Abstract 31P
Background
In the global, randomized, double-blind, phase 3 FRESCO-2 trial (NCT04322539), fruquintinib (F) + best supportive care (BSC) demonstrated significantly improved overall survival (OS) vs placebo (P) + BSC with a manageable safety profile in patients (pts) with refractory metastatic colorectal cancer (mCRC). This analysis investigated the impact of the number of metastatic sites and the time from metastasis diagnosis to randomization on outcomes.
Methods
In this exploratory post-hoc analysis, pts were grouped according to good prognostic characteristics (GPC; single metastatic site [suggestive of low tumor burden], >18 months from diagnosis of metastasis to randomization [suggestive of indolent disease]) or poor prognostic characteristics (PPC; all remaining pts). Efficacy and safety were assessed according to prognostic subgroups and treatment.
Results
Overall in FRESCO-2, regardless of treatment randomization, 91 pts were included in the GPC subgroup and the remaining 600 in the PPC subgroup. In the GPC subgroup, median OS was 10.2 months vs 6.3 months in the PPC subgroup (p<0.001). F resulted in improvements in OS vs P in the GPC subgroup (median 11.0 vs 6.3 months; hazard ratio [HR] 0.474, 95% confidence interval [CI] 0.243, 0.923; p=0.0134) and in the PPC subgroup (median 7.1 vs 4.3 months; HR 0.633, 95% CI 0.519, 0.773; p<0.0001). PFS and time to deterioration to ECOG PS ≥2 were also improved with F vs P in both GPC and PPC subgroups (Table). Safety was consistent with previous reports; no differences were observed between prognostic subgroups. Table: 31P
Efficacy outcomes in FRESCO-2 by treatment arm and baseline prognostic factors
| GPC subgroup (n=91) | PPC subgroup (n=600) | |||
| Fruquintinib + BSC (n=52) | Placebo + BSC (n=39) | Fruquintinib + BSC (n=409) | Placebo + BSC (n=191 | |
| Median OS (months) | 11.0 | 6.3 | 7.1 | 4.3 |
| HR (95% CI); p-value | 0.474 (0.243, 0.923); p=0.0134 | 0.633 (0.519, 0.773); p<0.0001 | ||
| Median PFS (months) | 4.8 | 1.9 | 3.6 | 1.8 |
| HR (95% CI); p-value | 0.273 (0.156, 0.477); p<0.0001 | 0.310 (0.254, 0.378); p<0.0001 | ||
| Median time to deterioration to ECOG PS ≥2 (months) | 9.9 | 5.5 | 6.2 | 2.8 |
| HR (95% CI); p-value | 0.355 (0.149, 0.752); p=0.008 | 0.537 (0.419, 0.688); p<0.000 |
Conclusions
In the heavily pretreated pt population of FRESCO-2, the number of metastatic sites and time from diagnosis of metastasis to randomization are important prognostic factors. In pts with more indolent or more aggressive disease, F was effective in improving OS, PFS, and delay to PS deterioration vs P.
Clinical trial identification
NCT04322539.
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
Takeda Pharmaceuticals U.S.A., Inc.
Disclosure
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. 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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, Invited Speaker: Advanced Accelerator Applications International; Non-Financial Interests, Advisory Role, Adult Oncology Steering Board Membership: Epic. A. Sartore Bianchi: Financial Interests, Personal, Advisory Board: Amgen, Servier, Novartis; Financial Interests, Personal, Invited Speaker: Bayer, Guardant Health, Pierre Fabre. V. Randrian: Non-Financial Interests, Invited Speaker: Takeda; Non-Financial Interests, Research Grant: Fondation Servier, Novartis; Financial Interests, Advisory Board: Takeda, MSD. C. 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Kasper-Virchow: Financial Interests, Invited Speaker: BMS, MSD, Amgen, AstraZeneca, Merck Healthcare, Servier, Lilly, Onkowissen.de, ArtTempi, Takeda; Financial Interests, Advisory Board: BMS, MSD, Amgen, AstraZeneca, Merck Healthcare, Servier, Lilly, Onkowissen.de, ArtTempi, Takeda, Seagen, Novartis; Financial Interests, Research Grant: BMS, Lilly, Roche; Non-Financial Interests, Principal Investigator: Novartis, BMS, Amgen. 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. D. 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Editor for ESMO Open and Ann Oncol: Elsevier; Financial Interests, Personal, Other, Role as Associate Editor Clin Colorect Cancer: Elsevier; Financial Interests, Institutional, Other, DSMB chair: Sanofi (Genzyme); Financial Interests, Institutional, Invited Speaker: 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. D. Tougeron: Financial Interests, Personal, Advisory Board: AstraZeneca, Sanofi, Amgen, MSD, Roche, Servier, Pierre Fabre, BMS, Bayer; Non-Financial Interests, Member of Board of Directors: Federation Francophone de Cancerologie Digestive. C. Dong: Financial Interests, Full or part-time Employment: Takeda. I. Carton: Financial Interests, Full or part-time Employment: Hutchmed. N.A. Dasari: Financial Interests, Personal, Advisory Board: Hutchmed, AAA, Personalis, Illumina, Takeda; Financial Interests, Institutional, Invited Speaker: Hutchmed, Eisai, Enterome, Guardant Health, Natera, Xencor, Taiho. All other authors have declared no conflicts of interest.