Chemo-immunotherapy sequential with radiotherapy and immunotherapy consolidation in patients with advanced or metastatic esophageal squamous cell carcinoma.

Abstract

342 Background: This study was to evaluate the efficacy and safety of chemo-immunotherapy combined with residual lesions irradiation of advanced stage esophageal squamous cell carcinoma. Methods: This is a single-arm, three-center, open-label study involving treatment-naïve patients with radiologically and histologically confirmed advanced or metastatic squamous-cell esophageal carcinoma. Enrolled patients were treated by induction chemo-immunotherapy, residual esophageal tumor irradiation and immunotherapy consolidation. In the induction phase, four cycles of docetaxel , cisplatin, and sintilimab were initiated. Patients with stable disease (SD) or partial response (PR) after induction therapy were subsequently received 50 Gy of radiation in 25 fractions for residual tumors. Maintenance sintilimab therapy was administered every 21 days for up to 31 cycles or until disease progression or intolerable toxicity occurred. Results: A total of 51 patients were enrolled in this study, of which 45 were evaluable for efficacy. All 51 patients were evaluable for toxicity for they had had at least one dose of chemo-immunotherapy. All participants were male, and all had histologically confirmed squamous-cell carcinoma. Among these, 14 (27.5%) were in stage III and 37 (72.5%) were in stage IV. The complete response (CR) rate was 6.7% (3/45), the partial response (PR) rate was 55.6% (25/45), and the disease control rate (DCR) was 88.9% (40/45) after chemo-immunotherapy. The median depth of response (DpR) was 33.0% for chemo-immunotherapy and was 53.0% after additional radiotherapy. The progression-free survival (PFS) was 16.4 months and the overall survival (OS) 29.25 months. The most common grade 3 or higher adverse event was neutropenia, occurring in 11.8% (6/51) patients. Conclusions: Chemo-immunotherapy followed by radiotherapy for residual tumors and maintenance sintilimab, demonstrated high response rates, prolonged PFS and OS as a first-line treatment for patients with advanced or metastatic esophageal squamous-cell carcinoma. Clinical trial information: NCT06138028 . Clinicopathological features and patient factors and summary of efficiency measures after chemo-immunotherapy (n=45) (%). Clinicopathological features and patient factors Factors No. of patients (n=51) (%) Gender  Male 51 (100.0)  Female 0 (0) Age (year)  < 65 27 (52.9)  ≥ 65 24 (47.1) PD-L1 (CPS)  < 5 11 (21.6)  ≥ 5 22 (43.1) Unknown 18 (35.3) ECOG PS  0 10 (19.6)  I 41(80.4) Clinical Stage  III 14 (27.5)  IV 37 (72.5) Metastatic Pattern  Regional lymph node 13 (25.5)  Cervical & Supraclavicular 17 (33.3)  Peritoneal lymph nodes 15 (29.4)  Lung 6 (11.8) Summary of efficiency measures after chemo-immunotherapy (n=45) (%) CR PR SD PD ITT 3 (6.7) 25 (55.5) 12 (26.7) 5 (11.1) PD-L1 < 5 0 (0) 6 (54.5) 3 (27.3) 2 (18.2) PD-L1 ≥ 5 2 (9.1) 11 (50.0) 7 (31.8) 2 (9.1) PD-L1 Unknown 1 (5.0) 12 (60.0) 5 (25.0) 2 (10.0) Stage III 2 (15.4) 6 (46.1) 3 (23.1) 2 (15.4) Stage IV 1 (3.1) 19 (59.4) 9 (28.1) 3 (9.4)