526P - Efficacy and safety of fruquintinib in refractory metastatic colorectal cancer: A FRESCO-2 subgroup analysis by age

Background

The median age of colorectal cancer (CRC) diagnosis in the US is 66 yrs, but incidence among adults aged <50 yrs is increasing. Fruquintinib (F) is a highly selective, oral inhibitor of all 3 VEGF receptors (-1, -2, and -3). Both the phase 3 FRESCO (NCT02314819) and FRESCO-2 (NCT04322539) studies met their primary endpoints, demonstrating significantly improved overall survival (OS) with F + best supportive care (BSC) vs placebo (P) + BSC (FRESCO: median 9.3 vs 6.6 months [mos]; HR 0.65; FRESCO-2: median 7.4 vs 4.8 mos; HR 0.66). We present results of a FRESCO-2 subgroup analysis by age.

Methods

Patient (pts) were randomized 2:1 to F + BSC vs P + BSC. Primary endpoint was OS; secondary endpoints included PFS and safety. This analysis evaluated data in pts aged <55, 55−64, 65−74, and ≥75 yrs.

Results

For F + BSC (n=461) vs P + BSC (n=230), 103 vs 44 pts were aged <55; 144 vs 75 were aged 55−64; 170 vs 96 were aged 65−74; 44 vs 15 were aged ≥75 yrs. Key baseline characteristics are shown in the Table. Median OS was longer with F vs P in all age groups: pts aged <55 yrs (6.6 vs 4.5 mos; HR 0.73; 95% CI 0.48−1.10), 55−64 yrs (7.9 vs 5.3 mos; HR 0.68; 95% CI 0.47−0.96), 65−74 yrs (7.6 vs 4.4 mos; HR 0.67; 95% CI 0.50−0.91), and ≥75 yrs (7.0 vs 5.4 mos; HR 0.56; 95% CI 0.26−1.21). Median PFS was also improved with F vs P in each age subgroup: 3.0 vs 1.8 mos (HR 0.45; 95% CI 0.30−0.67); 3.8 vs 1.9 mos (HR 0.22; 95% CI 0.15−0.32); 3.7 vs 1.8 mos (HR 0.32; 95% CI 0.24−0.43); 3.7 vs 1.9 mos (HR 0.20; 95% CI 0.09−0.44). Safety outcomes were similar across age subgroups (Table). The most common grade ≥3 treatment-emergent adverse event (TEAE) with F was hypertension for pts aged <55 (14%), 55−64 (15%), and 65−74 (12%), and palmar-plantar erythrodysesthesia for pts aged ≥75 yrs (16%).

Conclusions

Efficacy and safety of F were consistent with the overall FRESCO-2 cohort including in young onset and elderly pts. F provides an effective and tolerable treatment option for pts with previously treated mCRC, irrespective of age. Table: 526P

Baseline characteristics (ITT population) and TEAEs (safety population)

*Pt was randomized to F but received P. Note: 3 vs 2 pts randomized to F vs P did not receive treatment.

Clinical trial identification

NCT04322539, 2020-03-26.

Editorial acknowledgement

Medical writing support for the development of this poster, under the direction of the authors, was provided by Christian Jones, PhD, of Ashfield MedComms, an Inizio Company, funded by Takeda Pharmaceuticals U.S.A., Inc., Lexington, MA.

Legal entity responsible for the study

Hutchmed.

Funding

Hutchmed.

Disclosure

M.E. Elez Fernandez: Financial Interests, Personal, Advisory Board: Hoffman La - Roche, Servier, Amgen, Merck Serono, Sanofi, Bayer, Pierre Fabre, MSD, Takeda, Boehringer Ingelheim, Cure Teq AG, Repare Therapeutics Inc., RIN Institute Inc., Janssen; Financial Interests, Personal, Invited Speaker: Organon, Novartis, Pfizer, BMS, Lilly, Medscape; 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, Abbvie Deutschland Gmbh & Co KG, Bayer Pharma AG, Bioncotech Therapeutics, S.L., Biontech Rna Pharmacuticals GMBH, Biontech Small Molecules GMBH, Boehringer Ingelheim de España S.A., Daiichi Sankyo, Inc, Gercor, Hutchinson Medipharma Limited, Iovance Biotherapeutics, Inc., Janssen Research & Development, Menarini Ricerche SPA, Merck, Sharp & Dohme De España S.A., Nouscom SRL., Pledpharma AB, Redx Pharma PLC, Scandion Oncology, Seattle Genetics Inc., Sotio A.S., Wntresearch AB; 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); Non-Financial Interests, Leadership Role, Member of the Scientific Program Committee and Developmental Therapeutics-Immunotherapy Track Leader, 2023-2024 term: American Society for Clinical Oncology (ASCO); Non-Financial Interests, Other, Member of the Scientific Committee 2024: European Society for Medical Oncology (ESMO); Other, Travel, Accommodations, Expenses: Roche, Merck Serono, Sanofi, Amgen, Array BioPharma, Servier, Bristol-Myers Squibb. N..A. Dasari: Financial Interests, Personal, Advisory Board: HutchMed, AAA, Personalis, Illumina, Takeda; Financial Interests, Institutional, Trial Chair: HutchMed, Eisai, Guardant Health, Natera, Xencor, Taiho; Financial Interests, Institutional, Coordinating PI: Enterome. S. Lonardi: Financial Interests, Personal, Advisory Board: Amgen, merck serono, lilly, Servier, AstraZeneca, MSD, Incyte, Daiichi-Sankyo, Bristol-Myers Squibb, Astellas, GSK, Takeda, Bayer, Rottapharm; Financial Interests, Personal, Invited Speaker: Pierre-Fabre, GSK, Roche, Servier, Amgen, Bristol-Myers Squibb, Incyte, Lilly, Merck Serono, MSD, AstraZeneca; Financial Interests, Institutional, Coordinating PI: Amgen, Merck Serono, Bayer, Roche, Lilly, AstraZeneca, Bristol -Myers Squibb; Non-Financial Interests, Member of Board of Directors, Italian No-Profit Oncology Research Foundation supporting academic Clinical trials: GONO Foundation. C. Eng: Financial Interests, Personal, Advisory Board: Abbvie, amgen, California Institute of Regenerative Medicine, Hoopika, Janssen, merck, Taiho, takeda, Seagen; Financial Interests, Institutional, Local PI: Janssen, Gritstone, Pfizer, Merck, Sumitomo, Agenus; Financial Interests, Institutional, Research Grant: Haystack, Natera; Financial Interests, Institutional, Coordinating PI: Hutchinson. R. 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Yoshino: Financial Interests, Personal, Invited Speaker: Chugai Pharmaceutical Co., Ltd., Merck Biopharma Co., Ltd., Bayer Yakuhin, Ltd., Ono Pharmaceutical Co., Ltd., MSD K.K., Takeda Pharmaceutical Co., Ltd.; Financial Interests, Personal, Other, Consultancy: Sumitomo Corp.; Financial Interests, Institutional, Research Grant: Ono Pharmaceutical Co., Ltd, Sanofi K.K., MSD K.K., Taiho Pharmaceutical Co., Ltd., Molecular Health GmbH, Amgen K.K., Pfizer Japan Inc., Genomedia Inc., Sysmex Corp., Daiichi Sankyo Co., Ltd., Chugai Pharmaceutical Co., Ltd., Nippon Boehringer Ingelheim Co., Ltd., Eisai Co., Ltd., Roche Diagnostics K.K., FALCO Biosystems Ltd., Merus N.V., Bristol-Myers Squibb K.K., Medical & Biological Laboratories Co., LTD., Takeda Pharmaceutical Co., Ltd. A. Sobrero: Financial Interests, Personal, Invited Speaker: Servier, Bayer, Amgen, Pierre Fabre; Financial Interests, Personal, Advisory Board: BMS, MSD, Hutchmed, Astellas; Financial Interests, Personal, Stocks/Shares: Amgen. J.C. Yao: Financial Interests, Personal, Advisory Board: Ipsen, Exelixis, Amgen; Financial Interests, Personal, Other, Consultancy: HutchMed, Crinetics, Acrotech Biopharma; Financial Interests, Institutional, Local PI: Advanced Accelerator Applications International; Non-Financial Interests, Advisory Role, Adult Oncology Steering Board Membership: Epic. P. García Alfonso: Financial Interests, Personal, Advisory Board: Amgen. A. Sartore Bianchi: Financial Interests, Personal, Advisory Board: Amgen, Servier, Novartis; Financial Interests, Personal, Invited Speaker: Bayer, Guardant Health, Pierre Fabre. T. Satoh: Financial Interests, Personal, Invited Speaker, invited speaker and advisory: Ono Pharmaceutical, Daiichi Sankyo; Financial Interests, Personal, Invited Speaker, Invited speaker and advisory: Bristol Myers Squibb; Financial Interests, Personal, Invited Speaker, Invited speaker and advisory: Elli-Lilly, Yakult-Honsha; Financial Interests, Personal, Invited Speaker: Chugai Pharmazeutical, Merck-Biopharm, Takeda, Taiho; Financial Interests, Personal, Advisory Board: Takara-Bio; Financial Interests, Institutional, Local PI, Research Grant: Merck-Biopharm, Ono Pharmaceutical, Chugai Pharmaceutical, Yakult Honsha, Bristol-Myers, Elli-Lilly, Daiichi-Sankyo, Parexel, Taiho, Amgen, Phizer. V. Randrian: Financial Interests, Speaker, Consultant, Advisor: Takeda, Merck, Amgen; Financial Interests, Other, Invitation to conference: Takeda; Financial Interests, Advisory Board, Invitation to conference: Amgen; Financial Interests, Institutional, Research Funding: Servier. C. Cremolini: Financial Interests, Personal, Advisory Board: Roche, MSD, Amgen, Pierre Fabre, Nordic Pharma, Takeda; Financial Interests, Personal, Invited Speaker: Bayer, Servier, Merck Serono; Financial Interests, Institutional, Coordinating PI: Roche, Bayer, Servier, Merck; Financial Interests, Institutional, Local PI: Seagen, Hutchinson. Z. Yang: Financial Interests, Full or part-time Employment: Hutchmed; Financial Interests, Stocks or ownership: Hutchmed. W. Schelman: Financial Interests, Full or part-time Employment: Hutchmed; Financial Interests, Stocks or ownership: Hutchmed. H. Zhu: Financial Interests, Full or part-time Employment: Takeda; Financial Interests, Stocks or ownership: Takeda. L. Chen: Financial Interests, Stocks or ownership: Takeda. J. Tabernero: Financial Interests, Personal, Advisory Board, Scientific Consultancy role: Orion Biotechnology, AstraZeneca, Boehringer Ingelheim, Chugai, Daichii 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 Therapeuics, 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. All other authors have declared no conflicts of interest.