Clinicopathologic and Genomic Factors Impacting Efficacy of First-Line Chemoimmunotherapy in Advanced NSCLC

化学免疫疗法 医学 内科学 肿瘤科 封锁 胃肠病学 化疗 无进展生存期 癌症 免疫疗法 受体
作者
Joao V. Alessi,Arielle Elkrief,Biagio Ricciuti,Xinan Wang,Alessio Cortellini,Victor R. Vaz,Giuseppe Lamberti,Rosa L. Frias,Deepti Venkatraman,Claudia Angela Maria Fulgenzi,Federica Pecci,Gonzalo Recondo,Alessandro Di Federico,Adriana Barrichello,Hyesun Park,Mizuki Nishino,Grace M. Hambelton,Jacklynn V. Egger,Marc Ladanyi,Subba R. Digumarthy,Bruce E. Johnson,David C. Christiani,Xihong Lin,Justin F. Gainor,W. Marston Linehan,David J. Pinato,Adam J. Schoenfeld,Mark M. Awad
出处
期刊:Journal of Thoracic Oncology [Elsevier BV]
卷期号:18 (6): 731-743 被引量:46
标识
DOI:10.1016/j.jtho.2023.01.091
摘要

Although programmed cell death protein 1 and programmed death-ligand 1 (PD-L1) blockade in combination with platinum-doublet chemotherapy has become a mainstay of first-line treatment for advanced NSCLC, factors associated with efficacy of chemoimmunotherapy (CIT) are not well characterized.In this multicenter retrospective analysis, clinicopathologic and genomic data were collected from patients with advanced NSCLC (lacking sensitizing genomic alterations in EGFR and ALK) and evaluated with clinical outcomes to first-line CIT.Among 1285 patients treated with CIT, a worsening performance status and increasing derived neutrophil-to-lymphocyte ratio in the blood were associated with a significantly reduced objective response rate (ORR), median progression-free survival (mPFS), and median overall survival (mOS). With increasing PD-L1 tumor proportion scores of less than 1%, 1% to 49%, 50% to 89%, and greater than or equal to 90%, there was a progressive improvement in ORR (32.7% versus 37.5% versus 51.6% versus 61.7%, p < 0.001), mPFS (5.0 versus 6.1 versus 6.8 versus 13.0 mo, p < 0.001), and generally mOS (12.9 versus 14.6 versus 34.7 versus 23.1 mo, p = 0.009), respectively. Of 789 NSCLCs with comprehensive genomic data, NSCLCs with a tumor mutational burden (TMB) greater than or equal to the 90th percentile had an improved ORR (53.5% versus 36.4%, p = 0.004), mPFS (10.8 versus 5.5 mo, p < 0.001), and mOS (29.2 versus 13.1 mo, p < 0.001), compared with those with a TMB less than the 90th percentile. In all-comers with nonsquamous NSCLC, the presence of an STK11, KEAP1, or SMARCA4 mutation was associated with significantly worse ORR, mPFS, and mOS to CIT (all p < 0.05); this was also observed in the KRAS-mutant subgroup of NSCLCs with co-occurring mutations in STK11, KEAP1, or SMARCA4 (all p < 0.05). In KRAS wild-type NSCLC, KEAP1 and SMARCA4 mutations were associated with a significantly shorter mPFS and mOS to CIT (all p < 0.05), but STK11 mutation status had no significant impact on mPFS (p = 0.16) or mOS (p = 0.38).In advanced NSCLC, better patient performance status, low derived neutrophil-to-lymphocyte ratio, increasing PD-L1 expression, a very high TMB, and STK11/KEAP1/SMARCA4 wild-type status are associated with improved clinical outcomes to first-line CIT.
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