Efficacy and safety of fruquintinib plus trifluridine/tipiracil (TAS-102) as third-line treatment in patients with metastatic colorectal adenocarcinoma: Results from a single arm, phase 2, multicenter study.

3536 Background: Fruquintinib and TAS-102 are two standard therapies for patients (pts) with previous-treated metastatic colorectal adenocarcinoma (mCRC) worldwide. SUNLIGHT trial demonstrated improvement in progression-free survival (PFS) and overall survival (OS) of TAS-102 plus bevacizumab compared with TAS-102 alone. In this study, we aim to evaluate the efficacy and safety of fruquintinib plus TAS-102 as third-line treatment for mCRC pts. Methods: In this open-label, single-arm, multicenter, phase 2 trial (NCT05004831), pts with mCRC who had failed at least two prior standard treatment regimens were enrolled. Eligible pts received fruquintinib (4mg, qd, d1-21) and TAS-102 (35mg/m 2 , bid, d1-5, 8-12) orally every 4 weeks until disease progression or unacceptable toxicity. Primary endpoint was PFS (per RECIST v1.1). Secondary endpoints were OS, objective response rate (ORR), disease control rate (DCR) and safety (per NCI-CTCAE v5.0). Results: From Mar 2022 to Aug 2023, 50 eligible pts were enrolled. The median age was 60 years (range 39-76), male accounted for 58.0%. 82% pts were of left-sided colon and rectal cancer. 42.0% pts had RAS mutant and 58.0% had liver metastasis. Prior treatments and proportion were 5-FU 100%, anti-VEGF 88.0% and anti-EGFR 26.0%. As of Jan 10, 2024, 46 pts had at least one tumor assessment and 7 pts were still on treatment. 10.9% (5/46) pts achieved partial response (PR) and 63.0% (29/46) pts had stable disease (SD) as best response. The median PFS was 6.46 (95%Cl: 4.20-8.62) months (mo). The 6-mo, 9-mo and 12-mo PFS rates were 50.9%, 25.4% and 21.8%, respectively. The median PFS was 5.51 (95%Cl: 2.43-NA) mo, 5.84 (95%CI: 3.97-NA) mo and 6.59 (95%Cl: 4.79-NA) in RAS mutant pts (n=21), RAS wild-type pts (n=16), and RAS status unknown pts (n=13), respectively. The median PFS was comparable in liver metastasis (LM) and non-LM pts (6.59 95%CI: 4.07-8.62 mo vs. 6.46 95%CI: 3.74-NA mo, p=0.77). Median OS was not mature with 15.5 mo of median follow-up time. Treatment-related adverse events (TRAEs) were generally manageable and tolerable. The most common hematological TRAEs (any grade, grade 3-4) included neutrophil count decreased (80.0%, 52.0%), white blood cell count decreased (70.0%, 24.0%), and anemia (54.0%, 20.0%). Non-hematological TRAEs were mainly grade 1-2 including loss of appetite (22.0%), malaise (14.0%), abdominal pain (12.0%), diarrhea (12.0%) and vomiting (10.0%). A grade 3 hypertension was reported. No treatment-related deaths were observed. Conclusions: These preliminary results indicate that fruquintinib plus TAS-102 as third-line treatment in patients with mCRC was well tolerated with encouraging clinical activity. The enrollment is closed and more OS data will be presented in the future. Clinical trial information: NCT05004831 .