A Phase 1 Study of Cabozantinib and Trifluridine/Tipiracil in Metastatic Colorectal Adenocarcinoma.

Autor: Dayyani F; Division of Hematology/Oncology, Department of Medicine and Chao Family Comprehensive Cancer Center, University of California Irvine, Orange, CA. Electronic address: fdayyani@hs.uci.edu., Balangue J; Division of Hematology/Oncology, Department of Medicine and Chao Family Comprehensive Cancer Center, University of California Irvine, Orange, CA., Valerin J; Division of Hematology/Oncology, Department of Medicine and Chao Family Comprehensive Cancer Center, University of California Irvine, Orange, CA., Keating MJ; Division of Hematology/Oncology, Department of Medicine and Chao Family Comprehensive Cancer Center, University of California Irvine, Orange, CA., Zell JA; Division of Hematology/Oncology, Department of Medicine and Chao Family Comprehensive Cancer Center, University of California Irvine, Orange, CA., Taylor TH; Department of Epidemiology & Biostatistics, Irvine, CA., Cho MT; Division of Hematology/Oncology, Department of Medicine and Chao Family Comprehensive Cancer Center, University of California Irvine, Orange, CA.
Jazyk: angličtina
Zdroj: Clinical colorectal cancer [Clin Colorectal Cancer] 2024 Mar; Vol. 23 (1), pp. 67-72. Date of Electronic Publication: 2023 Nov 27.
DOI: 10.1016/j.clcc.2023.11.001
Abstrakt: Introduction: This study determined the safety and recommended phase 2 dose (RP2D) of the multikinase inhibitor cabozantinib in combination with trifluridine/tipiracil (FTD/TPI) in refractory metastatic colorectal carcinoma (mCRC).
Patients and Methods: Single institution investigator-initiated phase 1 study using 3+3 design. Eligible mCRC patients had received prior standard regimens. Cabozantinib was given orally (p.o.) at 20 mg (dose level [DL] 0) or 40 mg (DL 1) daily on days 1-28, and FTD/TPI p.o. at 35 mg/m 2 on days 1-5 and 8-12 every 28 days. Prophylactic growth-factor support was allowed.
Results: Fifteen patients were enrolled. Median age 56 years (31-80), male (12/15), ECOG 0/1 = 9/6. Three patients were treated at DL 0 and another nine were treated at DL 1, none exhibiting a DLT. Most common any grade (G) treatment related adverse events (TRAE) were diarrhea (50%), nausea (42%), neutropenia (42%), fatigue (33%), and rash (25%). G3-4 TRAE were neutropenia (25%) and thrombocytopenia, hypokalemia, and weight loss (each 8%). No serious TRAE or G5 were reported. The RP2D was determined to be DL 1. Median PFS was 3.8 months (95% CI 1.9-6.8) and disease control rate was 86.7%.
Conclusion: The combination of cabozantinib and FTD/TPI is feasible and tolerable at standard doses with the use of growth factors and showed encouraging clinical activity in refractory mCRC.
Clinicaltrials: GOV: NCT04868773.
Competing Interests: Disclosure FD has received research grants (to the institution) from AstraZeneca, Bristol-Myers Squibb, Merck, Genentech/Roche, Taiho, Exelixis, Trishula, Leap Therapeutics, has received a speaker honorarium from Amgen, Eisai, Ipsen, Exelixis, Sirtex, Deciphera, Ipsen, Natera, and has received a consultancy honorarium from Natera, QED, Eisai, Exelixis, Genentech/Roche. MTC has received research grants (to the institution) from Bristol-Myers Squibb, a speaker honorarium from Pfizer, Natera, Taiho, BMS, AstraZeneca, a consultancy honorarium from Amgen, Incyte, Eisai, Ipsen, Astellas, Taiho, Exelixis, QED, I-Mab, Tempus, Seattle Genetics, HelioDx, Bayer, AstraZeneca, Genentech/Roche, Pfizer, Natera, Taiho, BMS, Basilea. JAZ has received a consultancy honorarium from Tempus and Exact Sciences, has received research grants (to the institution) from Halozyme and Merck. JV has received a consultancy honorarium from Astrazeneca. The other authors declare that they have no conflict of interest.
(Copyright © 2023 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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