Abstract 93P
Background
In the global, randomized, double-blind, phase 3 FRESCO-2 study (NCT04322539), treatment with F + BSC significantly improved overall survival (OS) and progression-free survival (PFS) vs P + BSC, with a favorable toxicity profile in patients (pts) with refractory mCRC. Here we report efficacy and safety data according to race for Asian and non-Asian patient subgroups.
Methods
Patients in USA, Europe, Japan, and Australia were randomized 2:1 to receive F (5 mg) or matching P, PO QD, for 21 days every 28 days + BSC. Eligible pts had received prior chemotherapy, anti-VEGF therapy and, if RAS wild type, anti-EGFR therapy; if BRAFV600E mutant or MSI-H, an appropriate targeted regimen; and prior trifluridine/tipiracil and/or regorafenib. Primary endpoint was OS.
Results
Overall, 61 Asian pts (6 in USA, 55 in Japan) and 594 non-Asian pts were enrolled. Asian vs non-Asian pts were younger (64 vs 52% aged <65 years), had a higher proportion of ECOG PS of 0 (59 vs 41%), and a higher proportion had received >3 lines of prior therapy for metastatic disease (80 vs 71%); pt characteristics were generally balanced between treatment arms within subgroups. OS was improved with F + BSC vs P + BSC in Asian (median 7.1 vs 4.7 months; HR 0.38, 95% CI 0.17–0.83) and non-Asian pts (median 7.6 vs 4.8 months; HR 0.70, 95% CI 0.57–0.86). PFS was also improved with F + BSC vs P + BSC in both Asian and non-Asian pts (Table). The incidence of TEAEs with F + BSC vs P + BSC was 98 vs 84% in Asian pts and 99 vs 94% in non-Asian pts. Grade ≥3 TEAEs are shown in the table. Table: 93P
FRESCO-2 efficacy and safety data overall and by Asian and non-Asian race subgroups
| ITT population | F + BSC n=461 | P + BSC n=230 | ||
| Median OS, months HR (95%CI) | 7.4 | 4.8 | ||
| 0.66 (0.55–0.80); p<.001 | ||||
| Median PFS, months HR (95%CI) | 3.7 | 1.8 | ||
| 0.32 (0.27–0.39); p<.001 | ||||
| Asian pts | Non-Asian pts | |||
| F + BSC n=43 | P + BSC n=18 | F + BSC n=390 | P + BSC n=204 | |
| Median OS, months HR (95%CI) | 7.1 | 4.7 | 7.6 | 4.8 |
| 0.38 (0.17–0.83) | 0.70 (0.57–0.86) | |||
| Median PFS, months HR (95%CI) | 3.6 | 1.7 | 3.7 | 1.9 |
| 0.29 (0.14–0.58) | 0.32 (0.26–0.39) | |||
| Safety population | Asian pts* | Non-Asian pts | ||
| F + BSC n=42 | P + BSC n=19 | F + BSC n=387 | P + BSC n=202 | |
| Grade ≥3 TEAEs, % | 69% | 32% | 61% | 51% |
*One patient assigned to fruquintinib arm received placebo instead.
Conclusions
There was a clinically meaningful improvement in OS and PFS with F + BSC vs P + BSC in both Asian and non-Asian pts. Despite similar median OS between groups, the HR was different in the Asian subgroup; more results from sensitivity analyses may be reported. The safety and efficacy subgroup analysis results were consistent with the overall FRESCO-2 population and with the established monotherapy profile of F.
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
HUTCHMED.
Disclosure
D. Kotani: Financial Interests, Personal, Other, Honoraria: Takeda, Chugai, Lilly, MSD, Ono, Taiho, Bristol Myers Squibb, Daiichi Sankyo, Pfizer, Eisai, Merckbiopharma, Sysmex, Seagen, Novartis; Financial Interests, Personal, Research Funding: Ono, MSD, Novartis, Servier, Janssen, IQVIA, Syneoshealth, Cimic, Cimicshiftzero. T. Yoshino: Financial Interests, Personal, Other, Honoraria: Bayer Yakuhin, Ltd., Chugai Pharmaceutical Co., Ltd., Merck Biopharma Co., Ltd, MSD K.K., Ono Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd ; Financial Interests, Personal, Research Funding: Amgen K.K., Chugai Pharmaceutical Co., Ltd., Daiichi Sankyo Co., Ltd., Eisai Co., Ltd., FALCO biosystems Ltd., Genomedia Inc., Molecular Health GmbH, MSD K.K., Nippon Boehringer Ingelheim Co., Ltd., Ono Pharmaceutical Co., Ltd., Pfizer Japan Inc., Roche Diagnostics K.K., Sanofi K.K., Sysmex Corp., Taiho Pharmaceutical Co., Ltd.; Financial Interests, Personal, Speaker, Consultant, Advisor, Consulting fees: Sumitomo Corp. A.S. Paulson: Financial Interests, Institutional, Research Grant, Receiving grants or contracts for clinical trials: Ipsen, Bristol Myers Squibb, Exelixis, HUTCHMED, Taiho, Lilly, AstraZeneca, Incyte, Deciphers, G1 Therapeutics, Zentalkis, Tempus, Camurus, Relay Therapeutics, Nucana, Merck, Bayer, Sotio, Innovations Cellular Therapeutics; Financial Interests, Personal, Other, Educational event fees: Ideo Oncology, MJH Life Sciences; Financial Interests, Personal, Other, Travel support: Pfizer; Financial Interests, Personal, Advisory Board, Participation on a data safety monitoring or advisory board: Amgen, Bristol Myers Squibb, Eisai, Ipsen, AAA, Exelixis, Pfizer, QED, Lilly, Mirati, HUTCHMED, Astellas, Incyte, AADi, Stromatis, EMD, Serono; Financial Interests, Personal, Stocks/Shares: Aptose, Actinium, Alexion; Financial Interests, Personal, Other, Payment for medical writing services: Bayer, Ipsen, HUTCHMED, Exelixis. T. Masuishi: Financial Interests, Institutional, Research Grant, Grants or contracts: MSD, Daiichi Sankyo, Ono, Novartis, Amgen, Syneos Health Clinical, Boehringer Ingelheim, Pfizer, Cimic Shift Zero, Eli Lilly; Financial Interests, Personal, Other, Payment or honoraria for lectures, presentations, speakers' bureaus, manuscript writing, or educational events: Takeda, Chugai, Merck Bio Pharma, Taiho, Bayer, Lilly Japan, Yakult Honsha, Sanofi, Daiichi Sankyo, Ono, Bristol Myers Squibb. H. Hochster: Financial Interests, Personal, Speaker, Consultant, Advisor: Merck, Processa, TRIGR; Financial Interests, Personal, Invited Speaker: Natera; Financial Interests, Personal, Other, data safety monitoring or advisory board: Seattle Genetics, Genentech. J. Krauss: Financial Interests, Institutional, Research Grant, Grants or contracts to their institution: Genentech, Bristol Myers Squibb, Amgen, Isofol Medical, Novartis, Tempest Therapeutics, MedImmune/AstraZeneca, AbbVie, MedImmune, Icon, Turning Point Therapeutics. Y. Sunakawa: Financial Interests, Personal, Speaker, Consultant, Advisor: Ono Pharmaceutical Co. Ltd., Merck Biopharma Co., Ltd, Guardant Health Japan Co; Financial Interests, Personal, Other, Honoraria: Bristol Myers Squibb Co. Ltd, Bayer Yakuhin Ltd., Eli Lilly Japan K.K., MSD K.K, Ono Pharmaceutical Co. Ltd., Chugai Pharmaceutical Co. Ltd., Daiichi Sankyo Co. Ltd, Takeda Pharmaceutical Co. Ltd., Merck Biopharma Co., Ltd, Guardant Health Japan Co., Sysmex Co., Taiho Pharmaceutical Co. Ltd; Financial Interests, Personal, Research Funding: Chugai Pharmaceutical Co. Ltd, Takeda Pharmaceutical Co. Ltd., Eli Lilly Japan K.K., Sanofi, Taiho Pharmaceutical Co. Ltd., Ohtsuka Pharmaceutical Co. A. Takashima: Financial Interests, Personal, Research Grant: Takeda, Ono Pharmaceutical, Merck Sharp & Dohme, Bristol Myers Squibb, Isofol Medical AB, Hutchison Medipharma, Incyte Corporation, Pfizer Inc, Daiichi Sankyo; Financial Interests, Personal, Other, Personal fees: Eli Lilly, Taiho Pharmaceutical, Ono Pharmaceutical, Chugai Pharmaceutical, Takeda, Merck Serono, Merck Sharp & Dohme. K. Yamazaki: Financial Interests, Personal, Other, Personal fees and honoraria: Chugai Pharmaceutical, Daiichi Sankyo, Yakult Honsha, Takeda, Bayer, Merck Serono, Taiho Pharmaceutical, Eli Lilly, Sanofi, Ono Pharmaceutical, Merck Sharp & Dohme, Bristol Myers Squibb. H. Kawakami: Financial Interests, Personal, Speaker, Consultant, Advisor: Bristol Myers Squibb Co. Ltd., Eli Lilly Japan K.K., MSD K.K., Ono Pharmaceutical Co. Ltd., Daiichi Sankyo Co. Ltd., Taiho Pharmaceutical Co. Ltd.; Financial Interests, Personal, Other, Honoraria: Bristol Myers Squibb Co. Ltd., AstraZeneca K.K, Eli Lilly Japan K.K., MSD K.K., Ono Pharmaceutical Co. Ltd., Chugai Pharmaceutical Co. Ltd., Takeda Pharmaceutical Co. Ltd., Taiho Pharmaceutical Co. Ltd, Daiichi Sankyo Co. Ltd.; Financial Interests, Personal, Other, Lecture fees: Bristol Myers Squibb Co. Ltd, Eli Lilly Japan K.K., MSD K.K, Ono Pharmaceutical Co. Ltd., Daiichi Sankyo Co. Ltd., Chugai Pharmaceutical Co. Ltd, Takeda Pharmaceutical Co. Ltd., Taiho Pharmaceutical Co. Ltd.; Financial Interests, Personal, Research Funding: Bristol Myers Squibb Co. Ltd., Chugai Pharmaceutical Co. Ltd., Taiho Pharmaceutical Co. Ltd., Eisai Co. Ltd. T. Nishina: Financial Interests, Personal, Other, Honoraria: Ono Pharmaceuticals, Taiho Pharmaceuticals, Takeda Pharmaceuticals, Chugai Pharmaceuticals, Daiichi Sankyo. Y. Komatsu: Financial Interests, Personal, Research Grant: Takeda, Chugai, Nihonkayaku, Nipro, Taiho Pharmaceutical, Ono Pharmaceutical, Nippon Zoki, Shionogi, EPS, IQVIA, Astellas, Eisai, Merck Sharp & Dohme, Yakult, Daiichi Sankyo, Eli Lilly, Sanofi, Bristol Myers Squibb; Financial Interests, Personal, Research Funding: Takeda, Chugai, Nihonkayaku, Nipro; Financial Interests, Personal, Speaker’s Bureau, Speakers bureau membership: Chugai, Nihonkayaku; Financial Interests, Personal, Other, Personal fees: Chugai, Nihonkayaku, Taiho Pharmaceutical, Ono Pharmaceutical, Yakult, Daiichi Sankyo, Eli Lilly, Bayer, Pfizer, Bristol Myers Squibb, Asahi Kasei. T. Esaki: Financial Interests, Personal, Research Grant: MSD, Novartis, Dainippon Sumitomo, Ono, Daiichi Sankyo, Astellas, Astellas Amgen Biopharma, Parexel, Chugai, Quintiles, Syneos Health, PfIzer; Financial Interests, Personal, Other, Honoraria: MSD, Tahio, Ono, Daiichi Sankyo, Lilly, Chugai, Sanofi. C. Eng: Financial Interests, Personal, Speaker, Consultant, Advisor: Amgen, Bayer, Ca Institute of Regenerative Medicine, Elevation, GE, GSK, IGM, Merck, Natera, Pfizer, Taiho, Seagen ; Financial Interests, Institutional, Research Funding: Merck, Hutchi-Med, Pfizer, Janssen, Gritstone. N.A. Dasari: Financial Interests, Institutional, Research Grant: Hutchmed, Guardant Health, Natera Inc, Eisai, Crinetics, AAA / Novartis; Financial Interests, Personal, Advisory Board: Hutchmed, Crinetics, Voluntis, AAA / Novartis, Personalis Inc. Z. Yu: Financial Interests, Personal, Full or part-time Employment: Takeda. L. Chen: Financial Interests, Personal, Full or part-time Employment: Takeda. T. Yang: Financial Interests, Personal, Full or part-time Employment: HUTCHMED. W. Schelman: Financial Interests, Personal, Full or part-time Employment: HUTCHMED. T. Satoh: Financial Interests, Personal, Other, Honoraria: Daiichi Sankyo, Ono Pharmaceutical, Bristol Myers Squibb, Elli Lilly; Financial Interests, Personal, Research Funding: Daiichi Sankyo, Ono Pharmaceutical, Bristol Myers Squibb, MSD, Hutch Med, Taiho Pharmaceutical, Shionogi Pharmaceutical, Elli Lilly.
Resources from the same session
397P - Comparison between Y-site co-infusion versus standard dexamethasone for preventing hypersensitivity reactions from oxaliplatin administration: A randomized controlled trial
Presenter: jarearnjit Phavirunsiri
Session: Poster Display
Resources:
Abstract
398P - Evaluation of the effectiveness of denosumab therapy giant cell tumor of the pelvis
Presenter: Abbos Nurjabov
Session: Poster Display
Resources:
Abstract
399P - Long-term outcomes of patients with gastric cancer who received the best supportive care without any anticancer treatment
Presenter: Yohei Arihara
Session: Poster Display
Resources:
Abstract
401TiP - Oral opioid vs intravenous patient-controlled analgesia (PCA) with hydromorphone bolus-only or continuous infusion to maintain analgesia for severe cancer pain: A randomized phase III trial
Presenter: Cheng Huang
Session: Poster Display
Resources:
Abstract
407P - K-TrackTM: A streamlined personalized assay to detect molecular residual disease in solid tumors
Presenter: Nam Vo
Session: Poster Display
Resources:
Abstract
408P - Increased EGFR and MET expression and corresponding tumor microenvironment (TME) change in hepatocellular carcinoma (HCC) tissues after sorafenib (Sora) treatment
Presenter: Chia Jui Yen
Session: Poster Display
Resources:
Abstract
410P - Systematic evaluation of cell-free DNA fragmentation patterns for cancer diagnosis and enhanced cancer detection through integration of multiple fragmentations
Presenter: Xiangy-Yu Meng
Session: Poster Display
Resources:
Abstract
412P - Multiplex digital spatial profiling (DSP) of protein reveals distinct immune and molecular phenotypes in hepatocellular carcinoma
Presenter: Chia Jui Yen
Session: Poster Display
Resources:
Abstract
413P - Clinical utility of advanced features provided by circulating tumor DNA-based comprehensive genomic profiling
Presenter: Young-gon Kim
Session: Poster Display
Resources:
Abstract
414P - Landscape of ERBB2 mutations in advanced cancers (AC) using circulating tumor DNA (ctDNA) next-generation sequencing (NGS) in Asia and Middle East (AME)
Presenter: Byoung Chul Cho
Session: Poster Display
Resources:
Abstract