Safety and Tolerability of Neoadjuvant Radiotherapy Combined With Anti-PD-1 Antibody Toripalimab for Locally Advanced, Resectable Esophageal Squamous Cell Cancer: A Prospective Phase IB Trial.

<bold>Purpose/objective(s): </bold>To assess the safety and tolerability of neoadjuvant radiotherapy combined with toripalimab for locally advanced, resectable esophageal squamous cell cancer (ESCC).<bold>Materials/methods: </bold>A total of 22 patients with newly diagnosed locally advanced, resectable ESCC (clinical stage: T3-4N0M0/T1-4N+M0, according to the 8th AJCC stage system) were enrolled. Patients received neoadjuvant radiotherapy (NRT) with 41.4 Gy in 23 fractions by intensity modulated radiotherapy (IMRT) combined with 4 cycles (240mg, Q3W) of toripalimab. Surgery was performed within 7-8 weeks after completion of NRT. The primary endpoints are treatment-related adverse events (TRAEs). The second endpoints are pathological complete response (pCR) and objective response rate (ORR). ORR was evaluated after NRT according to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.0.<bold>Results: </bold>A total of 22 patients were enrolled between October 2019 to December 2020. 17 patients were male and 5 patients were female. The median age was 60 years (range, 48 to 70 years). 9 patients were in stage II and 13 patients were in stage III. All patients finished NRT as planned, 3 (13.6%) patients discontinued toripalimab treatment, one for progressive disease after 3 cycles of toripalimab, one for treatment-related AEs after 2 cycles and one for patient wishes after 2 cycles. 2 (9.1%) patients achieved complete response, 13 (59.1%) patients achieved partial response of which 1 patient had liver metastasis after 4 cycles of toripalimab, 6 (27.3%) patients remained stable disease, and 1 (4.5%) patient had progression disease. ORR was 68.2% (15/22), and disease control rate (DCR) was 95.5% (21/22). As of Feb. 26, 2021, 14 (63.6%) patients had received radical surgery, among them 7 (50.0%) experienced pCR of primary tumor and lymph nodes, 8 (57.1%) presented primary tumor pCR, and 9 (64.3%) had a major pathological response (MPR), 2 (9.1%) patients did not undergo surgery for progressive disease (1 patient of left supraclavicular lymph node metastasis and 1 patient of liver metastasis), and the remaining 6 patients still awaits radical surgery as scheduled. 15 (68.2%) patients experienced TRAEs. The common TRAEs were mild (grade 1 or 2) including leukopenia (n = 9), radiation esophagitis (n = 8) and aspartate transaminase (AST) elevation (n = 5), pruritus (n = 2), alanine transaminase (ALT) elevation (n = 1) and pneumonitis (n = 1). Only 1 (4.5%) patient developed grade 3 myocarditis, grade 3 AST elevation and grade 3 ALT elevation 2 weeks after NRT, improved after treatment with methylprednisolone, and is currently waiting for radical surgery.<bold>Conclusion: </bold>The trial showed that NRT plus toripalimab demonstrated a manageable safety profile and encouraging therapeutic effect in patients with locally advanced, resectable ESCC, which warrants additional investigations in larger cohorts. The trial was registered in Chictr.org.cn ((Registration Number: ChiCTR1900022282). [ABSTRACT FROM AUTHOR]