1230P - Association between early endpoints and survival outcomes in neoadjuvant treatment of resectable non-small cell lung cancer (NSCLC): A multi-country retrospective study

Background

Meta-analyses have shown longer overall survival (OS) and event-free survival (EFS) with complete and major pathologic response (pCR and MPR) to neoadjuvant therapy for NSCLC. We aimed to further characterize the relationship between pCR/MPR with EFS/OS and between EFS and OS in patients (pts) receiving chemotherapy (CT)/chemoradiotherapy (CRT) based on real-world data from multi-country sites.

Methods

This retrospective study was conducted at 15 sites in the United States, France, and Spain. Pts diagnosed with stage IB-IIIA NSCLC (AJCC 7^th ed.) between Jan 2010 and Dec 2017 and receiving neoadjuvant CT/CRT followed by surgery were eligible. The primary objective was to evaluate the association between early treatment response (pCR and MPR) and survival outcomes (EFS and OS) using patient-level Bayesian random-effects models. Subgroup analyses were performed by age, gender, stage, histology, and type of neoadjuvant therapy. Landmark analyses were used to assess the association between EFS and OS.

Results

A total of 365 pts were included and 76% had stage III disease, 65% received neoadjuvant CT. The pCR rate was 4% and 24% in those treated with CT and CRT, respectively. The MPR rate was 9% and 37% in those treated with CT and CRT, respectively. The median follow-up time was 3.3 years. Pts with pCR had significantly longer OS than pts without pCR (HR 0.44; 95% Credible Interval [CrI] 0.20 – 0.80) and EFS (HR 0.36; 95% CrI 0.17 – 0.64). In pts with MPR vs no MPR, the HR for OS was 0.73 (95% CrI 0.45 – 1.09) and for EFS, the HR was 0.69 (95% CrI 0.46 – 0.99). The associations between pCR and improved OS and EFS were consistent across subgroups and showed improved survival estimates in those treated with neoadjuvant CT (OS HR 0.02 [95% CrI 0.00 – 0.17]; EFS HR 0.14 [95% CrI 0.01 – 0.51]). Landmark analysis of OS by EFS events prior to the 12-month landmark resulted in a HR of 0.32 (95% CrI 0.21 – 0.47).

Conclusions

pCR and MPR were associated with longer EFS and OS in pts with NSCLC receiving neoadjuvant CT/CRT for stage IB-IIIA NSCLC. EFS was also associated with OS. pCR and MPR may serve as useful surrogate endpoints in future clinical trials for this pt population.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Bristol Myers Squibb, Princeton, NJ, USA.

Funding

Bristol Myers Squibb, Princeton, NJ, USA.

Disclosure

M. Provencio Pulla: Financial Interests, Personal, Advisory Board: BMS, MSD, Bayer, Lilly, Roche, Takeda, Janssen; Financial Interests, Personal, Other, Consulting, support for attending meetings and/or travel, honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events: BMS, AstraZeneca, MSD, Roche, Takeda, Eli Lilly, F. Hoffman-La Roche, Janssen, Pfizer, Amgen, Boehringer Ingelheim, Pierre Fabre Pharmaceuticals; Financial Interests, Institutional, Coordinating PI: AstraZeneca, BMS, Takeda, MSD, Roche; Non-Financial Interests, Leadership Role, President of Spanish Lung cancer Group: President; Non-Financial Interests, Leadership Role, Instituto Investigación Sanitaria Puerta de Hierro: Director; Non-Financial Interests, Leadership Role, President: Grupo Oncológico para el Tratamiento de las Enfermedades Linfoides. L. Berry: Financial Interests, Institutional, Other, statistical consulting firm that specializes in the design, conduct, oversight, and analysis of adaptive and platform clinical trials.: Berry Consultants, LLC. M. Quintana: Financial Interests, Institutional, Other, statistical consulting firm that specializes in the design, conduct, oversight, and analysis of adaptive and platform clinical trials.: Berry Consultants, LLC. T.W. LeBlanc: Financial Interests, Personal, Speaker, Consultant, Advisor, Honoraria: AbbVie, Agilix, Agios/Servier, Apellis, Astellas, Beigene, BlueNote, BMS/Celgene, Genentech, Gilead, GSK, Lilly, Meter Health, Novartis, Pfizer, Incyte, Rigel; Financial Interests, Personal, Stocks or ownership: Dosentrx, ThymeCare ; Financial Interests, Personal, Royalties: UpToDate; Financial Interests, Institutional, Research Funding: AbbVie, American Cancer Society, AstraZeneca, BMS, Deverra Therapeutics, Duke University, GSK, Jazz Pharmaceuticals, Leukemia and Lymphoma Society, National Institute of Nursing Research/ National Institutes of Health, Seattle Genetics. C. Mascaux: Financial Interests, Personal, Speaker, Consultant, Advisor, Honoraria: AstraZeneca, Roche, MSD, Sanofi, Pfizer, Takeda, Janssen, Amgen, BMS; Financial Interests, Personal, Other, Travel/Accommodations: Janssen, MSD, Takeda, BMS, Novartis, Amgen. C.M. Bestvina: Financial Interests, Institutional, Research Grant, IIT funding: AstraZeneca, BMS; Financial Interests, Personal, Speaker, Consultant, Advisor: Amgen, AstraZeneca, BMS, Daiichi, EMD Serono, Gilead, Guardant, Mirati, Novocure, Sanofi, Tempus, Turning Point Therapuetics ; Financial Interests, Personal, Other, Travel/Accommodations: BMS, Guardant ; Financial Interests, Personal, Advisory Board: Amgen, AstraZeneca, BMS, Daiichi, EMD Serono, Gilead, Guardant, Mirati, Novocure, Sanofi, Tempus, Turning Point Therapuetics. A.S. Mansfield: Financial Interests, Institutional, Speaker, Consultant, Advisor, grant reviewer: Rising Tide ; Financial Interests, Institutional, Speaker, Consultant, Advisor, expert think tank: TRIPTYCH Health Partners ; Financial Interests, Institutional, Speaker, Consultant, Advisor: Janssen, BeiGene, Chugai Pharmaceutical Co Ltd (Roche), Ideology Health LLC (formerly Health Media), AXIS Medical Education Inc, Johnson & Johnson Global Services, Intellisphere LLC, Answers in CME, Immunocore; Financial Interests, Personal, Speaker, Consultant, Advisor: Antoni van Leeuwenhoek Kanker Instituut, University of Miami Int’l Mesothelioma Symposium; Financial Interests, Personal, Other, Travel/Accommodations: Shanghai Roche; Financial Interests, Institutional, Advisory Board: AbbVie, AstraZeneca, BMS, Genentech/Roche, Janssen, Takeda Oncology, Sanofi Genzyme, Gilead; Non-Financial Interests, Personal, Other, Non-remunerated Director: Mesothelioma Applied Research Foundation; Non-Financial Interests, Personal, Other, Non-remunerated member of board of directors: Friends of Patan Hospital. M. Bates: Financial Interests, Personal, Other, Founder and CEO: LSF Medical Solutions. R.D. Gentzler: Financial Interests, Personal, Advisory Board: AstraZeneca, Takeda, Gilead, Janssen, Mirati, Daiichi Sankyo, Sanofi, Oncocyte, Jazz Pharmaceuticals, Merus; Financial Interests, Personal, Invited Speaker: Clinical Care Options, OncLive, Targeted Oncology, Society for Immunotherapy of Cancer (SITC), MedStar Health, Aptitude Health, American Society of Clinical Oncology (ASCO); Financial Interests, Institutional, Local PI: Janssen, Mirati, Daiichi Sankyo, Bristol Myers Squibb, AstraZeneca, Jounce Therapeutics, Takeda, Bristol Myers Squibb, Merck, Chugai, Amgen, Dizal; Financial Interests, Institutional, Research Grant: Pfizer; Financial Interests, Institutional, Coordinating PI: Mirati; Non-Financial Interests, Leadership Role, Co-chair, Thoracic Working Group: Hoosier Cancer Research Network; Non-Financial Interests, Principal Investigator: NCI ETCTN; Non-Financial Interests, Other, Member of Lung Cancer Scientific Review Committee: American Society of Clinical Oncology, Scientific Review Committee; Non-Financial Interests, Other, Committee Member: NCI Investigational Drug Steering Committee; Non-Financial Interests, Officer, Editor: Journal of Clinical Oncology: Meeting Abstracts; Non-Financial Interests, Other, World Conference on Lung Cancer 2024 Planning Committee: IASLC; Non-Financial Interests, Personal, Other, Travel support for attending meetings for invited speaker: International Association for the Study of Lung Cancer (IASLC); Non-Financial Interests, Personal, Other, Travel to meeting: Tempus, ASCO. N. Girard: Financial Interests, Personal, Invited Speaker: AstraZeneca, BMS, MSD, Roche, Pfizer, Mirati, Amgen, Novartis, Sanofi, Gilead; Financial Interests, Personal, Advisory Board: AstraZeneca, BMS, MSD, Roche, Pfizer, Janssen, Boehringer Ingelheim Novartis, Sanofi, AbbVie, Amgen, Lilly, Grunenthal, Takeda, Owkin, Leo Pharma, Daiichi Sankyo, Ipsen; Financial Interests, Institutional, Research Grant, Local: Roche, Sivan, Janssen; Financial Interests, Institutional, Funding: BMS, Leo Pharma; Financial Interests, Institutional, Research Grant: MSD; Other, Other, Family member is an employee: AstraZeneca. S. Couraud: Financial Interests, Institutional, Funding: ADENE, BD Bioscience, Celgene, Chugai, Janssen, Lilly, Takeda, Transdiag, Volition; Financial Interests, Personal and Institutional, Funding: Amgen, AstraZeneca, BMS, Boehringer Ingelheim MSD, Novartis, Pfizer, Roche, Sanofi; Financial Interests, Personal, Funding: Health Event, Maat Pharma, Pierre Fabre; Non-Financial Interests, Leadership Role: National guidelines in thoracic oncology (ARISTOT); Non-Financial Interests, Member of Board of Directors: Société de Pneumologie de Langue Française, Adene. C.J. Tan: Financial Interests, Institutional, Other, All support for the present publication. Funding was provided to the Pharmacotherapy Outcomes Research Center, Department of Pharmacotherapy Outcomes Research Center, University of Utah to conduct the study.: BMS. M. Wislez: Financial Interests, Personal, Speaker, Consultant, Advisor, Honoraria: Amgen; Financial Interests, Speaker, Consultant, Advisor: AstraZeneca, BMS, F. Hoffman La Roche, Janssen, Merck Serono, Novartis, Pfizer, Takeda, Sanofi, Leopharma; Financial Interests, Speaker, Consultant, Advisor, Honoraria: MSD Oncology, Lilly; Financial Interests, Other, Travel/Accommodations: Janssen, Amgen, MSD, Roche; Financial Interests, Advisory Board: Transgene. C. Calvet: Financial Interests, Personal, Full or part-time Employment: BMS; Financial Interests, Personal, Stocks or ownership: BMS. D.A. Berry: Financial Interests, Personal, Other, co-owner of Berry Consultants, LLC, a company that designs and analyzes results of Bayesian clinical trials for pharmaceutical companies (including Bristol Myers Squibb), medical device companies, National Institutes of Health cooperative groups, patient advocacy groups, and international consortia.: Berry Consultants, LLC. L. Vo: Financial Interests, Personal, Full or part-time Employment: BMS; Financial Interests, Personal, Stocks or ownership: BMS. D. Stenehjem: Financial Interests, Institutional, Research Funding: BMS; Financial Interests, Personal, Speaker, Consultant, Advisor: BMS. All other authors have declared no conflicts of interest.