3092 - Phase II Study of Sintilimab Combined with Chemotherapy and Sequential Radiotherapy in First-Line Treatment of Oligometastatic Esophageal Cancer

L. Wang¹, B. Zou¹, B. Fan¹, A. Gao¹, W. Li¹, Y. Yu¹, W. Huang¹, X. Liu², and M. Gao¹; ¹Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China, ²Department of Medical Oncology, Linyi Cancer Hospital, Linyi, China

Purpose/Objective(s): Esophageal cancer has a high incidence and mortality rate, mainly in developing countries. Currently, immunotherapy combined with chemotherapy has been widely used in advanced and metastatic esophageal cancer, but most patients eventually develop disease progression. In previous studies, it was found that the addition of radiotherapy could have a synergistic effect with immunotherapy, thereby improving the efficacy. This study was to evaluate the efficacy and safety of sintilimab combined with chemotherapy and sequential radiotherapy in the treatment of patients with oligometastatic esophageal cancer. Materials/

Methods: This is a single-arm, multicenter, phase II study (ChiCTR2300071203). Patients with oligometastatic esophageal cancer will be enrolled after screening and receive sintilimab (200mg, d1, Q3W) combined with chemotherapy (conventional chemotherapy regimen, 4 cycles). Subjects who did not progress after chemotherapy continued to receive radiotherapy (for esophageal primary lesions, 1.8-2Gy/1f, DT=45Gy; for =1 oligometastatic lesions, =3Gy/1f, DT=30Gy). The patients continued to receive sintilimab monotherapy after radiotherapy. The primary endpoint was progression-free survival (PFS). Secondary endpoints included objective response rate (ORR),disease control rate (DCR), duration of response (DOR), overall survival (OS), and Treatment-related adverse events (TRAEs).
Results: From March 2021 to October 2023, a total of 35 subjects were enrolled,of which 31 patients could be evaluated. The median age was 61 years. All patients were male, with an Eastern Cooperative Oncology Group (ECOG) performance status of 1. 17 patients had smoking history. All cases were in stage IV, including 11 stage IVA and 20 stage IVB. The ORR was 87.1% (95% CI 71.2- 94.9), including 27 cases of PR, 4 cases of SD. The DCR was 100%. The median DOR was 15 months (95% CI 8.31-NA), and the median time to response was 1.5 months. The median PFS was 15.6 months (95% CI 7.39-18.5); 12-month and 18-month PFS rates were 59.2% and 32.4%, respectively. The median OS was 23.9 months (95% CI 18.5-NA); and the 12- and 24-month PFS rates were 94.7% and 49.8%, respectively. The overall incidence of TRAEs was 93.5% (29 cases), of which 29% were =3 grade, including neutropenia, leukopenia, aspartate aminotransferase increased, alanine aminotransferase increased, lymphopenia, hyponatremia, digestive tract hemorrhage. A total of 18 (58.1%) subjects had immune-related adverse events (irAEs). The incidence of pneumonia caused by radiotherapy or sintilimab was 22.6% (7 cases),and all of them were grade 1-2. 3 cases of TRAEs leading to discontinuation. No AE leading to death occurred.
Conclusion: In the first-line treatment of oligometastatic esophageal cancer, Sintilimab combined with chemotherapy and sequential radiotherapy demonstrated promising clinical activity and a manageable safety profile.