Abstract 444P
Background
Previous trials have demonstrated that bevacizumab and fluoropyrimidine combination is effective and well-tolerated in older patients with metastatic colorectal cancer (mCRC pts). In this randomized phase II trial, we investigated whether the addition of aflibercept to LV5FU2 regimen is effective and well tolerated in mCRC pts not fit for irinotecan/oxaliplatin-based chemotherapy.
Methods
The main eligibility criteria were age ≥ 65 and WHO performance status <2. Randomization was stratified according to thymidylate synthase (TS)-5’UTR germline polymorphism, centrally determined, as a potential predictive/prognostic biomarker of 5-FU-based chemotherapy. Simplified LV5FU2 regimen, preceded or not by 4 mg/kg aflibercept, was administered every 14 days. The primary objective was the 6-month progression-free survival rate. Secondary objectives were safety, quality of life, overall survival, and the impact of TS-5’UTR polymorphism.
Results
Until April 2020, 114/118 pts were included, 56 in arm A (5FU-aflibercept), 58 in arm B (5FU alone). Median of age was 81 years old (range 67-92), 81% pts were more than 75 years old and 62% men. Köhne score in arm A/B: low risk 37.5/45% pts, intermediate 48/53% pts, high 14/2% pts. The TS-5UTR 3R3R polymorphism was present in 23% pts. In 59% pts, the number of metastatic sites was >1; median BMI was 25; 64% pts had WHO performance status 1; the primary tumor location was right colon in 41% pts, rectum in 18%; the metastases involved all hepatic segments in 64% of pts, both lung in 55%, and/or peritoneum in 20%; the RAS status was mutated in 48/76 pts with data currently available, the BRAF status mutated in 7/60 pts. All the above data seemed similar in both arms. Primary tumor was resected in 46% of arm A pts, 67% in arm B. The toxicity was expected with more grade 3-4 toxicities in arm A: at least 1 toxicity in 70% vs 49% pts, hypertension in 41% vs 20% pts, proteinuria in 15% vs 0 pts, without increase of thromboembolic or hemorrhagic events.
Conclusions
This trial will provide for the first time safety and efficacy results of 5FU versus 5FU plus aflibercept in very old patients with a median age over 80 years.
Clinical trial identification
EudraCT 2014-001837-10.
Editorial acknowledgement
Legal entity responsible for the study
Fédération Francophone de Cancérologie Digestive.
Funding
Sanofi.
Disclosure
J.L. Legoux: Advisory/Consultancy, Research grant/Funding (self), Travel/Accommodation/Expenses: Novartis; Advisory/Consultancy, Travel/Accommodation/Expenses: Servier; Speaker Bureau/Expert testimony: Keocyt; Research grant/Funding (self): Pfizer; Research grant/Funding (institution): Sanofi; Travel/Accommodation/Expenses: Ipsen; Travel/Accommodation/Expenses: Merck-Serrono. N. Barriere: Advisory/Consultancy, Travel/Accommodation/Expenses: Amgen; Travel/Accommodation/Expenses: MerckSerrono; Advisory/Consultancy, Travel/Accommodation/Expenses: Sanofi. D. Tougeron: Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: BMS; Honoraria (self), Research grant/Funding (institution): Novartis; Honoraria (self), Research grant/Funding (institution): Merck Serrono; Advisory/Consultancy, Travel/Accommodation/Expenses: MSD; Honoraria (self), Advisory/Consultancy: Astra Zeneca; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Servier; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Sanofi; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Roche; Honoraria (self), Travel/Accommodation/Expenses: Amgen; Honoraria (self): Ipsen. V. Bourgeois: Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Servier; Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Sanofi; Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Merck Serrono; Advisory/Consultancy: Esai; Travel/Accommodation/Expenses: Roche; Travel/Accommodation/Expenses: Sandoz; Research grant/Funding (institution): Teva; Travel/Accommodation/Expenses: Amgen. D. Malka: Honoraria (self): Amgen; Honoraria (self): Bayer; Honoraria (self): MSD; Honoraria (self): Merck Serrono; Honoraria (self): Servier; Honoraria (self): Agios; Honoraria (self): Incyte; Honoraria (self): Novartis; Honoraria (self): Sanofi; Honoraria (self): Roche; Honoraria (self): HalioDX; Honoraria (self): Pierre Fabre Oncologie. T. Aparicio: Speaker Bureau/Expert testimony: Sanofi; Honoraria (self), Travel/Accommodation/Expenses: Roche; Honoraria (self): Amgen; Honoraria (self): Ipsen; Honoraria (self): Servier; Honoraria (self): Bioven; Travel/Accommodation/Expenses: Bayer. F. Khemissa Akouz: Honoraria (self), Travel/Accommodation/Expenses: Roche; Honoraria (self), Travel/Accommodation/Expenses: Ipsen; Advisory/Consultancy, Travel/Accommodation/Expenses: Sanofi; Travel/Accommodation/Expenses: Fresinius; Travel/Accommodation/Expenses: Bayer; Travel/Accommodation/Expenses: Novartis. C. Lepage: Speaker Bureau/Expert testimony: Bayer; Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Novartis; Speaker Bureau/Expert testimony: Amgen; Advisory/Consultancy: AAA; Travel/Accommodation/Expenses: Ipsen. V. Boige: Speaker Bureau/Expert testimony: Bayer; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Merck Serrono; Speaker Bureau/Expert testimony: Amgen; Advisory/Consultancy, Speaker Bureau/Expert testimony: Sanofi; Speaker Bureau/Expert testimony: Daiichi Sankyo; Speaker Bureau/Expert testimony: Roche; Speaker Bureau/Expert testimony: MSD; Advisory/Consultancy, Speaker Bureau/Expert testimony: Ipsen; Advisory/Consultancy: Prestizia; Advisory/Consultancy, Speaker Bureau/Expert testimony: Eisai. All other authors have declared no conflicts of interest.