1264MO - IMpower010: Exploratory analysis of disease-free survival (DFS) by TGFβ cancer-associated fibroblast (CAF) gene signature expression in patients (pts) with resected NSCLC treated with atezolizumab (atezo) or best supportive care (BSC)

Background

CAFs are an important component of the tumour microenvironment. TGFβ-induced CAFs have been associated with poor prognosis in several indications. In IMpower010, adjuvant atezo showed significant DFS benefit vs BSC in resected early-stage NSCLC after chemotherapy (chemo), leading to approval of atezo after platinum-based chemo for resected (R0) PD-L1 TC ≥1% or ≥50% (SP263) stage II-IIIA NSCLC. We report results from exploratory analyses to identify predictive biomarkers for atezo outcomes using IMpower010 RNA sequencing (RNAseq) data.

Methods

The IMpower010 study design and primary data have been reported ( Felip, Lancet 2021 ). The predictive effects of features including cell-type and -state gene signatures for DFS (atezo vs BSC) were evaluated from baseline (resection) tumour samples. Relevant features were identified based on variable importance scores calculated by generalised random forests method. Median DFS was estimated using Kaplan-Meier curves; HRs were estimated by Cox regressions.

Results

Of the 1005 randomised pts (ITT), 500 comprised the RNAseq biomarker-evaluable population. The TGFβ CAF gene signature had the highest variable importance. DFS HRs (95% CI) were 0.54 (0.37, 0.80) and 0.94 (0.63, 1.41) in the TGFβ CAF-high (≥ median) and -low (< median) populations (Table). Improved outcomes with atezo vs BSC in the TGFβ CAF-high population were driven by shorter DFS in the BSC arm. Baseline characteristics were generally balanced across populations.

Conclusions

Exploratory analyses of IMpower010 RNAseq data showed that the TGFβ CAF-high population had improved DFS with atezo vs BSC, regardless of histology or PD-L1 expression level. These data suggest that after surgical resection, pts with enrichment of the TGFβ CAF gene signature may have improved DFS after adjuvant atezo vs BSC. Table: 1264MO

BEP, biomarker evaluable population; NR, not reached; TGFβ, transforming growth factor beta.

Clinical trial identification

NCT02486718.

Editorial acknowledgement

Medical writing support for this abstract, furnished by Kia C. E. Walcott, PhD, of Health Interactions, Inc., was provided by F. Hoffmann-La Roche Ltd, Basel, Switzerland.

Legal entity responsible for the study

F. Hoffmann-La Roche, Ltd.

Funding

F. Hoffmann-La Roche, Ltd.

Disclosure

N.K. Altorki: Financial Interests, Institutional, Research Grant, Grants or Contracts: AstraZeneca, Janssen; Other, Personal, Leadership Role, IMpower010 Steering Committee: Roche. M. Reck: Financial Interests, Personal, Invited Speaker: Amgen, AstraZeneca, BMS, Boehringer Ingelheim, Lilly, MSD, Merck, Novartis, Regeneron, Roche, Sanofi; Financial Interests, Personal, Advisory Board: Amgen, AstraZeneca, BMS, BioNTech, Boehringer Ingelheim, Daiichi Sankyo, Gilead, MSD, Mirati, Pfizer, Regeneron, Sanofi, Roche; Financial Interests, Personal, Other, Member of DMSB: Daiichi Sankyo. H. Wakelee: Financial Interests, Personal, Advisory Board, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: Blueprint, Mirati; Financial Interests, Personal, Invited Speaker, Develop and present a series of lectures: Fishawack Facilitate Ltd; Financial Interests, Personal, Invited Speaker, Series of CME lectures: Medscape, Research to Practice; Financial Interests, Personal, Other, Discussion of new data at conferences: Curio Science; Financial Interests, Personal, Invited Speaker, Series of lectures/webinars for PER/OncLive: MJH Holdings; Financial Interests, Personal, Writing Engagement: UpToDate; Financial Interests, Personal, Invited Speaker, CME lecture: Axis Medical Education, Nexus Oncology; Financial Interests, Institutional, Local PI, Clinical Trial Conduct: ACEA Biosciences, Arrys Therapeutics, AstraZeneca/Medimmune, BMS, Clovis Oncology, Novartis, Seagen, Xcovery; Financial Interests, Institutional, Coordinating PI, Clinical Trial Conduct: Celgene; Financial Interests, Institutional, Steering Committee Member, Clinical Trial Conduct: Genentech/Roche, Merck; Financial Interests, Institutional, Local PI, clinical trial conduct: Helsinn; Non-Financial Interests, Officer, President: International Association for the Study of Lung Cancer (IASLC); Non-Financial Interests, Leadership Role, Executive Committee: ECOG-ACRIN. E. Felip: Financial Interests, Personal, Advisory Board: AbbVie, Amgen, AstraZeneca, Bayer, BeiGene, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, F. Hoffmann-La Roche, Gilead, GSK, Janssen, Merck Serono, Merck Sharp & Dohme, Novartis, Peptomyc, Regeneron, Sanofi, Takeda, Turning Point, Pfizer; Financial Interests, Personal, Invited Speaker: Amgen, Daiichi Sankyo, Genentech, Janssen, Medical Trends, Medscape, Merck Serono, PeerVoice, Pfizer, Sanofi, Takeda, Touch Oncology, AstraZeneca, Bristol Myers Squibb, Eli Lilly, F. Hoffmann-La Roche, Merck Sharp & Dohme; Financial Interests, Personal, Member of Board of Directors, Independent member: Grifols; Financial Interests, Institutional, Local PI, Clinical Trial: AstraZeneca AB, AbbVie, Amgen, Bayer Consumer Care AG, BeiGene, Boehringer Ingelheim GmbH, Bristol Myers Squibb International Corporation, Daiichi Sankyo Inc., Exelixis Inc., F. Hoffmann-La Roche Ltd., Genentech Inc., GSK Research and Development Limited, Janssen Cilag International NV, Merck Sharp & Dohme Corp, Merck KGAA, Mirati Therapeutics Inc, Novartis Pharmaceutica SA, Pfizer, Takeda Pharmaceuticals International; Non-Financial Interests, Leadership Role, President (2021-2023): SEOM (Sociedad Espanola de Oncologia Medica); Non-Financial Interests, Member, Member of Scientific Committee: ETOP (European Thoracic Oncology Platform); Non-Financial Interests, Member, Member of the Scientiffic Advisory Committee: CAC Hospital Universitari Parc Taulí. E. Vallieres: Financial Interests, Personal, Advisory Role, Consulting fees: Bristol Myers Squibb; Financial Interests, Personal, Financially compensated role, Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events: Olympus, AstraZeneca, Oncocyte. S. Oizumi: Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Institutional, Research Grant: AbbVie, Amgen, AstraZeneca, Bristol Myers Squibb, Chugai Pharmaceutical, MSD, Pfizer, Sanofi, Taiho Pharmaceutical, Takeda Pharmaceutical. H. Tanaka: Financial Interests, Personal, Invited Speaker: AstraZeneca, Chugai Pharmaceutical, Boehringer Ingelheim, Eli Lilly, MSD, Ono Pharmaceutical, Merck, Novartis, Takeda Pharmaceutical, Pfizer, DaiIchi Sankyo Pharmaceutical, Taiho Pharmaceutical, Bristol Myers Squibb, Eisai; Financial Interests, Institutional, Local PI: Chugai Pharmaceutical, Merck, AstraZeneca, MSD, Eli Lilly, Ono Pharmaceutical, Bristol Myers Squibb, Merck, Takeda Pharmaceutical, Taiho Pharmaceutical, Pfizer, Daiichi Sankyo Pharmaceutical, AbbVie, Amgen, Janssen Pharmaceutical. S. Novello: Financial Interests, Personal, Invited Speaker: AZ, MSD, Eli Lilly, Novartis, BeiGene, Amgen; Financial Interests, Personal, Advisory Board: BI, BMS, Pfizer, Takeda, Roche, Sanofi, Amgen; Financial Interests, Institutional, Coordinating PI, IIT: MSD, BI; Non-Financial Interests, Leadership Role, president of this european advocacy: WALCE. S. McCune: Financial Interests, Personal, Speaker’s Bureau: Bristol Myers Squibb; Financial Interests, Personal, Research Funding: Bristol Myers Squibb, Roche/Genentech; Financial Interests, Institutional, Other: Roche. H. Li, V.A. McNally: Financial Interests, Personal, Full or part-time Employment: Roche; Financial Interests, Personal, Stocks/Shares: Roche. L. Molinero, E. Bennett, B.J. Gitlitz, M. Ballinger, B. Nabet, M.K. Srivastava: Financial Interests, Personal, Full or part-time Employment: Genentech; Financial Interests, Personal, Stocks/Shares: Roche. S. Müller: Financial Interests, Personal, Full or part-time Employment: Roche; Financial Interests, Personal, Stocks/Shares: Genentech. C. Zhou: Financial Interests, Personal, Invited Speaker, Honoraria: Eli Lily, Roche, Sanofi, Qilu Pharma, Hengrui, Innovent Biologics, C-Stone, Luye Pharma, TopAlliance Biosciences Inc; Financial Interests, Personal, Invited Speaker: BI; Financial Interests, Personal, Invited Speaker: MSD; Financial Interests, Personal, Advisory Board, Advisor: Amoy Diagnostics. All other authors have declared no conflicts of interest.