Fruquintinib combined with tislelizumab and SBRT as a later-line therapy in microsatellite stability (MSS) metastatic colorectal cancer (mCRC): Results from the FRUIT trial.

Abstract

150 Background: MSS patients (pts) account for the majority of all CRC pts and show poor response to immunotherapy. While fruquintinib plus PD-1 inhibitors is an effective option for MSS CRC pts in China who are refractory to multiple lines of therapy. In addition, immunomodulatory effects of stereotatic body radiotherapy (SBRT) have demonstrated in previous studies. Here, we report FRUIT trial of fruquintinib combined with tislelizumab and SBRT as a later-line therapy in MSS mCRC pts. Methods: In this single-arm, open-label, single-center, phase II trial (NCT04924179), we included mCRC pts who have failed with at least second-line therapy. Eligible pts undergo the following regimens on a 21-days cycle: fruquinitib (5mg, QD, PO, d1-14) plus tislelizumab (200mg, d1, I.V.) and SBRT (8-10Gy×5F, QOD). The primary endpoint is progression-free survival (PFS), and secondary endpoints are disease-control rate (DCR), objective response rate (ORR), overall survival (OS), and safety. The responses are evaluated according to RECIST Version 1.1 and adverse events are evaluated by CTCAE v5.0. Results: AS of August 31, 2022, 24 pts were included in the trial and 23 (11 male; media age 60 years; all pts with MSS; 7 had received 3 prior lines of therapy) in the efficacy analysis. 87%, 9% and 17% pts had received bevacizumab, regorafenib and cetuximab in previous therapy, respectively. Among 23 pts, median follow-up was 7.8 mo (95%CI: 4.31, 11.29). The median PFS was 5.1mo (95%CI: 0.57-9.63), with 9 pts still on treatment at data cutoff. 6pts achieved partial response (PR), 13 stable disease (SD), illustrating an ORR of 26% and a DCR of 83%. Adverse events (AEs) occurred in 22 (96%) pts which were mostly grade 1/2. 17% pts experienced a grade 3/4 AEs, including hypertension (9%), hand foot skin reaction (4%) and thrombocytopenia (4%). The combination regimen was well tolerate. Conclusions: Fruquintinib plus tislelizumab and SBRT as a later-line therapy in refractory MSS mCRC pts shows a promising clinical benefit, with a manageable safety profile, which suggests a potential new paradigm for therapy in MSS mCRC pts. Clinical trial information: NCT04924179 .