Tislelizumab plus short-course chemo-radiotherapy for conversion therapy of unresectable ESCC (LATE): A proof-of-concept, phase Ib trial.

Abstract

e16119 Background: The standard of care for unresectable locally advanced esophageal squamous cell carcinoma (ESCC) is definitive chemoradiation (dCRT). However, long-term prognosis for patients(pts) receiving dCRT remains unfavorable. Our previous study adopting neoadjuvant short course chemo-radiotherapy in combination with ICIs (ICRT) showed promising locally control efficacy in locally advanced ESCC. Here we report the safety and antitumor activity of short course ICRT as conversion therapy for pts with unresectable ESCC. Methods: Pts with unresectable primary tumor site (invades adjacent organs such as trachea, bronchus, and aorta) and/or with unresectable regional lymph nodes or metastatic sites limited to non-regional lymph nodes (supraclavicular or abdominal lymph nodes outside the 3-field lymphadenectomy scope) ESCC were eligible for inclusion. Tislelizumab (200mg) was given with paclitaxel (135 mg/m2) and carboplatin (AUC = 5) on D1, D22. Short course radiotherapy (30Gy in 12 fractions on 5 days per week) was administered following the completion of immunochemotherapy. Target volumes were delineated after deliberations among radiation oncologists and surgeons. Lymph nodes outside the extended two-field lymph node dissection area were boosted to a radiation dose of 45Gy in 18 fractions. A third dose of tislelizumab and following esophagectomy were given at 3 and over 8 weeks after the completion of conversion radiotherapy, respectively. Target total enrollment was 30 pts. The primary endpoint was treatment safety. The secondary outcomes including conversion esophagectomy rate, pathological responses and patient survival. Results: From May 27th, 2022 to Jan 20, 2025, 30 pts were included in the trial. The median age was 63 years. 12 (40%) had supraclavicular lymph node metastasis; 13 (43.3%) with borderline resectable T4a or unresctable T4b disease; 16 (53.3%) had stage IVa while 14 (46.7%) had stage IVb disease. Common grade 3 and above AEs included leukopenia (n = 13), neutropenia (n = 13), heart injury (n = 2) and thrombocytopenia (n = 2). Among the 30 pts , 19 underwent R0 resection; 3 were still waiting for surgery. Reasons for not undergoing surgery were disease progression (n = 4), ICIs related grade 5 and 4 heart injury (n = 2), patients’ choice (n = 1) and tuberculosis reactivation (n = 1). Six pts with Grade III surgical complications were observed during the perioperative period. No postoperative death occurred. 9/19 (47.4%) complete pathological responses (ypT0N0) were observed. With a median follow-up time of 16.8 months (range: 12.5–21.1), 12-months progression free survival for pts who underwent surgery were 60.1% (95% CI: 34.8%,86.3%). Conclusions: Conversion short course chemo-radiotherapy in combination with ICIs followed by surgery was a promising treatment strategy for unresectable ESCC. Clinical trial information: NCT05394415 .