439P - Standardization of endpoints in early NSCLC randomized clinical trials (RCTs): The DATECAN initiative

Background

Immune-checkpoint (ICIs) and tyrosine-kinase inhibitors (TKIs) have been recently tested in early (neoadjuvant and adjuvant) NSCLC RCTs, with promising results. However, heterogeneity in definition of key efficacy endpoints (EE) represents an issue impairing statistical results. The goal of this project was to standardize definition of EE commonly used in early NSCLC RCTs via an international, multi-step consensus process.

Methods

To identify EE, a literature review was first conducted on RCTs (from 2018 to 2022) evaluating ICIs or TKIs as experimental drug for early NSCLC. An international multidisciplinary panel of experts (N=79) proposed recommendations for the definitions of EE in the (neo) adjuvant setting based on a modified DELPHI consensus method (up to two rounds of rating and two virtual meetings). Invited members were highly qualified (75% current principal investigators, 21 y of median experience), belonged to key professional networks and represented all geographic areas.

Results

In adjuvant setting, 5 EE with 12 events were identified. In neoadjuvant setting, 6 EE with 19 events + 2 binary EE were identified. 1^st round of rating (from February to March 2023) concluded with lack of consensus for all events. 2^nd round of rating (from May to August 2023) led to consensus for 27/60 (adjuvant) and 31/122 events (neoadjuvant) and consensus on pathological Complete Response (pCR). EE that reached consensus are summarized in the table. Clinical events discussed for each EE were: loco-regional/distant event, new primary lung tumour or other than lung, initiation of other anticancer treatment, causes of death, end of treatment due to toxicity or to other causes. Due to redundancy with DFS, experts agreed that RFS and TTR should no longer be used in both settings.

Conclusions

This is the first international consensus on standardized definitions of EE for early NSCLC RCTs, whose use should facilitate comparisons of trial results and enhance quality of trial design and reporting.

Legal entity responsible for the study

Gustave Roussy Institut.

Funding

Has not received any funding.

Disclosure

M.C. Garassino: Financial Interests, Personal, Advisory Board: Eli Lilly, SeaGen International GmbH, Eli Lilly, Incyte, GSK, Bayer Healthcare Pharmaceuticals, Blueprint Medicines, AstraZeneca and Daiichi Sankyo Oncology Teams, Roche, Daiichi Sankyo, Mirati Therapeutics, Inc, Daiichi Sankyo/AstraZeneca, AstraZeneca Poland, Daiichi Sankyo, Inc., MSD, Eli Lilly, Pfizer, AstraZeneca/MedImmune, Sanofi Genzyme corporation, Sanofi/Prex, Regeneron Pharmaceuticals, Eli Lilly, Mirati Therapeutics, Inc., Janssen Pharmaceutical, io biotech, Merck, Novocure, Nuvation, Pfizer, Revolution Medicine, Roche, Merck, AstraZeneca, Bayer, AstraZeneca, Bristol Myers Squibb, Daiichi Sankyo, Gilead, Mirati; Financial Interests, Personal, Invited Speaker: WebMD, WebMD Oncology/Takeda, MSD Italia, Srl, Grupo Pacifico-Secretaria Técnica ICAPEM/AstraZeneca, S. O.S S.r.l, Medscape, ecancer, Ideology, Gilead, Daiichi Sankyo; Financial Interests, Personal, Invited Speaker, Global Experts Meeting: AstraZeneca; Financial Interests, Personal, Other, AstraZeneca Spain: Invitation to a lung cancer investigator meeting: AstraZeneca; Financial Interests, Personal, Advisory Board, Advisory Boards: Takeda, Daiichi Sankyo, BeiGene; Financial Interests, Personal, Other, PACIFIC-R Global Scientific Committee: AstraZeneca; Financial Interests, Personal, Other, Steering Committee member and Co-chair at the AstraZeneca Lung Cancer Summit 2019: AstraZeneca; Financial Interests, Personal, Other, MK-3475 KN671 Steering Committee.: MSD; Financial Interests, Personal, Other, Pacific 6 International Coordinating Investigator: AstraZeneca; Financial Interests, Personal, Other, Janssen Scientific Advisory Board and Therapeutic Area Steering Committee Meeting on Lung Cancer: Janssen; Financial Interests, Personal, Expert Testimony: AstraZeneca UK; Financial Interests, Personal, Other, Pfizer Global Lung Cancer Educational Programme - Steering Committee: Pfizer; Financial Interests, Personal, Other, Seattle Genetics Lung Cancer Platform Study: Seattle Genetics; Financial Interests, Personal, Other, GSK Lung Cancer Global Council: GSK; Financial Interests, Personal, Other, PACIFIC-R Scientific Committee: AstraZeneca UK; Financial Interests, Personal, Other, GSK-Garassino-ZEAL Steering Committee 2020–23: GSK; Financial Interests, Personal, Advisory Board, Advisory Board: AbbVie, Abion, Bayer; Financial Interests, Personal, Advisory Board, Advisory boards: Merck, Sanofi, Gilead; Financial Interests, Personal, Invited Speaker, Satellite Symposium: Merck; Financial Interests, Personal, Invited Speaker, Invited speaker: Medscape; Financial Interests, Personal, Advisory Board, Invited speaker: OncoHost; Financial Interests, Personal, Advisory Board, Advisor: Boehringer Ingelheim; Financial Interests, Personal, Invited Speaker, Member of the MK-3475 KN671 Steering Committee (KEYNOTE-671): MSD; Financial Interests, Personal, Invited Speaker, Coordinating investigator for the MK-3475 KEYNOTE 189: MSD; Financial Interests, Personal and Institutional, Invited Speaker, Pacific 6 Steering Committee and International Coordinating Investigator: AstraZeneca; Financial Interests, Institutional, Invited Speaker, Steering Committee ML41118 Roche: Roche; Financial Interests, Institutional, Invited Speaker, TURNING POINT: Bayer; Financial Interests, Institutional, Invited Speaker, A Phase 1: Janssen; Financial Interests, Institutional, Invited Speaker, Array 818–202: Pfizer; Financial Interests, Institutional, Invited Speaker, PAPILLON Study: Janssen; Financial Interests, Institutional, Invited Speaker, Phase II: Celgene Corporation, Spectrum Pharmaceuticals, Merck Serono; Financial Interests, Institutional, Invited Speaker: Amgen; Financial Interests, Institutional, Invited Speaker, Phase 3: Bluprint; Financial Interests, Institutional, Invited Speaker, Phase III: Amgen, GSK Research & Development Ltd., Novartis; Financial Interests, Institutional, Invited Speaker, Phase III - CEACAM5: Sanofi; Financial Interests, Institutional, Invited Speaker, Phase I-JNJ-61186372, a Human Bispecific EGFR and cMet Antibody: Janssen; Financial Interests, Institutional, Invited Speaker, Phase 3 Study RESILIENT: Ipsen Bioscience Inc.; Financial Interests, Institutional, Invited Speaker, Phase II - SAVANNAH: AstraZeneca S.p.A.; Financial Interests, Institutional, Invited Speaker, phase III NEOCOAST: MedImmune LCC; Financial Interests, Institutional, Invited Speaker, Phase II - coast: MedImmune LCC; Financial Interests, Institutional, Invited Speaker, Phase III - ADRIATIC: AstraZeneca; Financial Interests, Institutional, Invited Speaker, Phase III (CANOPY-1): Novartis; Financial Interests, Institutional, Invited Speaker, Phase 1b: Exelixis Inc.; Financial Interests, Institutional, Invited Speaker, Phase 3-GO40241: Roche; Financial Interests, Institutional, Invited Speaker, Phase IIICASPIAN: AstraZeneca; Financial Interests, Institutional, Invited Speaker, MK3475-091 - PEARLS: Merck; Financial Interests, Institutional, Invited Speaker, Phase III - ROCHE GO29431: Roche; Financial Interests, Institutional, Invited Speaker, Phase III CA209-017: BMS; Financial Interests, Institutional, Invited Speaker, Phase III - ARCTIC: AstraZeneca; Financial Interests, Institutional, Invited Speaker, Phase III - AURA 3: AstraZeneca AB; Financial Interests, Institutional, Invited Speaker, Phase III CA209-057: BMS; Financial Interests, Institutional, Invited Speaker, OPEL/2014/14/067: Otsuka Pharmaceutical Italy S.r.l.; Financial Interests, Institutional, Invited Speaker, Phase II - VISION: Merck KGaA; Financial Interests, Institutional, Invited Speaker, Phase III MK-3475-715: Incyte Corporation; Financial Interests, Institutional, Invited Speaker, Phase 1/2 (TRIDENT-1): Turning Point Therapeutics, Inc.; Financial Interests, Institutional, Invited Speaker, HERTHENA-Lung01: A Phase 2: Daiichi Sankyo Development Ltd.; Financial Interests, Institutional, Invited Speaker, Phase II ATLANTIC: AstraZeneca S.p.A.; Financial Interests, Institutional, Invited Speaker, Clinical trial: Affimed; Financial Interests, Institutional, Invited Speaker, Clinical trial poziotinib: spectrum; Non-Financial Interests, Personal, Principal Investigator, STYLE Trial: Pfizer; Non-Financial Interests, Personal, Principal Investigator, Studio TYME: Eli Lilly; Non-Financial Interests, Personal, Principal Investigator, People: MSD; Non-Financial Interests, Personal, Principal Investigator, FAME trial: Istituto Nazionale dei Tumori; Non-Financial Interests, Personal, Principal Investigator, POST-ALK: Istituto Nazionale dei Tumori; Non-Financial Interests, Personal, Principal Investigator, Bando finalizzata Mesotelioma: Istituto Nazionale dei Tumori; Non-Financial Interests, Personal, Principal Investigator, TERAVOLT: Istituto Nazionale dei Tumori; Non-Financial Interests, Personal, Principal Investigator, Progetto Timoma: Istituto Nazionale dei Tumori; Non-Financial Interests, Personal, Principal Investigator, APOLLO: Istituto Nazionale dei Tumori; Non-Financial Interests, Personal, Principal Investigator, Beverly: Istituto dei Tumori Pascale - Napoli; Non-Financial Interests, Personal, Principal Investigator, IND227: Istituto dei Tumori Pascale - Napoli; Non-Financial Interests, Personal, Principal Investigator, RAMES: GOIRC; Non-Financial Interests, Personal, Principal Investigator, Studio CHANCE: GOIRC; Non-Financial Interests, Personal, Principal Investigator, Creta trial: Sant’Orsola Malpighi - Bologna (Alma Mater Studiorum Università Bologna); Non-Financial Interests, Personal, Principal Investigator, MILES 5: Istituto dei Tumori Pascale - Napoli; Non-Financial Interests, Personal, Principal Investigator, LIPI: Gustave Roussy Parigi Lipi Trial- no profit; Non-Financial Interests, Personal, Principal Investigator: AO Spedali Civili Brescia; Non-Financial Interests, Personal, Principal Investigator, phase III trial: European Thoracic Oncology Platform (ETOP); Non-Financial Interests, Personal, Leadership Role, Honorary President and Founder: Women for Oncology Italy; Non-Financial Interests, Personal, Other, Member of ASCO Scientific Committee (2018–2021): ASCO; Non-Financial Interests, Personal, Leadership Role, Board member: AIOT (Associazione Italiana Oncologia Toracica); Non-Financial Interests, Personal, Member: AIOM, AIOT; Non-Financial Interests, Personal, Member, WCLC annual congress Lung Cancer Track: WCLC; Non-Financial Interests, Personal, Member, Scientific Committee: IPOP (Italian lung cancer charity), TUTOR (Italian thymic malignancies charity); Non-Financial Interests, Personal, Member, Member since 2013–2018: EMA Scientific Advisory Group (SAG); Non-Financial Interests, Personal, Other, Scientific Programme Committee: AACR; Non-Financial Interests, Personal, Leadership Role, previous ESMO National Societies Committee Chair and ESMO Council Member: ESMO; Other, Personal, Other, Travel, Accommodations, Expenses: Pfizer; Other, Personal, Other, Relationships to Disclose Travel, Accommodations, Expenses: Roche, AstraZeneca; Other, Personal, Other, travel and accomodation: Merck. T. Mitsudomi: Financial Interests, Personal, Invited Speaker: AstraZeneca, Chugai, Novartis, MSD, Ono, Pfizer, Amgen, Takeda, Eli Lilly, Merck Biopharma, Bayer, Taiho, Daiichi Sankyo; Financial Interests, Personal, Advisory Board: AstraZeneca, Boehringer Ingelheim, Ono, Janssen, Regeneron, Bristol Myers Squibb; Financial Interests, Institutional, Research Grant: Bridge Bio; Non-Financial Interests, Personal, Principal Investigator, Co-Pi of the Aegean study: AstraZeneca; Non-Financial Interests, Personal, Principal Investigator, Co-Pi of the CheckMate 816 study: Bristol Myers Squibb; Non-Financial Interests, Personal, Leadership Role, immediate Past President 2021–2023, President 2019–2021: International Association for Study of Lung Cancer; Non-Financial Interests, Personal, Leadership Role, President (2014–2018): Japan Lung Cancer Society. 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, 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. K.M. Kerr: Financial Interests, Personal, Advisory Board, Consultancy: AbbVie, Amgen, AstraZeneca, Bayer, Debiopharm, Diaceutics, Merck Serono, Merck Sharp & Dohme, Novartis, Pfizer, Regeneron, Roche, Roche Diagnostics/Ventana, Janssen; Financial Interests, Personal, Invited Speaker: AstraZeneca, Amgen, Boehringer Ingelheim, Bristol-Myers Squibb, Eli Lilly, Merck Serono, Merck Sharp & Dohme, Novartis, Pfizer, Roche, Roche Diagnostics/Ventana, Medscape, Prime Oncology; Financial Interests, Personal, Advisory Board: Sanofi; Non-Financial Interests, Personal, Leadership Role, Past Pathology Committee Chair: IASLC; Non-Financial Interests, Personal, Member, Lobbying and pressure group for UK - generally writing reports to lobby government.: UK Lung Cancer Consortium. S. Peters: Financial Interests, Institutional, Advisory Board: Vaccibody, Takeda, Seattle Genetics, Sanofi, Roche/Genentech, Regeneron, Phosplatin Therapeutics, PharmaMar, Pfizer, Novartis, Mirati, Merck Serono, MSD, Janssen, Incyte, Illumina, IQVIA, GSK, Gilead, Genzyme, Foundation Medicine, F-Star, Eli Lilly, Debiopharm, Daiichi Sankyo, Boehringer Ingelheim, Blueprint Medicines, Biocartis, Bio Invent, BeiGene, Bayer, BMS, AstraZeneca, Arcus, Amgen, AbbVie, iTheos, Novocure; Financial Interests, Institutional, Invited Speaker: Takeda, Sanofi, Roche/Genentech, RTP, Pfizer, PRIME, PER, Novartis, Medscape, MSD, Imedex, Illumina, Fishawack, Eli Lilly, Ecancer, Boehringer Ingelheim, BMS, AstraZeneca, Oncology Education, RMEI, Mirati; Financial Interests, Personal, Other, Associate Editor Annals of Oncology and Deputy Editor Lung Cancer: Elsevier; Financial Interests, Institutional, Advisory Board, Permanent independent scientific advisor: Hutchmed; Financial Interests, Institutional, Member of Board of Directors, Swiss network of pharmacies: Galenica; Financial Interests, Institutional, Invited Speaker, MERMAID-1: AstraZeneca; Financial Interests, Institutional, Invited Speaker, MERMAID-2, POSEIDON, MYSTIC: AstraZeneca; Financial Interests, Institutional, Invited Speaker, Clinical Trial Steering committee CheckMate 743, CheckMate 73L, CheckMate 331 and 451: BMS; Financial Interests, Institutional, Invited Speaker, RELATIVITY 095: BMS; Financial Interests, Institutional, Invited Speaker, BGB-A317-A1217-301/AdvanTIG-301: BeiGene; Financial Interests, Institutional, Invited Speaker, Clinical Trial Chair ZEAL-1: GSK; Financial Interests, Institutional, Invited Speaker, Clinical Trial steering Committee PEARLS, MK-7684A: MSD; Financial Interests, Institutional, Invited Speaker, Clinical Trial Steering Committee SAPPHIRE: Mirati; Financial Interests, Institutional, Invited Speaker, LAGOON: PharmaMar; Financial Interests, Institutional, Invited Speaker, phase I/II trials: Phosplatin Therapeutics; Financial Interests, Institutional, Invited Speaker, Clinical Trial Chair Skyscraper-01; chair ALEX; steering committee BFAST; steering committee BEAT-Meso; steering committee ImPower-030, IMforte: Roche/Genentech; Financial Interests, Institutional, Invited Speaker, Phase 2 Inupadenant with chemo: iTeos; Non-Financial Interests, Personal, Officer, ESMO President 2020–2022: ESMO; Non-Financial Interests, Personal, Officer, Council Member & Scientific Committee Chair: ETOP/IBCSG Partners; Non-Financial Interests, Personal, Officer, Vice-President Lung Group: SAKK; Non-Financial Interests, Personal, Other, Involved in Swiss politics: Swiss Political Activities; Non-Financial Interests, Personal, Officer, President and Council Member: Ballet Béjart Lausanne Foundation; Non-Financial Interests, Personal, Principal Investigator, Involved in academic trials: ETOP/EORTC/SAKK; Non-Financial Interests, Personal, Member: Association of Swiss Physicians FMH (CH), ASCO, AACR, IASLC; Non-Financial Interests, Personal, Leadership Role, ESMO President: ESMO; Non-Financial Interests, Personal, Member, Vice-President Lung Group: SAKK; Non-Financial Interests, Personal, Leadership Role, Vice -President: SAMO; Non-Financial Interests, Personal, Member, Association of Swiss interns and residents: ASMAC/VSAO. D. Planchard: Financial Interests, Personal, Advisory Board: AstraZeneca, BMS, Merck, Novartis, Pfizer, Roche, Samsung, Celgene, AbbVie, Daiichi Sankyo, Janssen, Seagen, Gilead, Pierre Fabre; Financial Interests, Personal, Invited Speaker: AstraZeneca, Novartis, Pfizer, priME Oncology, Peer CME, Samsung, AbbVie, Janssen, Gilead, Seagen; Non-Financial Interests, Personal, Principal Investigator, Institutional financial interests: AstraZeneca, BMS, Merck, Novartis, Pfizer, Roche, Daiichi Sankyo, Sanofi-Aventis, Pierre Fabre, AbbVie, Sanofi, Janssen. S. Michiels: Financial Interests, Personal, Other, DSMB member: Servier, Biophytis, Yuhan, IQVIA, Kedrion; Financial Interests, Personal, Advisory Board, Study Scientific Committee member: Roche. All other authors have declared no conflicts of interest.