First-line trifluridine/tipiracil plus bevacizumab for unresectable metastatic colorectal cancer: SOLSTICE study design

Trifluridine/tipiracil (TT) is an orally administered combination of the thymidine-based nucleoside analogue trifluridine and the thymidine phosphorylase inhibitor tipiracil hydrochloride, which increases the bioavailability of cytotoxic trifluridine. Encouraging antitumor activity of first-line TT + bevacizumab (TT-B) has been observed in a Phase II study in patients with unresectable metastatic colorectal cancer ineligible for combination oxaliplatin- or irinotecan-based therapy. Here, we describe the design of SOLSTICE (NCT03869892), an open-label, Phase III trial in unresectable metastatic colorectal cancer patients who are not candidates for, or do not require, intensive therapy. The 854 patients were randomized 1:1 to receive first-line TT-B versus capecitabine + bevacizumab. The primary objective is to demonstrate superior progression-free survival with TT-B over capecitabine + bevacizumab. The first patient was enrolled in March 2019. Lay abstract Trifluridine/tipiracil is an oral chemotherapy drug combination that acts by affecting the DNA of tumor cells. In a previous study, initial (first-line) treatment with trifluridine/tipiracil plus the tumor-starving (anti-angiogenic) drug bevacizumab was effective in patients with metastatic colorectal cancer that could not be surgically removed (i.e., was unresectable) and who could not receive intensive therapy. The SOLSTICE trial is designed to compare the efficacy and safety of first-line trifluridine/tipiracil + bevacizumab versus another treatment, capecitabine + bevacizumab, in patients with unresectable metastatic colorectal cancer who are not candidates for intensive therapy.