613P - Effect of prior use of anti-VEGF agents on overall survival in patients with refractory metastatic colorectal cancer: A post-hoc analysis of the phase III SUNLIGHT trial

Background

SUNLIGHT, an international, open-label, randomized, phase 3 study comparing trifluridine/tipiracil (FTD/TPI) + bevacizumab (FTD/TPI + bev) vs FTD/TPI monotherapy in patients (pts) with metastatic colorectal cancer (mCRC), demonstrated a 3.3-month increase in overall survival (OS) from 7.5 months with FTD/TPI monotherapy to 10.8 months with FTD/TPI + bev (HR, 0.61; 95% CI: 0.49 - 0.77; P<0.001). Here discussed are data on the effects of prior anti-VEGF use on OS.

Methods

A post-hoc analysis of SUNLIGHT was conducted in ptns with anti-VEGF treatment during prior regimens to assess the effect of prior anti-VEGF use on OS in a subgroup analysis and evaluate the treatment benefit associated with FTD/TPI + bev vs FTD/TPI monotherapy in each subgroup. Of note, the trial was not powered to detect statistical significance in this analysis.

Results

In the subgroup analysis (no anti-VEGF [group 1], anti-VEGF in first regimen only [group 2], anti-VEGF in second regimen only [group 3], and anti-VEGF in both first and second regimens [group 4]), ptns treated with FTD/TPI + bev had a higher OS than those treated with FTD/TPI monotherapy in each prespecified subgroup. In group 1, mOS was 16.36 months (95% CI: 11.86 - NA) with FTD/TPI + bev vs 7.39 months (95% CI: 5.52 - 9.3) with FTD/TPI monotherapy (HR, 0.42; 95% CI: 0.25 - 0.69). In group 2, mOS was 10.41 months (95% CI: 8.54 - 15.31) with FTD/TPI + bev vs 7.23 months (95% CI: 5.55 - 12.52) with FTD/TPI monotherapy (HR, 0.65; 95% CI: 0.38 - 1.1). In group 3, mOS was 9 months (95% CI: 8.15 - 15.14) with FTD/TPI + bev vs 8.15 months (95% CI: 6.21 - 10.18) with FTD/TPI monotherapy (HR, 0.66; 95% CI: 0.44 - 1). In group 4, mOS was 9.36 months (95% CI: 7.49 - 10.97) with FTD/TPI + bev vs 6.9 months (95% CI: 5.98 - 8.51) with FTD/TPI monotherapy (HR, 0.76; 95% CI: 0.52 - 1.1). In group 2, the OS was similar to the other subgroups, suggesting that an anti-VEGF break did not have any impact on the efficacy.

Conclusions

All subgroups showed a comparable OS benefit. The benefit of FTD/TPI + bev vs FTD/TPI on OS is observed independently of the use or not of anti-VEGF during prior regimens. For ptns who had prior anti-VEGF, this benefit is observed independently of whether they had anti-VEGF breaks or not.

Clinical trial identification

NCT04737187.

Editorial acknowledgement

Legal entity responsible for the study

Servier and Taiho Oncology, Inc.

Funding

Servier and Taiho Oncology, Inc.

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, Bristol Myers Squibb, MSD; Financial Interests, Institutional, Local PI: Incyte, Servier, Bristol Myers Squibb, Novartis. J. Taieb: Financial Interests, Personal, Advisory Board: MSD, Astellas, Merck, Servier, Pierre Fabre, Amgen, Bristol Myers Squibb, Novartis, Pfizer; Financial Interests, Personal, Invited Speaker: Amgen, Bristol Myers Squibb, Merck, MSD, 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). M. Fakih: Financial Interests, Personal, Advisory Role: Amgen, Taiho Pharmaceutical, Bayer, Pfizer, Seagen, GSK, Incyte, Nouscom, Roche/Genentech, Mirati Therapeutics, Bristol Myers Squibb, Eisai, Merck; Financial Interests, Personal, Speaker’s Bureau: Guardant Health; Financial Interests, Personal, Financially compensated role: Amgen; Financial Interests, Institutional, Funding: Amgen, 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, Local PI: Pfizer, Pierre Fabre, Servier. E. Van Cutsem: Financial Interests, Personal, Advisory Board: AbbVie, ALX, Amgen, Array, Astellas, AstraZeneca, Bayer, BeiGene, Boehringer Ingelheim, Bristol Myers Squibb, Daiichi Sankyo, GSK, Incyte, Ipsen, Lilly, Merck Sharp & Dohme, Merck KGaA, Mirati, Novartis, Nordic, Pierre Fabre, Pfizer, Roche, Seattle Genetics, Servier, Takeda, Terumo, Taiho, Zymeworks; Financial Interests, Institutional, Research Grant: Amgen, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Ipsen, Lilly, Merck Sharp & Dohme, Merck KGaA, Novartis, Roche, Servier. M.E. Elez Fernandez: Financial Interests, Personal, Advisory Board: Hoffman La - Roche, Servier, Amgen, Merck Serono, Sanofi, Bayer, Pierre Fabre, MSD; Financial Interests, Personal, Invited Speaker: Organon, Novartis; Financial Interests, Personal, Other, Educational training: Seagen International GmbH; Financial Interests, Institutional, Funding: Hoffmann-La Roche Ltd, Sanofi Aventis Recherche & Développement, Amgen Inc., Boehringer Ingelheim, Novartis Farmacéutica SA, Bristol Myers Squibb International Corporation, BeiGene, HalioDX SAS, Janssen-Cilag SA, Merck Health KGAA, Merck Sharp & Dohme de España SA, PharmaMar SA, Servier, Taiho Pharma USA Inc, Hutchison MediPharma International, Menarini, Merus NV, Pfizer, Mirati, Array Biopharma Inc, AstraZeneca Pharmaceuticals LP, Celgene International SARL, Debiopharm International SA, Genentech Inc, MedImmune; Non-Financial Interests, , Other, Coordinator of the SEOM +MIR Section of Residents and Young Assistants: Sociedad Española de Oncología Médica (SEOM); Non-Financial Interests, Other, Speaker of the ESMO Academy: European Society for Medical Oncology (ESMO); Non-Financial Interests, Other, Volunteer member of the ASCO Annual Meeting Scientific Program Committee: Developmental Therapeutics – Immunotherapy: American Society of Clinical Oncology (ASCO); Other, Travel, accommodations, expenses.: Roche, Merck Serono, Sanofi, Amgen, Array BioPharma, Servier, Bristol Myers Squibb. F.J.S.M. Cruz: Financial Interests, Personal, Advisory Role: Janssen Oncology, Novartis. L.S. Wyrwicz: Financial Interests, Personal, Advisory Board: Bristol Myers Squibb, Servier; Financial Interests, Personal and Institutional, Local PI: Bristol Myers Squibb, MSD, Servier, BeiGene, Roche, AstraZeneca; Financial Interests, Personal, Steering Committee Member: AstraZeneca. P.G. Poureau: Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Servier, Ipsen; Financial Interests, Personal, Financially compensated role: Merck, Pierre Fabre, Ipsen; Financial Interests, Personal, Funding: Servier. G. Liposits: Financial Interests, Personal, Other, Received funding for working in an expert panel.: Nutricia AS; Financial Interests, Personal, Invited Speaker, Workshop: Servier; Non-Financial Interests, , Member: International Society of Geriatric Oncology (SIOG). C. Cremolini: Financial Interests, Personal, Advisory Board: Roche, MSD, Amgen, Pierre Fabre, Nordic Pharma; Financial Interests, Personal, Invited Speaker: Bayer, Servier, Merck Serono; Financial Interests, Institutional, Coordinating PI: Roche, Bayer, Servier, Merck. D.P. Modest: Financial Interests, Personal, Invited Speaker: Amgen, Servier, Merck, Onkowissen, MSD, Bristol Myers Squibb, AstraZeneca, Pierre Fabre, Lilly, Cureteq, GSK, Seagen, Medison, COR2ED, JE, 21up; Financial Interests, Personal, Advisory Board: Amgen, Servier, Merck, MSD, Bristol Myers Squibb, Incyte, Takeda, G1, Onkowissen, PierreFabre, AstraZeneca; Financial Interests, Institutional, Research Grant: Amgen; Financial Interests, Institutional, Coordinating PI: Servier. E.M. Calleja: Financial Interests, Personal, Full or part-time Employment: Taiho Oncology Inc. L. Roby: Financial Interests, Personal, Full or part-time Employment: Servier. V. Barboux: Financial Interests, Personal, Full or part-time Employment: Servier. N. Causse-Amellal: Financial Interests, Personal, Full or part-time Employment: Servier. J. Tabernero: Financial Interests, Personal, Advisory Board, scientific consultancy role: Orion Biotechnology, Array Biopharma, AstraZeneca, Bayer, Boehringer Ingelheim, Chugai, Daiichi Sankyo, F. Hoffmann-La Roche Ltd, Genentech Inc., HalioDX SAS, Ikena Oncology, IQVIA, Lilly, Menarini, Merck Serono, Merus, MSD, Mirati, Neophore, Novartis, Peptomyc, Pfizer, Pierre Fabre, Samsung Bioepis, Sanofi, Seattle Genetics, Servier, Taiho, Tessa Therapeutics, TheraMyc, Hutchinson MediPharma International, Scandion Oncology, Ona Therapeutics, Sotio Biotech, Inspirna Inc, Scorpion Therapeutics, Tolremo Therapeutics; Financial Interests, Personal, Invited Speaker, educational collaboration: Medscape Education, Physicians Education Resource (PER), PeerView Institute for Medical Education, Imedex / HMP; Financial Interests, Personal, Invited Speaker, educacional collaboration: MJH Life Sciences; Financial Interests, Personal, Advisory Board: Cardiff Oncology; Financial Interests, Personal, Stocks/Shares: Oniria Therapeuics; 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, Array Biopharma 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, HalioDX SAS, Hutchinson Medipharma, MedImmune, 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, Principal Investigator, Clinical Trials & Research: AstraZeneca Pharmaceutics LP, Array Biopharma Inc., BeiGene, Boehringer Ingelheim, Debiopharm International SA, Bristol Myers Squibb International Corporation, Celgene International SARL, F. Hoffmann-La Roche Ltd, Genentech Inc., HalioDX SAS, Hutchinson Medipharma, Menarini, Janssen-Cilag International NV, MedImmune, 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, 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, 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. All other authors have declared no conflicts of interest.