A Phase II Study Investigating Cabozantinib in Patients with Refractory Metastatic Colorectal Cancer (AGICC 17CRC01).
Document Type
Article
Publication Date
10-1-2022
Publication Title
Cancer Res Commun
Keywords
washington; swedish; swedish cancer
Abstract
PURPOSE: Multi-tyrosine kinase inhibitors (TKI) have shown clinical activity in patients with metastatic colorectal cancer. Cabozantinib, a multi-TKI, exhibited potent antitumor activity superior to regorafenib in preclinical colorectal cancer patient-derived tumor xenograft models. This phase II study aimed to investigate cabozantinib, a multi-TKI, in patients with refractory, metastatic colorectal cancer (mCRC).
EXPERIMENTAL DESIGN: A nonrandomized, two-stage, phase II clinical trial evaluating 12-week progression-free survival (PFS) was conducted in eight cancer centers across the United States between May 2018 and July 2020.
RESULTS: A total of 44 patients were enrolled between May 2018 and May 2019, 40 of which were response evaluable. Of the total 769 reported adverse events (AE), 93 (12%) were ≥ grade 3. Five grade 5 AEs were reported of which four were unrelated to study drug and one was reported as possibly related due to bowel perforation. Eighteen patients (45%) achieved 12-week PFS with stable disease or better (confidence interval, 0.29-0.62;
CONCLUSIONS: This phase II study demonstrated clinical activity of cabozantinib in heavily pretreated, patients with refractory mCRC, and supports further investigation.
SIGNIFICANCE: Targeting angiogenesis through VEGF axis blockade provides incremental survival benefit in patients with mCRC. The hepatocyte growth factor/MET signal transduction pathway has been observed as a mechanism for acquired resistance. Dual inhibition of VEGF plus MET is an attractive therapeutic strategy. This phase II trial demonstrated clinical activity with cabozantinib, a multi-TKI targeting VEGFR2 and MET, in patients with refractory, mCRC.
Clinical Institute
Cancer
Clinical Institute
Digestive Health
Department
Gastroenterology
Department
Oncology
Recommended Citation
Scott, Aaron J; Basu Mallick, Atrayee; Dotan, Efrat; Cohen, Steven J; Gold, Philip J; Hochster, Howard S; Subramaniam, Somasundaram; Barzi, Afsaneh; Watts, George S; Blatchford, Patrick J; and Messersmith, Wells A, "A Phase II Study Investigating Cabozantinib in Patients with Refractory Metastatic Colorectal Cancer (AGICC 17CRC01)." (2022). Articles, Abstracts, and Reports. 7268.
https://digitalcommons.providence.org/publications/7268
