LBA48 - CCTG BR.31: A global, double-blind placebo-controlled, randomized phase III study of adjuvant durvalumab in completely resected non-small cell lung cancer (NSCLC)

Background

Adjuvant chemotherapy (ACT) improves 5-yr survival by 5% in resected NSCLC (R0-NSCLC), but 60% of patients (pts) relapse and die. The PD-L1 inhibitor durvalumab (D) has proven efficacy in metastatic and unresectable stage III NSCLC, and as a perioperative regimen in resectable NSCLC. We evaluated adjuvant D in early-stage R0-NSCLC in the Canadian Cancer Trials Group (CCTG) BR.31 trial.

Methods

BR.31 recruited pts ≥18 yr with histologically confirmed, resected (RO) stage IB (≥4 cm), II or IIIA NSCLC (AJCC 7^th ed) and PD-L1 tumour cell (TC) expression at 269 sites in 19 countries. Pts were offered optional ACT before 2:1 randomization to D versus placebo (P) (Q4w, 12 mths), stratified by stage, PD-L1 TC status, ACT, treating centre and extent of nodal sampling. Primary endpoint (1⁰ EP): investigator-assessed disease-free survival (DFS) in pts with PD-L1 TC ≥25%, excluding common EGFR or ALK mutations (EGFR-/ALK-). 2⁰ EPs: DFS in EGFR-/ALK- pts with PD-L1 TC ≥1%, all EGFR-/ALK- pts, and overall survival in PD-L1 TC ≥25%, ≥1% and all pts. Safety was assessed in pts receiving ≥1 dose. Statistical analysis used stratified log rank tests with trial wise type I error controlled at 5% (2-sided) via a prespecified hierarchical testing procedure (EGFR-/ALK- subgroups).

Results

1415 pts were randomized and median follow-up was 60 mo. Characteristics of the 1219 (86%) EGFR-/ALK- pts: median age 64 yr, 66% male, 62% with adenocarcinoma, 84% received ACT and 11/56/32% with Stage IB/II/IIIA NSCLC. 1⁰ and 2⁰ DFS EPs are reported in the table. Maximum grade 3-5 AE rates in all randomized pts were similar between arms (D=27% vs P=21%). Table: LBA48

Conclusions

In BR.31, adjuvant D following R0 resection and optional ACT was not associated with significant improvement in DFS outcomes versus P in EGFR-/ALK- pts, regardless of PD-L1 status. Safety was consistent with the known profile of D.

Clinical trial identification

NCT02273375.

Editorial acknowledgement

Legal entity responsible for the study

Canadian Cancer Trials Group.

Funding

AstraZeneca.

Disclosure

G. Goss: Financial Interests, Personal, Invited Speaker: AstraZeneca, Merck. G.E. Darling: Financial Interests, Personal, Invited Speaker, Honorarium 2023, $2000: BMS; Financial Interests, Personal, Stocks/Shares, stocks in multiple companies managed funds - I do not direct buying or selling of shares: multiple. V. Westeel: Financial Interests, Personal, Advisory Board: Roche, BMS, MSD, AstraZeneca, Takeda, Amgen, Pfizer, Lilly, Sanofi, Ipsen; Financial Interests, Institutional, Research Funding: BMS, AbbVie, Roche, Lilly, Fresenius, Boehringer, Novartis, Merck, Daiichi Sankyo, Amgen, Seagen; Financial Interests, Personal, Sponsor/Funding: Roche, Janssen, AstraZeneca, Amgen, BMS, MSD, Sanofi. K. Nakagawa: Financial Interests, Personal, Invited Speaker: Ono Pharmaceutical Co., Ltd., Eli Lilly Japan K.K., AstraZeneca K.K., Chugai Pharmaceutical Co., Ltd., MSD K.K., Pfizer Japan Inc., Nippon Boehringer Ingelheim Co., Ltd., Taiho Pharmaceutical Co., Ltd., Bayer Yakuhin, Ltd., Incyte biosciences Japan, Merck Biopharma Co., Ltd., Janssen Pharmaceutical K.K., Bristol Myers Squibb Company, Medical Mobile Communications co., Ltd, Novartis Pharma K.K., Daiichi Sankyo Co., Ltd., Otuka Pharmaceutical Factory, Inc., M3, Inc., Hisamitsu Pharmaceutical Co., Inc., Global Health Consulting Japan Co., Ltd., The Yomiuri Shimbun; Financial Interests, Personal, Advisory Board: Ono Pharmaceutical Co.,Ltd., Eli Lilly Japan K.K.; Financial Interests, Personal, Writing Engagement: Yodosha Co., Ltd.; Financial Interests, Institutional, Research Grant: Amgen Inc., Bristol Myers Squibb K.K., Chugai Pharmaceutical Co.,Ltd., EP-CRSU Co., Ltd., EPS Corporation., Eisai Co., Ltd., GSK K.K., IQVIA Services Japan K.K., Janssen Pharmaceutical K.K., Kobayashi Pharmaceutical Co., Ltd., MSD K.K., Nippon Boehringer Ingelheim Co.,Ltd., Nippon Kayaku Co.,Ltd., Pra Healthsciences, SRL Medisearch Inc., Syneos Health Clinical K.K., Sanofi K.K., Taiho Pharmaceutical Co.,Ltd., Takeda Pharmaceutical Co.,Ltd., CMIC CO., Ltd., Pfizer R&D Japan G.K., Labcorp Development Japan K.K., Pfizer Japan Inc., Shionogi & Co., Ltd., Otsuka Pharmaceutical Co., Ltd., Astellas Pharma Inc., Ascent Development Services, Eisai Inc., Bayer Yakuhin, Ltd, AstraZeneca K. K., AbbVie Inc., A2 Healthcare Corp., Japan Clinical Cancer Research Organization, Thoracic Oncology Research Group. B. Massuti Sureda: Financial Interests, Personal, Advisory Board: AstraZeneca, BMS, Boehringer Ingelheim; Financial Interests, Personal, Invited Speaker: MSD, Roche; Financial Interests, Institutional, Funding, Research on Tumor Board: BMS; Non-Financial Interests, Principal Investigator: AstraZeneca, MSD; Non-Financial Interests, Advisory Board: ASCO; Non-Financial Interests, Member: IASLC, SEOM; Non-Financial Interests, Leadership Role: SLCG. F. Perrone: Financial Interests, Personal, Advisory Board: AstraZeneca, Eli Lilly, GSK, Boeringher Ingelheim, Pfizer, BMS, Menarini, Roche; Financial Interests, Institutional, Research Grant, Financial support for clinical trials promoted by the NCI Naples: Roche, Bayer, AstraZeneca, Pfizer, Merck; Financial Interests, Institutional, Research Grant, Financial support for phase 1 trials at the NCI Naples: Incyte, Tesaro/GSK; Non-Financial Interests, Leadership Role, President (November 2023 to November 2025): AIOM Associazione Italiana di Oncologia Medica. S. McLachlan: Financial Interests, Personal, Advisory Board: BMS. J.H. Kang: Financial Interests, Personal, Advisory Board: Amgen, AstraZeneca, Merck, Daiichi Sankyo; Financial Interests, Personal, Invited Speaker: Boehringer Ingelheim, Roche, MSD, ONO, Yuhan, Takeda; Financial Interests, Personal, Research Grant: Ono, Daiichi Sankyo, Boehringer Ingelheim; Financial Interests, Personal, Steering Committee Member: Yuhan. Y. Wu: Financial Interests, Personal, Invited Speaker: AstraZeneca, BMS, Boehringer Ingelheim, BeiGene, Hengrui, Merk, MSD, Pfizer, Roche, Sanofi; Financial Interests, Personal, Advisory Board: AstraZeneca, MSD, Takeda, Amgen, Daiichi Sankyo; Financial Interests, Coordinating PI: AstraZeneca, Boehringer Ingelheim, BMS, Hengrui, Merk, MSD, Pfizer, Roche, Eli Lilly; Financial Interests, Steering Committee Member: Sanofi, Yunhan; Non-Financial Interests, Leadership Role: Chinese Thoracic Oncology Group (CTONG); Non-Financial Interests, Other, WCLC 2020 Conference Chair: IASLC; Non-Financial Interests, Leadership Role, Past President: Chinese Society of Clinical Oncology (CSCO); Non-Financial Interests, Other, Editorial Board member of Ann Oncology and ESMO Open: ESMO. A.C. Dingemans: Financial Interests, Institutional, Advisory Board: Roche, Amgen, Bayer, AstraZeneca, Boehringer Ingelheim, Jansen, Mirati; Financial Interests, Institutional, Invited Speaker: Lilly, Jansen; Financial Interests, Institutional, Other, IDMC: Roche; Financial Interests, Institutional, Research Grant: Amgen; Financial Interests, Institutional, Local PI: Lilly, Amgen, Daiichi, JNJ, Mirati; Financial Interests, Institutional, Coordinating PI: Roche; Financial Interests, Institutional, Steering Committee Member: Roche; Non-Financial Interests, Other, Chair EORTC lung cancer group: EORTC; Non-Financial Interests, Member: IASCL, ASCO, AACR. R. Dziadziuszko: Financial Interests, Personal, Advisory Board: Roche, AstraZeneca, Pfizer, Novartis, Takeda, MSD, Bristol Myers Squibb, Bayer; Financial Interests, Personal, Invited Speaker: Boehringer Ingelheim; Financial Interests, Personal and Institutional, Coordinating PI: Roche, AstraZeneca; Financial Interests, Personal and Institutional, Local PI: MSD, Amgen, Celon Pharma, Pfizer, Novartis, Bristol Myers Squibb, Eli Lilly, Loxo; Financial Interests, Personal and Institutional, Other, Subinvestigator and ad hoc Consultant: PDC* line Pharma; Financial Interests, Local PI: OSE Immunotherapeutics; Non-Financial Interests, Institutional, Product Samples: Novartis, Pfizer, AstraZeneca, Roche. M. Okada: Financial Interests, Personal, Speaker’s Bureau: Johnson and Johnson, Chugai, MSD, BMS; Financial Interests, Institutional, Research Funding: Chugai, BMS, AstraZeneca, Taiho. L. Greillier: Financial Interests, Personal, Advisory Board: AbbVie, AstraZeneca, BMS, MSD, Novartis, Sanofi, Takeda, Roche; Financial Interests, Personal, Invited Speaker: Lilly, Pfizer; Financial Interests, Institutional, Local PI: AstraZeneca, AbbVie, BMS, MSD, Novartis, Takeda, Pfizer, Roche, PharmaMar; Financial Interests, Institutional, Coordinating PI: Sanofi. C. Audigier-Valette: Financial Interests, Personal, Advisory Board: Roche, BMS, MSD, Pfizer, AstraZeneca, Sanofi, Janssen, Amgen; Non-Financial Interests, Institutional, Other: IFCT, Advisory Role, Scientific committee GFPC, Principal Investigator Edimark, Member of Board of Directors, Editorial Committee Lettre du cancérologue Actualités en oncologie thoracique 3C VAR OUEST, Member of Board of Directors, President. S. Sugawara: Financial Interests, Personal, Other, Lecture fee: AstraZeneca, Chugai Pharma, Nippon Boehringer Ingelheim, Taiho Pharmaceutical, Pfizer, Lilly, Novartis, Bristol Myers Squibb, Ono Pharmaceutical, MSD K.K, Kyowa Kirin, Takeda, Nippon Kayaku, Merck, Amgen, Thermo Fisher Scientific; Financial Interests, Personal, Other, Lecture Fee: Eisai, Sysmex; Financial Interests, Institutional, Local PI: AstraZeneca, Chugai Pharma, MSD K.K, Daiichi Sankyo, Bristol Myers Squibb, AnHeart, Ono Pharmaceutical, Nippon Boehringer Ingelheim, AbbVie, Parexel International, Amgen, Taiho Pharmaceutical, Accerise, A2 Healthcare, EPS Corporation, Syneos Health, PPD-SNBL. E. Nadal: Financial Interests, Personal, Advisory Board: Roche, Bristol Myers Squibb, Merck Sharp Dohme, Boehringer Ingelheim, Lilly, Pfizer, Merck Serono, Daiichi Sankyo, AstraZeneca, Takeda, Amgen, Sanofi, Qiagen, Janssen, Regeneron, Pierre Fabre; Financial Interests, Personal, Invited Speaker: Roche, Bristol Myers Squibb, Merck Sharp Dohme, Lilly, Pfizer, Sanofi, AstraZeneca, Takeda, Amgen, Qiagen, Janssen, Daiichi, Illumina; Financial Interests, Personal and Institutional, Funding, Clinical trial funded by Roche: Roche; Financial Interests, Personal and Institutional, Funding, Merck Serono funded a clinical trial: Merck Serono; Financial Interests, Personal and Institutional, Funding, BMS funded a clinical trial: Bristol Myers Squibb; Non-Financial Interests, Advisory Role: Pfizer, Roche, Apollomics, Transgene; Other, Member of the Steering Committee: Spanish Lung Cancer Group (GECP). M.R. Stockler: Financial Interests, Institutional, Research Grant, DASL: Bayer; Financial Interests, Institutional, Research Grant, Enzamet & Enzarad: Astellas; Financial Interests, Institutional, Research Grant, Keypad: Amgen, MSD; Financial Interests, Institutional, Research Grant, Nivorad: BMS; Financial Interests, Institutional, Research Grant: Pfizer, Roche; Financial Interests, Institutional, Research Grant, Adele: BeiGene; Financial Interests, Institutional, Research Grant, PARAGON2: Novartis; Financial Interests, Institutional, Other, Study Drug for Cannabis CINV Trial: Tilray; Financial Interests, Institutional, Research Grant, Illuminate, Phaedra,: AstraZeneca. All other authors have declared no conflicts of interest.