LBA3 - Sites of relapse and subsequent therapy in the BR.31 phase III study of durvalumab vs placebo in resected stage IB-IIIA NSCLC

Background

Adjuvant chemotherapy (ACT) improves 5-yr survival by 5% in completely resected NSCLC, but 60% of patients (pts) relapse and die. We analyzed the sites of first relapse and post-relapse treatments in the BR.31 study.

Methods

BR.31 recruited pts with resected stage IB (≥4 cm), II or IIIA NSCLC who were offered ACT before 2:1 randomization to D vs P (Q4w, 12 months), stratified by stage, PD-L1 tumour cell expression, ACT, centre, and extent of nodal sampling. Primary endpoint was disease-free survival (DFS) in pts with PD-L1 ≥25%, excluding common EGFR mutations or ALK translocations (EGFR-/ALK-). Secondary endpoints included: DFS in EGFR-/ALK- pts with PD-L1 ≥1% and all EGFR-/ALKpts, and overall survival in EGFR-/ALK- pts with PD-L1 ≥25% and ≥1%, and all EGFR-/ALK- pts using a prespecified hierarchical testing procedure. Median DFS follow-up was 60 months.

Results

As previously reported, adjuvant D did not improve DFS in EGFR-/ALK- NSCLC, regardless of PD-L1 status (for the primary population: HR=0.93 [0.71-1.25], p=0.64).

The most frequent second primary cancer was lung cancer (5 in.each arm). Among EGFR-/ALK- PD-L1≥25% patients with distant relapse, 73/80 (91%) in the D arm and 36/37 (97%) in the P arm received subsequent treatment, of whom 21/73 (29%) assigned to D and 17/36 (47%) to P received subsequent immunotherapy. Among patients with only locoregional relapse, 22/25 (88%) on D and 13/15 (87%) on P were subsequently treated with surgery or radiotherapy.

Relapses and second primary cancers by arm

Conclusions

Adjuvant D did not reduce the frequency or alter pattern of relapses. As anticipated, fewer patients on the D arm received immunotherapy for distant relapse.

Clinical trial identification

NCT02273375.

Editorial acknowledgement

Legal entity responsible for the study

Canadian Cancer Trials Group.

Funding

AstraZeneca.

Disclosure

V. Westeel: Financial Interests, Personal, Advisory Board: Roche, BMS, MSD, AstraZeneca, Takeda, Amgen, Pfizer, Lilly, Sanofi, Ipsen; Financial Interests, Institutional, Research Grant: BMS, AbbVie, Roche, Lilly, Fresenius, Boehringer Ingelheim, Novartis, Merck, Daiichi Sankyo, Amgen, Seagen; Financial Interests, Personal, Sponsor/Funding: Roche, Janssen, AstraZeneca, Amgen, BMS, MSD, Sanofi. G. Goss: Financial Interests, Personal, Advisory Board, I have participated in advisory boards for AstraZeneca: AstraZeneca; Financial Interests, Personal, Invited Speaker, I gave a talk on immunotherapy in NSCLC: Merck; Non-Financial Interests, Personal, Principal Investigator, I am the PI of the BR.31 trial in early stage NSCLC: Canadian Cancer Trials Group. G. 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. 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, Yodosha 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, 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, Research Grant, Research on Tumor Board: BMS; Non-Financial Interests, Personal, Principal Investigator: AstraZeneca, MSD; Non-Financial Interests, Personal, Advisory Board, ASCO: ASCO; Non-Financial Interests, Personal, Member: IASLC, IASLC SEOM; Non-Financial Interests, Personal, Leadership Role: SLCG. F. Perrone: Financial Interests, Personal, Advisory Board: AstraZeneca, Eli Lilly, GSK, Boehringer 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, Personal, Leadership Role, President (November 2023 to November 2025): AIOM Associazione Italiana di Oncologia Medica. S. McLachlan: Financial Interests, Personal, Advisory Board, Member advisory board for upper gastrointestinal cancers: Bristol Myers Squibb; Financial Interests, Personal, Advisory Board, Member Advisory committee for upper gastrointestinal cancers: BeiGene. 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, Yuhan; Financial Interests, Personal, Research Grant: ONO, Daiichi Sankyo, Boehringer Ingelheim. Y. Wu: Financial Interests, Personal, Invited Speaker: AstraZeneca, BMS, Boehringer Ingelheim, BeiGene, Hengrui, Merk, MSD, Pfizer, Roche, Sanofi, AstraZeneca, Boehringer Ingelheim, BMS, Hengrui, Merk, MSD, Pfizer, Roche, Sanofi, Yunhan, Eli Lilly; Financial Interests, Personal, Advisory Board: AstraZeneca, MSD, Takeda, Amgen, Daiichi Sankyo; Non-Financial Interests, Personal, Leadership Role: Chinese Thoracic Oncology Group (CTONG); Non-Financial Interests, Personal, Other, WCLC 2020 Conference Chair: IASLC; Non-Financial Interests, Personal, Leadership Role, Past President: Chinese Society of Clinical Oncology (CSCO); Non-Financial Interests, Personal, 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, Johnson & Johnson, Boehringer Ingelheim, Pfizer, MSD; Financial Interests, Institutional, Invited Speaker: Lilly, Eli Lilly, Lilly, Amgen, Daiichi Sankyo, Roche, Roche, JNJ, Mirati, Bayer, Eli Lilly, Amgen; Financial Interests, Institutional, Other, IDMC: Roche; Financial Interests, Institutional, Expert Testimony: Mirati; Financial Interests, Institutional, Research Grant: Amgen; Non-Financial Interests, Personal, Other, Chair EORTC lung cancer group: EORTC; Non-Financial Interests, Personal, Member: IASLC, ASCO, AACR, ERS. R. Dziadziuszko: Financial Interests, Personal, Advisory Board: Roche, AstraZeneca, Pfizer, MSD, Bristol Myers Squibb, GSK, Jansen, Amgen; Financial Interests, Personal, Officer, Member of Scientific Board: Polish Agency for Medical Research (ABM); Financial Interests, Personal and Institutional, Invited Speaker: Roche, AstraZeneca, MSD, Amgen, Celon Pharma, Pfizer, Novartis, Bristol Myers Squibb, Eli Lilly, Loxo, Ryvu Therapeutics, Boehringer Ingelheim; Financial Interests, Personal and Institutional, Other, Subinvestigator and ad hoc Consultant: PDC* line Pharma; Financial Interests, Personal, Invited Speaker: OSE Immunotherapeutics; Non-Financial Interests, Institutional, Product Samples: Pfizer, Novartis; Non-Financial Interests, Personal, Member: American Society of Clinical Oncology, Polish Society of Oncology, Polish Society of Clinical Oncology, Polish Society of Radiation Oncology, Academia Europea, European Society for Radiotherapy and Oncology. M. Okada: Financial Interests, Personal, Speaker’s Bureau: Johnson and Johnson, Chugai, MSD, BMS; Financial Interests, Institutional, Research Grant: 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, Invited Speaker: AstraZeneca, AbbVie, BMS, MSD, Novartis, Sanofi, Takeda, Pfizer, Roche, PharmaMar. C. Audigier-Valette: Financial Interests, Personal, Advisory Board: Roche, BMS, MSD, Pfizer, AstraZeneca, Sanofi, Janssen, Amgen; Non-Financial Interests, Personal, Advisory Role: IFCT; Non-Financial Interests, Personal, Other, Scientific committee: GFPC; Non-Financial Interests, Personal, Principal Investigator: Edimark; Non-Financial Interests, Personal, Member, Member of Board of Directors: Editorial Committee Lettre du cancérologue Actualités en oncologie thoracique 3C VAR OUEST. 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, Invited Speaker: 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, Genmab, Apollomics; Financial Interests, Personal, Invited Speaker: Roche, Bristol Myers Squibb, Merck Sharp Dohme, Lilly, Pfizer, Sanofi, AstraZeneca, Takeda, Amgen, Qiagen, Janssen, Daiichi Sankyo, 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, Personal, Advisory Role: Pfizer, Roche, Transgene; Other, Personal, 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.