Abstract 35P
Background
SUNLIGHT, an international, open-label, randomized, phase 3 study comparing trifluridine/tipiracil (FTD/TPI) + bevacizumab (bev) to FTD/TPI monotherapy in patients (pts) with refractory metastatic colorectal cancer (mCRC), demonstrated a 3.3-month increase in overall survival (OS) with FTD/TPI + bev (HR: 0.61; 95% CI: 0.49–0.77; p<0.001). This analysis evaluated efficacy outcomes in pts with or without severe (grade ≥3) neutropenia (NEU) and/or neutrophil count decreased (NCD) (collectively referred as NEU/NCD).
Methods
In SUNLIGHT, pts with mCRC who had received two prior treatment regimens were randomized to FTD/TPI + bev or FTD/TPI. A post-hoc analysis was performed to evaluate OS and progression free survival (PFS) in two groups of pts: those with grade ≥3 NEU/NCD during the treatment period, and those with grade <3 NEU/NCD or without any.
Results
For pts with grade ≥3 NEU/NCD, those treated with FTD/TPI + bev had better OS (HR: 0.58; 95% CI: 0.40-0.85; p=0.0046) and better PFS (HR: 0.35; 95% CI: 0.25-0.49, p<0.0001) compared to pts treated with FTD/TPI. For pts with grade <3 NEU/NCD or without any, those treated with FTD/TPI + bev had better OS (HR: 0.71; 95% CI: 0.54-0.94, p=0.00176) and better PFS (HR: 0.54; 95% CI: 0.42-0.70: p<0.0001) compared to pts treated with FTD/TPI. For pts treated with FTD/TPI + bev, those with grade ≥3 NEU/NCD had better OS (HR: 0.37; 95% CI: 0.26-0.52; p<0.0001) and better PFS (HR: 0.41; 95% CI: 0.31-0.55; p<0.0001) compared to pts with grade <3 NEU/NCD or without any. For pts treated with FTD/TPI, those with grade ≥3 NEU/NCD had better OS (HR: 0.45; 95% CI: 0.32-0.63; p<0.0001) and better PFS (HR: 0.48; 95% CI: 0.35-0.64; p<0.0001) compared to pts with grade <3 NEU/NCD or without any. Table: 35P
| NEU and NCD were reported as follows: | ||
| FTD/TPI + bev n (%) | FTD/TPI n (%) | |
| NEU any grade | 62.2 | 51.2 |
| NEU grade ≥3 | 43.1 | 32.1 |
| NCD any grade | 13.8 | 6.9 |
| NCD grade ≥3 | 8.9 | 5.3 |
Conclusions
mCRC patients treated with FTD/TPI + bev had better OS and PFS than those treated with FTD/TPI, regardless of whether they experienced NEU/NCD grade ≥3 or not. Those who developed NEU/NCD grade ≥3 had better efficacy outcomes in both treatment arms.
Clinical trial identification
NCT04737187.
Legal entity responsible for the study
Taiho & Servier.
Funding
Taiho & Servier.
Disclosure
G. Prager: Financial Interests, Personal, Advisory Board: Merck, Amgen, Servier, Bayer, Pierre Fabre, CECOG, Daiichi Sankyo Austria, AstraZeneca; Financial Interests, Personal, Invited Speaker: Roche, Sanofi, Lilly, BMS, MSD, Incyte; Financial Interests, Personal, Advisory Board, Advisory: Takeda; Financial Interests, Institutional, Invited Speaker: Incyte, Servier, BMS, Novartis. J. Tabernero: Financial Interests, Personal, Advisory Board, scientific consultancy role: Orion Biotechnology, AstraZeneca, Boehringer Ingelheim, Chugai, Daiichi Sankyo, F. Hoffmann-La Roche Ltd., Genentech Inc., Ikena Oncology, Lilly, Menarini, Merck Serono, Merus, MSD, Mirati, Neophore, Novartis, Peptomyc, Pfizer, Pierre Fabre, Samsung Bioepis, Sanofi, Seattle Genetics, Servier, Taiho, Scandion Oncology, Ona Therapeutics, Sotio Biotech, Inspirna Inc, Scorpion Therapeutics, Tolremo Therapeutics, CARSgen Therapeutics, hC Bioscience Inc, Takeda Pharmaceuticals International AG, Alentis Therapeutics, Immodulon Therapeutics; Financial Interests, Personal, Invited Speaker, educational collaboration: Medscape Education, Physicians Education Resource (PER), PeerView Institute for Medical Education, Imedex/HMP; Financial Interests, Personal, Advisory Board: Cardiff Oncology, Aveo Oncology; Financial Interests, Personal, Stocks/Shares: Oniria Therapeutics, 1TRIALSP, Alentis Therapeutics, Pangaea Oncology; Financial Interests, Institutional, Research Grant, ACRCelerate: Colorectal Cancer Stratified: Fundación Científica de la Asociación Española Contra el Cáncer; Financial Interests, Institutional, Research Grant, OPTIMISTICC: Opportunity to Investigate the Microbiome’s Impact on Science and Treatment In Colorectal Cancer: Cancer Research UK; Financial Interests, Institutional, Funding, Clinical Trials & Research: Amgen Inc, AstraZeneca Pharmaceuticals LP, Bristol Myers Squibb International Corporation, Celgene International SARL, Debiopharm International SA, F. Hoffmann-La Roche Ltd., Genentech Inc, Janssen-Cilag International NV, Merck Health KGaA, Merck, Sharp & Dohme de España, SA, Novartis Farmacéutica SA, PharmaMar SA, Sanofi-Aventis Recherche & Développement, Servier, Taiho Pharma USA, Inc, BeiGene, Boehringer Ingelheim, Menarini, Merus N V, Pfizer, Mirati; Non-Financial Interests, Member of Board of Directors, Board of Directors: Cancer Core Europe, Spanish Association Against Cancer -AECC; Non-Financial Interests, Member of Board of Directors, General Assembly: Horizon Europe Cancer Mission; Non-Financial Interests, Leadership Role, External Scientific Committee: Institute for Health Research INCLIVA – Clinical Hospital of Valencia, IdiSNA –Universidad de Navarra; Non-Financial Interests, Leadership Role, Scientific Advisory Board: Spanish National Cancer Research Centre (CNIO); Non-Financial Interests, Advisory Role, International Scientific Evaluation Committee: Bosch Health Campus (BHC); Non-Financial Interests, Advisory Role, Review Board: National Decade Against Cancer (NCT) - German Consortium for Translational Cancer Research (DKTK); Non-Financial Interests, Advisory Role, Scientific Advisory Board: Karolinska Comprehensive Cancer Centre; Non-Financial Interests, Advisory Role, International Review Committee (IRC): Oncode Institute; Non-Financial Interests, Advisory Role, Scientific Advisory Board (SAB): Oslo University Hospital Comprehensive Cancer Centre (OUH CCC); Non-Financial Interests, Leadership Role, Governance Advisory Committee: European Organization for Research and Treatment of Cancer -EORTC; Non-Financial Interests, Leadership Role, Vice Chairman: World Innovative Networking (WIN) Consortium in Personalized Cancer Medicine; Non-Financial Interests, Other, Coordinating PI & Steering Committee Member. Clinical Trials & Research: Array Biopharma Inc., AstraZeneca Pharmaceutical LP, Boehringer Ingelheim, MedImmune, Menarini, Merck Healthcare KGaA, Merck, Sharp & Dohme de España SA, Pfizer, Servier; Non-Financial Interests, Principal Investigator, Clinical Trials & Research: Array Biopharma Inc., AstraZeneca Pharmaceutics LP, BeiGene, Boehringer Ingelheim, Bristol Myers Squibb International Corporation, Celgene International SARL, Debiopharm International SA, F. Hoffmann-La Roche Ltd., Genentech Inc., HalioDX SAS, Hutchinson Medipharma, Janssen-Cilag International NV, MedImmune, Menarini, Merck Healthcare KGaA, Merck, Sharp & Dohme de España SA, Merus NV, Mirati, Novartis Farmacéutica SA, Pfizer, Sanofi-Aventis Recherche & Développement, Servier, Taiho Pharma USA Inc; Non-Financial Interests, Other, Steering Committee Member. Clinical Trials & Research: Debiopharm International SA, F. Hoffmann-La Roche Ltd., Genentech Inc., HalioDX SAS, Hutchinson Medipharma, Janssen-Cilag International NV, Merus NV, Taiho Pharma USA Inc; Non-Financial Interests, Other, Coordinating PI. Clinical Trials & Research: Mirati; Non-Financial Interests, Member: AACR, ASCO, EACR, EORTC, SEOM; Other, President: Oncology Master Plan – Catalonia Department of Health; Other, Advisory Committee: Advisory Committee on Pharmaceutical Provision Financing under the Spanish National Health System. M. Fakih: Financial Interests, Personal, Advisory Board, Consultant: AstraZeneca, Bayer Corporation, AbbVie, Inc.; Financial Interests, Personal, Advisory Board, Consultant/One Meeting: Bristol Myers Squibb; Financial Interests, Personal, Advisory Board, One meeting: Eisai Oncology; Financial Interests, Personal, Advisory Board, One meeting: Entos, Seattle Genetics, Xenthera; Financial Interests, Personal, Advisory Board: Merck, Nouscom, Roche/Genentech; Financial Interests, Personal, Advisory Board, Also Editorial Boards & Consulting: Mirati Therapeutics; Financial Interests, Personal, Advisory Board, Consulting/One Meeting: Pfizer; Financial Interests, Personal, Advisory Board, Consulting: Taiho Oncology; Financial Interests, Personal, Advisory Board, One Meeting: Janssen; Financial Interests, Institutional, Research Grant: AgenusBio, Genentech/imCORE, Verastem. F. Ciardiello: Financial Interests, Personal, Advisory Board: Roche, Merck Serono, Servier, Pierre Fabre, Pfizer; Financial Interests, Institutional, Research Grant: Merck Serono, Roche, Amgen; Financial Interests, Institutional, Invited Speaker: Pfizer, Pierre Fabre, Servier. E. Van Cutsem: Financial Interests, Personal, Advisory Board: AbbVie, Agenus, ALX, Arcus Biosciences, Astellas, AstraZeneca, Bayer, BeiGene, BioNTech, Boehringer Ingelheim, Bristol Myers Squibb, Daiichi Sankyo, Debiopharm, Elmedix, Eisai, GSK, Hoopika Biotech, Incyte, Ipsen, Lilly, Merck Sharp & Dohme, Merck KGaA, Mirati, Novartis, Nordic, Pierre Fabre, Seattle Genetics, Servier, Simcere, Takeda, Taiho, Terumo; Financial Interests, Personal, Invited Speaker: Amgen, Pfizer. L. Roby: Financial Interests, Personal, Full or part-time Employment: Institut de Recherches Internationales Servier. W. Yao: Financial Interests, Personal, Full or part-time Employment: Servier Pharmaceuticals. E. Choucair: Financial Interests, Personal, Full or part-time Employment: Servier. J. Taieb: Financial Interests, Personal, Advisory Board: MSD, Merck, Servier, Pierre Fabre, Amgen, BMS, Novartis, Pfizer, Sanofi, Rottapharm, Takeda; Financial Interests, Personal, Expert Testimony: Astellas, Takeda; Financial Interests, Personal, Invited Speaker: Amgen, BMS, Merck, MSD, Novartis; Financial Interests, Personal, Invited Speaker, symposia: Astellas; Financial Interests, Personal, Other, steering committee of clinical trial: Novartis; Non-Financial Interests, Leadership Role, President of the scientific committee of the ARCAD foundation until end 2022: ARCAD Foundation; Non-Financial Interests, Leadership Role, Chair of the ARCAD pancreas research group: ARCAD Foundation; Non-Financial Interests, Leadership Role, Member of the administrative council, the scientific committee, the executive board and responsible for the international relationships /partnership for FFCD in the prodige intergroup: Federation Francophone de Cancerologie Digestive (FFCD); Non-Financial Interests, Other, steering committee of clinical trials: Pfizer, Servier.