2964 - Combining Avelumab with Platinum/5-Fluorouracil and Radical Hypofractionated Radiotherapy for Newly Diagnosed Metastatic Esophageal Squamous Cell Carcinoma: A Phase II Prospective Trial

J. C. H. Cheng¹, F. M. Hsu², T. C. Huang³, J. C. Guo⁴, and C. H. Hsu⁵; ¹Division of Radiation Oncology, Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan, ²Department of Radiation Oncology, National Taiwan University Cancer Center, Taipei, Taiwan, ³Graduate Institute of Oncology, National Taiwan University College of Medicine, Taipei, Taiwan, ⁴Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan, ⁵National Taiwan University Cancer Center, Taipei, Taiwan

Purpose/Objective(s): Metastatic esophageal squamous cell carcinoma (MESCC) poses a significant treatment challenge, with limited responses to conventional chemotherapy. Emerging evidence suggests the promising efficacy of incorporating immune checkpoint inhibitors into standard chemotherapy. Furthermore, studies suggested radiotherapy (RT) might improve the outcomes for patients with MESCC, and preclinical research also demonstrated RT potentially modulates anti-tumor immune response. This study explores the efficacy and safety of integrating Avelumab (Ave) with platinum/5-fluorouracil (PF) chemotherapy and radical hypofractionated radiotherapy (CRT) in treating MESCC, hypothesizing the synergistic and abscopal effects that could translate to clinical benefits. Materials/

Methods: In this prospective phase II trial, patients with biopsy-proven non-T4 MESCC, satisfactory performance status, and adequate organ function were eligible. The protocol systemic therapy regimen consisted of cisplatin or carboplatin plus 5-fluorouracil administered every 4 weeks for up to six cycles, alongside Avelumab (10 mg/kg) biweekly. Radiotherapy was delivered to the primary tumor and adjacent metastatic nodes with a total dose of 45 Gy in 15 fractions. Treatment efficacy was evaluated using RECIST 1.1 and iRECIST, while adverse events were assessed via CTCAE. The primary endpoint was the overall radiographic response rate at 6 months after treatment starts, with survival outcomes analyzed using the Kaplan-Meier method.
Results: From 2019 to 2022, 33 patients were screened and 26 were enrolled to receive the protocol treatment. The study cohort predominantly featured male participants (92%) with the most common metastasis sites being bone (73%), followed by lung and liver (each 65%), and distant nodes (54%). Most patients (77%) had oligo-metastatic disease (metastatic number < 5). All patients completed RT while 15 (58%) received = 5 cycles of protocol systemic therapy. Only two patients halted Ave use due to grade 3 immune-related adverse events. At 6 months, 20 patients were eligible for response evaluation and the radiographic response rate was 75% (95% confidence interval 54%–96%). The median overall survival was 13.3 months (95% confidence interval 9.1–17.5 months) while the median progress-free survival was 6 months (95% confidence interval 3.3–8.7 months). At the last follow-up, 4 patients remained alive and progression-free for more than 30 months after protocol treatment.
Conclusion: The initial findings indicate that Ave-PF-CRT is a feasible and potentially effective treatment for MESCC, with manageable toxicity, acceptable compliance, and clinical benefits. Notably, a subset of MESCC patients could achieve long-term disease control after Ave-PF-CRT. This approach warrants further validation in larger cohorts to confirm its efficacy and safety.