Published online Apr 15, 2021. doi: 10.4251/wjgo.v13.i4.295
Peer-review started: December 28, 2020
First decision: January 17, 2021
Revised: January 28, 2021
Accepted: March 11, 2021
Article in press: March 11, 2021
Published online: April 15, 2021
Angiogenesis inhibitors (AIs) combination with cytotoxic chemotherapy is a promising treatment for patients with colorectal cancer (CRC). Aflibercept (AFL) is an option for second-line treatment of CRC, according to the ‘VELOUR’ trial. Currently, we can choose from three AIs, including bevacizumab, ramucirumab, and AFL. Different AIs can be used in subsequent treatment because of their distinctive mechanisms of action. We addressed the uncertainty regarding AFL efficacy and safety in heavily-treated patients by comparing outcomes of survival treatment with second-line treatment.
To determine and compare the efficacy and safety profiles of AFL in the second-line and salvage therapy settings.
Clinical data of 41 patients with advanced CRC who received intravenous AFL combined with the folinic acid-fluorouracil-irinotecan (FOLFIRI) regimen were collected retrospectively from six institutions in Japan, for the period from May 2017 to March 2019. Patient characteristics collected included age, sex, tumor location, RAS and RAF status, metastatic sites, number of previous treatment cycles, therapeutic response, adverse events, duration of previous AI treatment, and survival time. The end points were time to AFL treatment failure (aTTF) and median survival time post-AFL (aMST). Statistical analyses were performed to compare the efficacy and safety in the second-line setting with those of the salvage therapy setting, which was defined as the days since the end of second-line therapy.
All 41 patients who received AFL + FOLFIRI for advanced CRC had metastatic or unresectable cancer. Twenty-two patients received AFL in the second-line setting and nineteen in the salvage therapy setting. The patient characteristics were similar in the two groups, except for two factors. The median duration of the previous AI administration was shorter in the second-line patients compared with that in the salvage therapy patients (144 d vs 323 d, P = 0.006). In the second-line and salvage therapy groups, the objective response rates were 11% and 0%, respectively (P = 0.50), and the disease control rates were 53% and 50%, respectively (P = 1.00). In the second-line and salvage therapy groups, the aTTF (123 d vs 71 d, respectively), aMST (673 d vs 396 d, respectively), and incidence of adverse events of grade 3 [8 (36%) vs 9 (47%)] were not significantly different between the two groups.
AFL can be used to treat advanced CRC patients, with a similar safety and efficacy in the salvage therapy setting as in the second-line setting.
Core Tip: We compared the efficacy and safety of aflibercept plus the folinic acid-fluorouracil-irinotecan regimen as salvage treatment with those of second-line treatment in patients with advanced colorectal cancer. In the second-line and salvage therapy settings, the objective response rates were 11% and 0%, respectively (P = 0.50). The disease control rates, times to aflibercept treatment failure, median survival times post-aflibercept, and incidences of adverse effects greater than or equal to grade 3 were similar in the two groups. Aflibercept could be safe and confer a survival benefit in patients with advanced colorectal cancer, regardless of the number of treatment lines.