Abstract 531P
Background
Liver metastases (LM) represent a significant challenge in colorectal cancer (CRC) management and are associated with poor prognosis. This study aimed to evaluate the prognostic significance of LM, KRAS mutations (MT), and race status in metastatic CRC patients (pts) treated with salvage-line therapies, trifluridine/tipiracil or regorafenib (TToR), or placebo, using data from the ARCAD CRC database.
Methods
Dara from four placebo-controlled randomized trials (CORRECT, RECOURSE, CONCUR, and TERRA) conducted in a salvage-line setting were pooled. The survival outcomes, overall survival (OS) and progression-free survival (PFS), were assessed using Kaplan-Meier estimates, adjusted Cox models on ECOG PS, age, and gender, along with interaction tests.
Results
Among the 1425 TToR- and 712 placebo-treated patients (pts), 73.4% pts had LM versus (vs) NLM, 50.9% KRAS MT vs wild-type (WT) and 57.6% were non-Asian vs Asian. The following table presents the results of subgroup analysis for OS and PFS among pts receiving TToR or placebo. In TToR- and placebo-treated pts, better OS and PFS were observed in NLM compared to LM pts. TToR-treated pts with KRAS MT had worse OS compared to those with KRAS WT, whereas no significant difference was observed in placebo-treated pts. There was no significant difference in OS and PFS between Asian and non-Asian pts in both treatment groups. Among TToR-treated pts with LM, worse OS and PFS were found in those with KRAS MT, interaction tests were non-significant (OS P=.374; PFS P=.622) and worse OS was found in non-Asian pts compared to Asian pts, and the interaction test was significant (P=.007).
Conclusions
In mCRC pts receiving TToR and placebo in a salvage-line setting, LM is a poor prognostic factor for both group, MT KRAS is a poor prognostic factor only for pts receiving TToR, while race is not a prognostic factor. Table: 531P
Hazard ratio (HR) and 95% confidence intervals (CI) for OS and PFS
| HR (95%CI) P | ||||
| TToR | Placebo | |||
| OS | PFS | OS | PFS | |
| NLM vs LM | .43 (.37-.51) Clinical trial identificationEditorial acknowledgementLegal entity responsible for the studyThierry André. FundingA.R.CA.D Foundation. DisclosureT. André: Financial Interests, Personal, Advisory Board, Advosiry Board on February 12, 2021: Astellas pharma; Financial Interests, Personal, Advisory Board, Advisory Board on February 2021: Kaleido Biosciences; Financial Interests, Personal, Invited Speaker, and advisory board 2021: Amgen; Financial Interests, Personal, Invited Speaker, Ivited speaker in a symposuim december 2020: AstraZeneca; Financial Interests, Personal, Advisory Board, and consultant fees and consultant contract 2021 and 2022: Bristol-Myers Squibb; Financial Interests, Personal, Advisory Board, Advisory board in January 2020: Clovis; Financial Interests, Personal, Advisory Board, Advisory board in january 2020: Gritstone Oncology; Financial Interests, Personal, Advisory Board, Advisory board 2020: Haliodx; Financial Interests, Personal, Advisory Board, and consultant fees/consultant contract and invited speaker: MSD Oncology; Financial Interests, Personal, Invited Speaker, and other: Pierre Fabre; Financial Interests, Personal, Invited Speaker, in an symposuim in 2020: Roche; Financial Interests, Personal, Invited Speaker, in a meeting in 2019: Ventana; Financial Interests, Personal, Invited Speaker, In a educational meeting in 2019: Sanofi; Financial Interests, Personal, Advisory Board, in a symposuim in 2020: Servier; Financial Interests, Personal, Advisory Board, Consultant with personnal fees and invited speaker: Servier; Financial Interests, Personal, Advisory Board, in 2019: GSK; Financial Interests, Personal, Invited Speaker, in 2020 and 2021: GSK; Financial Interests, Personal, Invited Speaker, Virtual symposuimLecture: 1 MSI-H CRC: Implementation of Immunotherapy in clinical practice (30 minutes) – (this will be pre-recorded)Q&A – Live Q&A – (10 minutes) (on July 2, 2021): MSD Oncology; Financial Interests, Personal, Invited Speaker, June 2022: Sanofi; Financial Interests, Personal, Advisory Board, Contract 2021, 2022, 2023: Merck & Co., Inc; Financial Interests, Personal, Advisory Board, Contrat 2019, 2020, 2021, 2022: BMS; Financial Interests, Personal, Advisory Board, Contract 2021: Gritstone Oncologie; Financial Interests, Personal, Invited Speaker, June 2022 and June 2023 during ESMO GI meeting: Seagen; Financial Interests, Personal, Writing Engagement, Contract of consulting 2021 and 2022 and 2023: MSD Oncology; Financial Interests, Personal, Advisory Board, September 2022: GSK, Seagen; Financial Interests, Personal, Writing Engagement, Contract of consulting 2022 and 2023: GSK; Financial Interests, Personal, Writing Engagement, Contract of consulting 2022: Nordic Pharma; Financial Interests, Personal, Invited Speaker, October 2022: Merck Serono; Financial Interests, Personal, Other, Educationnal in 2022: Roche; Financial Interests, Personal, Other, Contract of consulting 2020, 2021, 2022,2023: Servier; Financial Interests, Personal, Advisory Board, Gilead Sciences Global GI Advisory Board on January 18, 2023: Aptitude Health, Glilead; Financial Interests, Personal, Other, Consultant like member of the SGNTUC-029 Steering Committee (the “Steering Committee”) Services related to the Company’s Study titled “An Open-label Randomized Phase 3 Study of Tucatinib in Combination with Trastuzumab and mFOLFOX6 versus mFOLFOX6 given with or without either Cetuximab or Bevacizumab as First-line Treatment for Subjects with HER2+ Metastatic Colorectal Cancer” (collectively, the “Services”).Including teleconferences and board preparation befor the board (6h)Participation of the Board on September 2022 inParis, September 10, 2022 MOUNTAINEER-03 Steering Committee Meeting during ESMO: Seagen; Financial Interests, Personal, Other, Consultant like member of the to be a member of the Colorectal Program Scientific Advisory Committee (SAC). In charges for reviewing V940 Pembro on Engagezone (as per your contract in ref).and also an inrtview about Pembrolizumab for MSI/dMMR Metastaic colo-rectal 2023: MSD Oncology; Financial Interests, Personal, Advisory Board, but also formation for the takeda team, and consultant for TakedaContract beetween 1 sept 2023 and 15 october 2024: Takeda; Financial Interests, Personal, Advisory Board, Board Meeting (October 19, 2023): Abbvie; Financial Interests, Personal, Invited Speaker, Emerging Role of Biomarkers in Gastrointestinal Cancers Webcast Engagement reference : Wenibar: MSD; Financial Interests, Personal, Invited Speaker, Preparation and resentation at the Seagen ESMO GI 2023 Scientific Exchange HER2 as an emerging target for the treatment of mCRC in the context MOUNTAINEER03: Seagen; Financial Interests, Personal, Advisory Board, Fruquitinib: Takeda; Financial Interests, Personal, Invited Speaker, Oral speaker in a Symposuim 2 and 3 February 2024, GI ancer MSI: MSD; Financial Interests, Personal, Invited Speaker, Management of CRC: Aptitude Health; Financial Interests, Personal, Invited Speaker, symposuim JFHOD GI CancerPARIS15 03-2024: Servier; Financial Interests, Institutional, Coordinating PI, PI Garnet study: GSK; Financial Interests, Institutional, Coordinating PI, Keynote 164 and 171 and 811 and C08: MSD; Financial Interests, Institutional, Coordinating PI, BMS CA209-8HW, BMS CA209-142, BMS CA209-577: BMS; Financial Interests, Institutional, Coordinating PI, SPOTLIGHT study: Astellas; Financial Interests, Personal, Steering Committee Member, and internationnal PI (trial chair Solstice study): Servier; Financial Interests, Personal, Steering Committee Member, MOUNTAINEER and MOUNTAINEER-03 study (PI for France) 2022, 2023: Seagen; Financial Interests, Institutional, Local PI, A RANDOMIZED, OPEN-LABEL, PHASE 2 STUDY OF BOTENSILIMAB (AGEN1181) AS MONOTHERAPY AND IN COMBINATION WITH BALSTILIMAB (AGEN2034) OR INVESTIGATOR’S CHOICE STANDARD OF CARE (REGORAFENIB OR TRIFLURIDINE AND TIPIRACIL) FOR THE TREATMENT OF REFRACTORY METASTATIC COLORECTAL CANCER: Agenus; Financial Interests, Institutional, Local PI, Study wuith traztuzumab derxtecan in mCRC C study: Daichi; Non-Financial Interests, Member of Board of Directors, Investigator: Gercor group; Non-Financial Interests, Member of Board of Directors, President since october 2022: ARCAD Foundation; Other, DMC Meeting by Teleconference on November 7, 2023 5member of steering comittee of A randomized Phase 2 Study of ompenaclid versus placebo in combination with FOLFIRI plus bevacizumab in patients withpreviously treated RAS mutant advanced or metastatic colorectal cancer (RGX-202-002): Inspira. Q. Shi: Financial Interests, Personal, Advisory Role: Yiviva Inc, Regeneron Pharmaceuticals Inc., Hoosier Cancer Research Network, Kronos Bio, Mirati Therapeutics Inc. ; Financial Interests, Institutional, Research Funding: Regeneron, BMS, Roche/Genentech, Janssen, Novartis. 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.. 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. A. Grothey: Financial Interests, Personal, Invited Speaker: Total Health, Cardinal Health; Financial Interests, Institutional, Local PI: OBI Pharmaceuticals, Natera, CARIS, Guardant Health; Non-Financial Interests, Principal Investigator: Bayer; Non-Financial Interests, Advisory Role: Daiichi, Natera. B. Chibaudel: Financial Interests, Personal, Advisory Board: Amgen, Bayer, BeiGene, Biocartis, Lilly, Merck, MSD, Pfizer, Pierre Fabre, Roche, SeqOne, Sanofi, Servier, Takeda. All other authors have declared no conflicts of interest. 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