520P - Efficacy and safety of fruquintinib in patients with refractory metastatic colorectal cancer with and without liver metastasis: A subgroup analysis of the phase III FRESCO-2 trial

Background

The liver is the most common site of metastasis for colorectal cancer (CRC); approximately 50% of patients (pts) with CRC will develop liver metastases (mets) and these pts have worse outcomes compared to pts without liver mets. Fruquintinib (F) is a highly selective, oral inhibitor of all 3 VEGFRs (-1, -2, and -3) and was approved by the US FDA for previously treated metastatic CRC (mCRC), irrespective of biomarker status. Approval was based on the FRESCO (NCT02314819) and FRESCO-2 (NCT04322539) studies, which met their primary endpoints demonstrating consistent improvements in overall survival (OS) with F vs placebo (P) in pts with mCRC.

Methods

In FRESCO-2, pts were randomized 2:1 to F + best supportive care (BSC) vs P + BSC. Primary endpoint was OS; secondary endpoints included progression-free survival (PFS), disease control rate (DCR), and safety. This analysis evaluated efficacy and safety, focusing on hepatic function abnormality, according to the presence and absence of liver mets at baseline.

Results

339/461 (74%) and 156/230 (68%) pts randomized to receive F and P had liver mets, respectively. OS was improved with F vs P in pts with liver mets (median 6.4 vs 3.7 months [mos]; HR 0.58; 95% CI 0.47−0.71), and without liver mets (median 12.1 vs 8.4 mos; HR 0.77; 95% CI 0.51−1.16). PFS was also improved with F vs P in pts with and without liver mets: median 3.6 vs 1.8 mos (HR 0.29; 95% CI 0.23−0.36) and 4.5 vs 1.9 mos (HR 0.33; 95% CI 0.24−0.48), respectively. DCR was higher with F vs P in pts with liver mets (53 vs 8%) and without (64 vs 32%). Rates of any grade and grade ≥3 treatment emergent adverse events with F vs P were 99 vs 94% and 64 vs 54% in pts with liver mets, and 99 vs 91% and 60 vs 44% in pts without liver mets. Rates of any grade and grade ≥3 hepatic function abnormalities, per adverse event of special interest category, were comparable with F vs P in pts with liver mets (28 vs 26%; 10 vs 13%) but higher with F vs P in pts without liver mets (16 vs 4%; 3 vs 1%).

Conclusions

These data demonstrate that F consistently improved OS vs P in pts with previously treated mCRC with and without liver mets at baseline. F is an effective and tolerable treatment option for pts with mCRC regardless of liver mets.

Clinical trial identification

NCT04322539, 2020-03-26.

Editorial acknowledgement

Medical writing support, under the direction of the authors, was provided by Helen Wilkinson, 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

R. Garcia-Carbonero: Financial Interests, Personal, Advisory Board: AAA, Advanz Pharma, Amgen, Astellas, Bayer, BMS, Boehringer Ingelheim, Esteve, Hutchmed, Ipsen, Midatech Pharma, MSD, Novartis, PharmaMar, Servier, Takeda; Financial Interests, Institutional, Research Grant: BMS, MSD, Pfizer; Non-Financial Interests, Leadership Role, Global PI of investigator-initiated clinical trials (AXINET, NICENEC, PEMBROLA): BMS, MSD, Pfizer; Non-Financial Interests, Leadership Role, Chair Elect: European Neuroendocrine Tumor Society (ENETS); Non-Financial Interests, Leadership Role, Past President, Member of the Executive Committee: Grupo Español de Tumores Neuroendocrinos (GETNE); Other, Honoraria received by spouse for Advisory Board or invited speaker roles: AbbVie, AstraZeneca, Bayer, Boehringer Ingelheim, BMS, Genomica, Lilly, MSD, Merck, Novartis, Pfizer, PharmaMar, Roche, Sanofi, Servier, Takeda. N..A. Dasari: Financial Interests, Personal, Advisory Board: HutchMed, Exelixis, Personalis, Illumina, Takeda; Financial Interests, Institutional, Trial Chair: HutchMed, Eisai, Guardant Health, Natera, Xencor, Taiho; Financial Interests, Institutional, Coordinating PI: Enterome. 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. 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. T. 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.. H. Hochster: Financial Interests, Advisory Role: Merck, Processa Pharmaceuticals; Financial Interests, Stocks or ownership: Processa Pharmaceuticals, Compass Therapeutics; Financial Interests, Other: Seagen. D. Arnold: Financial Interests, Personal, Invited Speaker: AstraZeneca, Sanofi (Genzyme), Boston Scientific, Amgen, Merck (Serono), Servier, Ipsen, Boehringer Ingelheim, Eisai, GSK, Viatris, Amgen, Sirtex, PeerMD (China); Financial Interests, Personal, Advisory Board: Bristol Myers Squibb, Pierre Fabre Pharma, Boston Scientific, AstraZeneca, Gilead, Janssen Cilag; Financial Interests, Personal, Advisory Board, Advisory Board participations and Invited Speaker roles: Merck Sharp & Dohme; Financial Interests, Personal, Advisory Board, Advisory Board participation and Invited Speaker role: Terumo, Seagen, Amgen, Takeda; Financial Interests, Personal, Invited Speaker, CME Provider: PRMA Consulting, Tactics MD LLC, WebMD Health Corp, From Research to Practice, Aptitude Health, Art Tempi Media, Imedex, Streamitup Germany, Clinical Care Options (CCO), MCI, IOMEDICO (Germany); Financial Interests, Personal, Advisory Board, Consulting Agency: CRA International; Financial Interests, Personal, Advisory Board, CME Provider, App Producer: Onkowissen; Financial Interests, Personal, Other, Roles as Assoc. Editor for ESMO Open and Annals of Oncology: Elsevier; Financial Interests, Personal, Other, Role as Associate Editor Clin Colorect Cancer: Elsevier; Financial Interests, Institutional, Other, DSMB chair: Sanofi (Genzyme); Financial Interests, Institutional, Coordinating PI: OncoLytics; Financial Interests, Institutional, Funding, Educational Grant: AbbVie; Non-Financial Interests, Project Lead, non-compensated Scientific Advisory Board member: OncoLytics; Non-Financial Interests, Advisory Role, non-compensated Scientific Advisory Board member: Phanes Therapeutics Inc.; Non-Financial Interests, Leadership Role, GI Group Steering Committee: EORTC; Non-Financial Interests, Leadership Role, Steering Committee Member: AIO (German Cancer Society); Non-Financial Interests, Member: ASCO, ESO, DGHO. V. Randrian: Financial Interests, Speaker, Consultant, Advisor: Takeda, Merck, Amgen; Financial Interests, Other, Invitation to conference: Takeda, Amgen; Financial Interests, Institutional, Research Funding: Servier. W. Schelman: Financial Interests, Full or part-time Employment: Hutchmed; Financial Interests, Stocks or ownership: Hutchmed. L. Dong, Z. Yu, L. Chen: Financial Interests, Full or part-time Employment: Takeda. 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.