2214 - A Phase II Study of Fruquintinib Combined with Tislelizumab and Sequential Radiotherapy for Recurrent or Oligoprogressive Esophageal Squamous Cell Carcinoma

Purpose/Objective(s): Therapeutic options are limited for patients with esophageal squamous cell carcinoma (ESCC) experiencing recurrence or oligoprogression after first-line therapy. This single-arm, open-label phase II study evaluated the efficacy and safety of fruquintinib (a vascular endothelial growth factor receptor tyrosine kinase inhibitor) combined with tislelizumab (an anti-PD-1 antibody) followed by sequential radiotherapy.

Materials/Methods: Eligible patients had histologically confirmed ESCC with recurrence or oligoprogression (less than or equal to 5 lesions/3 organs) after at least one prior line of therapy. Patients received induction therapy with oral fruquintinib (3-5 mg/day, 2 weeks on/1 week off) plus intravenous tislelizumab (200 mg, every 3 weeks) for 2-4 cycles. Those without disease progression then received sequential radiotherapy (50 Gy/25 fractions to locoregional sites or stereotactic body radiotherapy to oligometastases). Maintenance therapy with fruquintinib and/or tislelizumab continued until progression or intolerance. The primary endpoint was progression-free survival (PFS). Secondary endpoints included objective response rate (ORR), disease control rate (DCR), overall survival (OS), and safety.

Results: Between January 2023 and September 2024, 43 patients were enrolled, and 28 who completed induction therapy were analyzed. The median age was 64 years. With a median follow-up of 32.4 months, the median PFS was 11.4 months (95% CI: 7.51-15.29), and the median OS was 24.0 months (95% CI: 11.87-36.13). The ORR was 71.4%, and the DCR was 89.3%. Multivariate analysis identified the pan-immune-inflammation value (PIIV) after treatment as an independent prognostic factor for both PFS (HR=3.937, p=0.004) and OS (HR=10.526, p=0.002). The treatment regimen was tolerable, with most adverse events being grade 1-2. Common grade 1-2 toxicities included decreased appetite (82.1%), hypertension (60.7%), and fatigue (53.6%).

Conclusion: The combination of fruquintinib, tislelizumab, and sequential radiotherapy demonstrated promising efficacy and manageable toxicity in patients with recurrent or oligoprogressive ESCC. A lower PIIV during and after treatment independently predicted longer survival, highlighting its potential as a robust prognostic biomarker and warranting further validation in randomized controlled trials.