Shen M; Division of Medical Oncology, National Cancer Centre Singapore, Singapore., Saw SPL; Division of Medical Oncology, National Cancer Centre Singapore, Singapore., Rohatgi N; Genome Institute of Singapore, Singapore., Yeong JPS; Institute of Molecular and Cell Biology, Singapore., Takano A; Division of Pathology, Singapore General Hospital, Singapore., Lim KH; Division of Pathology, Singapore General Hospital, Singapore., Gogna A; Department of Vascular and Interventional Radiology, Singapore General Hospital, Singapore., Too CW; Department of Vascular and Interventional Radiology, Singapore General Hospital, Singapore., Da Zhuang K; Department of Vascular and Interventional Radiology, Singapore General Hospital, Singapore., Tan WL; Division of Medical Oncology, National Cancer Centre Singapore, Singapore., Kanesvaran R; Division of Medical Oncology, National Cancer Centre Singapore, Singapore., Ng QS; Division of Medical Oncology, National Cancer Centre Singapore, Singapore., Ang MK; Division of Medical Oncology, National Cancer Centre Singapore, Singapore., Rajasekaran T; Division of Medical Oncology, National Cancer Centre Singapore, Singapore., Wang L; Division of Medical Oncology, National Cancer Centre Singapore, Singapore., Toh CK; Division of Medical Oncology, National Cancer Centre Singapore, Singapore., Lim WT; Division of Medical Oncology, National Cancer Centre Singapore, Singapore., Tam WL; Genome Institute of Singapore, Singapore.; Cancer Science Institute of Singapore, National University of Singapore, Singapore., Tan SH; Division of Clinical Trials and Epidemiological Sciences, National Cancer Centre Singapore, Singapore., Skanderup AMJ; Genome Institute of Singapore, Singapore., Tan EH; Division of Medical Oncology, National Cancer Centre Singapore, Singapore., Tan DSW; Division of Medical Oncology, National Cancer Centre Singapore, Singapore.
Jazyk:	angličtina
Zdroj:	JTO clinical and research reports [JTO Clin Res Rep] 2022 Sep 21; Vol. 3 (12), pp. 100416. Date of Electronic Publication: 2022 Sep 21 (Print Publication: 2022).
DOI:	10.1016/j.jtocrr.2022.100416
Abstrakt:	Introduction: Although immune checkpoint inhibitors (ICIs) have dramatically improved outcomes for nononcogene-addicted NSCLC, monotherapy with programmed cell death protein-1 (PD1) inhibition has been associated with low efficacy in the EGFR-mutant setting. Given the potential for synergism with combination checkpoint blockade, we designed a trial to test the activity of combination nivolumab (N)-ipilimumab (NI) in EGFR-mutant NSCLC. Methods: This is a randomized phase 2 study (NCT03091491) of N versus NI combination in EGFR tyrosine kinase inhibitor (TKI)-resistant NSCLC, with crossover permitted on disease progression. The primary end point was the objective response rate, and the secondary end points included progression-free survival, overall survival, and safety of ICI after EGFR TKI. Results: Recruitment ceased owing to futility after 31 of 184 planned patients were treated. A total of 15 patients received N and 16 received NI combination. There were 16 patients (51.6%) who had programmed death-ligand (PDL1) 1 greater than or equal to 1%, and 15 (45.2%) harbored EGFR T790M. Five patients derived clinical benefits from ICI with one objective response (objective response rate 3.2%), and median progression-free survival was 1.22 months (95% confidence interval: 1.15-1.35) for the overall cohort. None of the four patients who crossed over achieved salvage response by NI. PDL1 and tumor mutational burden (TMB) were not able to predict ICI response. Rates of all grade immune-related adverse events were similar (80% versus 75%), with only two grade 3 events. Conclusions: Immune checkpoint inhibition is ineffective in EGFR TKI-resistant NSCLC. Whereas a small subgroup of EGFR-mutant NSCLC may be immunogenic and responsive to ICI, better biomarkers are needed to select appropriate patients. (© 2022 by the International Association for the Study of Lung Cancer.)
Databáze:	MEDLINE
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