In patients with chemo-refractory metastatic colorectal cancer (mCRC), trifluridine/tipiracil (FTD/TPI) with or without bevacizumab demonstrated a significant and clinically relevant improvement in survival compared with FTD/TPI monotherapy, with a favorable safety profile. The findings were presented at the ESMO 21st World Congress on Gastrointestinal Cancer.

FTD/TPI, also known as TAS-102, demonstrated prolonged survival in patients with chemo-refractory mCRC in the C-TASK FORCE trial and a small phase 1/2 study.

Inspired by these promising results, a Danish team of researchers designed an investigator-initiated randomized trial to compare outcomes of FTD/TPI treatment with or without bevacizumab. The study data were presented by Per Pfeiffer, MD, PhD, Department of Oncology, Odense University Hospital, Odense, Denmark.

The study enrolled 93 patients with histologically confirmed and chemo-refractory mCRC. Inclusion criteria included disease progression during or after therapy with fluoropyrimidine, irinotecan, and oxaliplatin; failure of EGFR-inhibitor treatment (RAS wild-type patients), with or without bevacizumab treatment; and PS 0-1. FTD/TPI was administered orally at the dose of 35 mg/m2/dose bid from days 1 to 5 and 8 to 12 in the first arm, and the same dose of FTD/TPI was combined with bevacizumab at a dose of 5 mg/kg on day 1 and on day 15 of a 28-day treatment cycle in the second arm.

A total of 80 patients were needed to show an increase in progression-free survival (PFS) from 1.8 months to 3.8 months. A planned safety analysis was performed once 40 patients had received 2 cycles of therapy, and no toxicity issues were seen. At that time, PFS was slightly longer than expected in the FTD/TPI only arm.

Dr Pfeiffer reported the efficacy and safety data of all 93 patients (intention-to-treat population) that were randomized from September 2017 to October 2018. He and his coinvestigators found that median PFS was significantly improved in the arm that received FTD/TPI plus bevacizumab (n = 46; 4.6 months) compared with the arm that received FTD/TPI alone (n = 47; 2.6 months; hazard ratio [HR], 0.45; 95% CI: 0.29, 0.72; P <.001). In addition, the median overall survival (OS) was significantly prolonged with FTD/TPI plus bevacizumab vs FTD/TPI alone (9.4 months vs 6.7 months, respectively; HR, 0.55; 95% CI: 0.32, 0.94; P <.03). After a median follow-up for OS of 11 months, 37 patients were alive as of February 15, 2019.

Patients in the FTD/TPI plus bevacizumab arm also completed a greater number of cycles of chemotherapy (4 vs 2) and had a longer therapy duration than their counterparts receiving FTD/TPI alone (median, 2.4 months vs 4.9 months, respectively).

Therapy was well-tolerated, and adverse events were as expected. Patients receiving FTD/TPI plus bevacizumab had more grade 3-4 neutropenia (67% vs 38% for FTD/TPI alone, P <.05), and 3 patients had febrile neutropenia with FTD/TPI plus bevacizumab versus 1 with FTD/TPI alone. Serious adverse events were observed in 21 patients and 19 patients in the FTD/TPI plus bevacizumab and FTD/TPI-alone arms, respectively.

“This trial showed for the first time that addition of bevacizumab to [FTD/TPI] significantly prolonged PFS and OS, irrespective of prior bevacizumab treatment,” Dr Pfeiffer concluded. “The combination is a new option in patients with chemo-refractory colorectal cancer and could be practice-changing.”—Kara Rosania

Pfeiffer P, Yilmaz M, Möller S, et al. Bevacizumab improves efficacy of trifluridine/tipiracil (TAS-102) in patients with chemorefractory metastatic colorectal cancer: a Danish randomized trial.

This article is a news release from ESMO 21st World Congress on Gastrointestinal Cancer Meeting. Read the original here.