Abstract 41P
Background
Tumor histologic subtype (THS) has been reported to be a prognostic indicator for NSCLC; the solid subtype is associated with poor prognosis. 1L N + I has demonstrated durable, long-term clinical benefit vs chemotherapy (C) in pts with mNSCLC. Here we report exploratory analyses of overall survival (OS) with 1L N + I and association of biomarkers by mNSCLC THS using data from the CheckMate (CM) 227 and 568 trials.
Methods
THS was assessed in pts with evaluable mNSQ-NSCLC tissue in CM 227 Part 1 (NCT02477826; ph 3; N + I vs C; n = 675) and in CM 568 Part 1 (NCT02659059; ph 2; N + I, single arm; n = 170) by 3 independent pathologists using a modified version of the WHO NSCLC classification system. Samples were classified as solid, acinar, or other THS per consensus on the predominant THS. Exploratory assessments included OS, tumor PD-L1, TMB, select somatic mutations (muts; TP53, KRAS, and STK11; FoundationOne CDx™), and gene expression analysis (GEA) by THS.
Results
Baseline characteristics were generally consistent across THS and treatment groups. Minimum follow-up was 61.3 and 61.2 mo in CM 227 and 568, respectively. In both trials, greater OS benefit was observed in N + I-treated pts with solid vs acinar THS (CM 227: HR 0.60, 95% CI 0.45–0.80; CM 568: HR 0.67, 95% CI 0.44–1.02; table). In contrast, among C-treated pts, OS was similar in pts with solid or acinar THS in CM 227 (HR 1.01, 95% CI 0.77–1.32). Further exploratory analysis identified a trend toward higher tumor PD-L1 expression and TMB in pts with solid vs acinar THS (table). A higher frequency of TP53 muts and lower frequencies of KRAS and STK11 muts were also observed in the solid THS. These results and findings from GEA by THS will be presented.
Table: 41PBiomarkers and OS by THS
| CM 227 Part 1aN + I | CM 568 Part 1aN + I | |||
|---|---|---|---|---|
| Solid (n = 192) | Acinar (n = 91) | Solid (n = 77) | Acinar (n = 48) | |
| Median tumor PD-L1 expression, % (range) | 50 (0–100) | 1 (0–100) | 30 (0–100) | 0 (0–80) |
| Median TMB, mut/Mb (range) | 8.8 (0–66.8) | 6.3 (0–44.1) | 10.1 (1.3–98.4) | 5.7 (1.3–17.6) |
| OS | ||||
| Median, mo (95% CI) | 18.7 (13.5–28.4) | 13.3 (10.0–17.1) | 26.5 (14.6–47.3) | 12.9 (8.6–24.0) |
| HR, solid vs acinar (95% CI) | 0.60 (0.45–0.80) | – | 0.67 (0.44–1.02) | – |
| 5-y rate, % (95% CI) | 31.0 (24.9–38.4) | 6.0 (2.6–14.0) | 31.1 (21.9–44.1) | 18.4 (9.9–34.3) |
THS-evaluable pts: CM 227 (N + I and C), 675 pts and CM 568 (N + I), 170 pts; solid, 59% and 45%; acinar, 26% and 28%; other, 10% and 7%; not specified, 5% and 19%, respectively.
Conclusions
Greater long-term OS benefit with N + I was seen in pts with the solid mNSCLC THS, a subgroup with poor prognosis, vs pts with the acinar THS. Exploratory PD-L1, TMB, and mut analysis may provide insight into the clinical benefit of 1L dual immunotherapy by THS.
Clinical trial identification
NCT02477826, NCT02659059.
Editorial acknowledgement
Medical writing and editorial support for the development of this abstract, under the direction of the authors, was provided by Wendy Sacks, PhD, and Michele Salernitano of Ashfield MedComms, an Inizio company, and funded by Bristol Myers Squibb.
Legal entity responsible for the study
Bristol Myers Squibb.
Funding
Bristol Myers Squibb.
Disclosure
H. Borghaei: Financial Interests, Personal, Research Grant: Bristol Myers Squibb, Eli Lilly, Amgen; Financial Interests, Personal, Other, consulting fees: BMS, Eli Lilly, Genentech, Pfizer, Merck, EMD-Serono, Boehringer Ingelheim, AstraZeneca, Novartis, Genmab, Regeneron, BioNTech, Amgen, Axiom, PharmaMar, Takeda, Mirati, Daiichi Sankyo, Guardant, Natera, Oncocyte, BeiGene, iTEO, Jazz Pharmaceuticals, Janssen, Da Volterra; Financial Interests, Personal, Other, honoraria: Amgen, Pfizer, Daiichi Sankyo, Regeneron; Financial Interests, Personal, Other, support for attending meetings and travel: Amgen, BMS, Merck, Eli Lilly, EMD-Serono, Genentech, Regeneron; Financial Interests, Personal, Advisory Board: University of Pennsylvania: CAR T Program, Takeda, Incyte, Novartis; Financial Interests, Personal, Stocks/Shares: Sonnetbio (Stock Options); Inspirna (formerly Rgenix, Stock Options); Nucleai (stock options); Financial Interests, Personal, Writing Engagements, medical writing: BMS, Amgen, AstraZeneca. 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All other authors have declared no conflicts of interest.