2062 - Medium Dose of TPF Chemotherapy with Concurrent Radiotherapy and Immunotherapy for Locally Advanced Esophageal Squamous Cell Carcinoma:A Prospective, Single Arm, Phase II Study (FUTURE-2)

Purpose/Objective(s):

Sintilimab is a PD-1 inhibitor, approved for the treatment of advanced esophageal squamous cell carcinoma (ESCC), but its efficacy in locally advanced disease is unclear. Combined with induction and consolidation Sintilimab, we aim to enhance efficacy and reduce toxicity by adding chemotherapy drugs while simultaneously lowering medication doses.

Materials/Methods:

FUTURE-2 was a prospective, single arm, phase II study done at Fudan University Shanghai Cancer Center. Patients with ESCC, aged 18-80 years, untreated, stage II-IVB except for hematogenous metastasis, adequate organ and bone marrow function were eligible for inclusion. Patients received one cycle of induction treatment with chemotherapy (TPF: paclitaxel, 60mg/m²; cisplatin, 30mg/m²; fluorouracil, 1000mg/m² ,civ 24h; q3w) and immunotherapy (Sintilimab, 200mg), and concurrent chemoradiotherapy (61.6Gy/28f for PTV-G and 50.4Gy/28f for PTV-C, TPF for two cycles) 3 weeks later. One cycle of consolidation chemotherapy and immunotherapy 1 month after radiotherapy, and then immunotherapy maintenance monthly for 1 year. The primary endpoint was progression free survival (PFS) at 1 year. The trial was registered with ClinicalTrials.gov, NCT06401447.

Results:

Between Dec 21, 2023, and Jul 10, 2025, 50 patients were enrolled. The median age was 65 years (range 46-79), 36 (72%) patients were male, and 26 (52%) patients had stage IVB disease, due to lymph node metastasis outside the region. All patients completed radiotherapy, and 48 (96.0%) patients received at least one cycle of concurrent chemotherapy, 44 patients (88%) received immuno-maintenance as plane. After a median follow up of 14 (range 6-25) months, 1-year PFS and overall survival (OS) was 70.0% and 85.0% respectively for all patients, 84.5%, and 94.7% respectively for patients with stage II-IVA, and 45.6%, and 76.2% respectively for patients with stage IVB. Three weeks after the first induction treatment, 48 patients underwent magnetic resonance assessment: 4 (8.0%) patients achieved complete remission, 17 (34.0%) patients with lesion regression exceeding 30%, 27 (54%) patients with lesion regression exceeding 20%, 34 (68%) patients with lesion regression exceeding 10%, and 6 (10.4%) patients with lesion enlargement. One year PFS for patients with lesion regression exceeding 30%, 20%, 10%, or not, was 100% and 47.4% (p=0.001),95.2% and 31.3% (p=0.000), 82.7% and 26.8% (p=0.001), respectively. No patients experienced treatment-related deaths. Grade 3 or worse adverse events were lymphopenia (41 [84%] ), neutropenia (12 [24%] ), leukopenia (9 [18%] ), esophagitis (5 [10%] ), respectively. Ten (20%) patients underwent immunogenic pneumonia of grade 1, and 1 (2%) patients of grade 2.

Conclusion:

Combining Sintilimab with medium dose of TPF chemotherapy and concurrent radiotherapy provided encouraging activity and tolerance for patients with locally advanced ESCC, and this regimen warrants further investigation.