Multi-institutional analysis of real-world activity and safety of trifluridine/tipiracil plus bevacizumab in patients with refractory metastatic colorectal cancer
Background
Trifluridine/tipiracil (TAS-102) plus bevacizumab (BEV) was compared with TAS-102 monotherapy in a randomized, open-label, phase 2 trial, and produced a statistically significant and clinically relevant improvement in progression-free survival (PFS) with tolerable toxicity in patients (pts) with refractory metastatic colorectal cancer (mCRC). An open-label, controlled two-arm, randomized phase 3 trial comparing the combination with single agent TAS-102 is currently ongoing. However, evidence supporting the role of TAS-102 plus BEV in a real-world setting is limited.
Methods
We conducted a retrospective, observational study of patients with mCRC refractory or intolerant to standard therapies. Patients were treated with TAS-102 35 mg/m2 twice daily on days 1–5 and 8–12 every 28 days plus BEV 5 mg/kg on days 1 and 15 at Oncology Department of Università degli Studi della Campania Luigi Vanvitelli and Oncology Unit of Hospital San Giuliano in Naples, IT. Previous therapy with fluoropyrimidines, irinotecan, oxaliplatin, bevacizumab, aflibercept, regorafenib and cetuximab or panitumumab (only RASwt) was allowed. Previous participation in clinical trials was allowed as well. Clinicopathological characteristics, Overall Response Rate (ORR) and Disease Control Rate (DCR), Overall Survival (OS) and Progression-Free Survival (PFS) and safety data were retrospectively collected and analyzed.
Results
We recorded 22 pts treated between December 2017 and March 2022. Median age was 69 years (range 30-82 years), 40% male, 100% ECOG PS0-1, 59% left-sided, 36% RASmt, 4% BRAFmt, 41% synchronous presentation, and 95% primary tumor resection. 54% of pts had liver metastases, 59% lung metastases, 27% peritoneal carcinomatosis. Median number of previous treatment lines was 2 (range 0-5). 86% of patients received at least one previous anti-angiogenic agent. ORR and DCR were 4% and 77%, respectively. With a median follow up of 12 months (range 3-39), median PFS was 8 months (95% CI, 5.1-10.9 months) and median OS was 14 months (95% CI, 10.2-17.8 months). Median PFS was longer in RAS/RAFwt patients (8 vs 5 months) and in patients without liver metastases (9 vs 5 months). 70% (12/17) of patients who discontinued treatment, eventually received 1 or more lines of subsequent therapy. Adverse events of any grade were reported in 77% (17/22) of patients. The most common grade 3-4 toxicities were: neutropenia (9%) and anemia (4%). 50% of patients required either dose delays or dose reductions due to toxicity. No treatment-related deaths occurred.
Conclusions
Our series provides further evidence on the activity and safety of TAS102 plus BEV combination in a real-world series of Western refractory mCRC patients.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosures
T. Troiani: Advisory / Consultancy: Roche, Merck-Serono, Sanofi; Speaker Bureau / Expert testimony: Servier, Novartis, Bayer. All other authors have declared no conflicts of interest.
