Abstract
Both fruquintinib and TAS-102 monotherapies are guideline-recommended for third-line treatment of metastatic colorectal cancer (mCRC). This study aimed to analyze the preliminary outcomes of fruquintinib combined with TAS-102, with or without stereotactic body radiation therapy (SBRT), as a third- or later-line therapy for mCRC. This prospective, two-arm, phase II study planned to enroll 66 patients with mCRC who were unresponsive to at least two prior lines of therapy. Patients were allocated to either the FTS (fruquintinib + TAS-102 + SBRT) or FT (fruquintinib + TAS-102) group. Eligible patients received fruquintinib (4 mg, qd, days 1-21) and TAS-102 (30 mg/m(2), bid, days 1-5; 15-19) orally every 4 weeks until disease progression or intolerable toxicity. The primary endpoint was progression-free survival (PFS, per RECIST 1.1); secondary endpoints included overall survival (OS), objective response rate (ORR), disease control rate (DCR), and adverse events (AEs, graded using CTCAE v5.0). By January 20, 2025, 40 patients were enrolled (FTS group, 11; FT group, 29), with a median follow-up of 8.48 months. In 20 (50%) patients, the number of metastatic organs was ≥ 3. However, the number of metastatic lesions was > 5 in 32 (80%) patients. For the 36 eligible patients, the ORR and DCR were 19.4% and 88.9%, respectively. The median PFS was 8.58 months; however, the median OS has not been attained. The most common treatment-related AE was decreased white blood cell count (92.5%); grade 3-4 AEs included decreased lymphocyte count (12.5%). No treatment-related death occurred. Fruquintinib combined with TAS-102, with or without SBRT, showed promising preliminary efficacy and acceptable safety as third- or later-line treatment of mCRC.