Abstract 194P
Background
Treatment landscape is challenging for patients with advanced esophageal squamous-cell carcinoma (ESCC) who have failed first-line immunotherapy. The potential of combining antiangiogenic therapy with chemotherapy in the treatment of esophageal cancer is well established. Therefore, this study aims to assess the efficacy and safety of combining fruquintinib with S-1 in treating advanced ESCC patients following first-line immunotherapy failure.
Methods
This phase II, single-arm, prospective study consists of dose-finding and dose-expansion phases. The dose-finding phase follows a 3+3 design. Patients received oral fruquintinib (3 mg, 4 mg, 5 mg, d1-d14, q3w) starting at 4 mg qd, in combination with S-1 (40 mg, 50 mg, or 60 mg based on body surface area, bid, d1-d14, q3w) until unacceptable toxicities, progressive disease, or death. The primary endpoint was progression-free survival (PFS). Secondary endpoints included the recommended phase II dose (RP2D), overall response rate (ORR), disease control rate (DCR), and overall survival (OS).
Results
As of June 20th, 2024, ten patients were enrolled in the dose-finding phase and 9 were evaluable, among whom 6 were from fruquintinib 4 mg cohort and 3 from 5 mg cohort. Dose-limiting toxicities (DLTs) were observed in 2 patients at the 5 mg dose level, while no DLTs occurred at 4 mg dose level, and the RP2D was determined. The most common treatment-related adverse events (TRAEs) of any grade were fatigue (8/9), hypertension (4/9), diarrhea (4/9), mucositis (4/9) and abdominal pain (4/9). The most common grade 3 TRAEs were fatigue (3/9) and hypertension (3/9). No grade 4 TRAEs or SAEs were observed. Among the evaluable patients, 1 out of 6 patients from 4 mg cohort and 2 out of 3 patients from 5 mg cohort achieved partial response (PR), yielding an ORR of 33.3% (3/9). The DCR reached 100% (9/9). The median PFS was 5.4 months (95% CI: 2.1 - 10.8), while the median OS reached 10.8 months (95% CI: 2.1 - NA). This trial is still ongoing.
Conclusions
Fruquintinib 4 mg d1-d14, q3w in combination with S-1 was generally well tolerated with potential efficacy in ESCC patients after immunotherapy failure.
Clinical trial identification
NCT05636150.
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.