289 - Sequential Chemo-Immunotherapy as a Novel Bridging Strategy for Non-Complete Responders after Neoadjuvant Chemoradiotherapy in Esophageal Cancer: First Prospective Phase 2 Trial Challenging Immediate Surgery Paradigm
Presenter(s)
Q. Wang1, L. Peng2, C. Wang2, W. He3, L. Wu1, M. Lan1, J. Lang4, and Y. Han2; 1Department of Radiation Oncology, Sichuan Cancer Hospital and Institution, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Radiation Oncology Key Laboratory of Sichuan Province, Chengdu, China, 2Department of Thoracic Surgery, Sichuan Cancer Hospital& Institution, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China, 3Sichuan Clinical Research Center for Cancer,Sichuan Hospital Cancer & Institute, Sichuan Cancer Center, University of Electronic Science and Technology of China, Chengdu, China, 4Department of Radiation Oncology, Radiation Oncology Key Laboratory of Sichuan Province, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, University of Electronic Science and Technology of China, Chengdu, China
Purpose/Objective(s): Non-clinical complete responders (non-CCR) after neoadjuvant chemoradiotherapy (NCRT) for locally advanced esophageal squamous cell carcinoma (LA-ESCC) face high recurrence risks with immediate surgery. This first study evaluates the efficacy and safety of sequential chemo-immunotherapy (SCI) as a bridge to surgery in this population.
Materials/Methods: In this phase 2 cohort study (NCT05189730), 169 LA-ESCC patients who underwent NCRT were prospectively enrolled from June 2021 to January 2025. The NCRT regimen included paclitaxel and carboplatin every three weeks for two cycles. Concurrent radiotherapy (40–41.4 Gy over 4–5 weeks) was administered. Post-NCRT, patients were assessed for non-CCR and stratified into two groups: the SCI group received two additional cycles of chemotherapy and tislelizumab (200 mg intravenously every three weeks) before surgery, while the DS group proceeded to surgery immediately. The primary endpoint was pCR rate; secondary endpoints included major pathological response (MPR) rates and safety.
Results: Eighty-seven non-CCR pts were included (SCI: n = 54; DS: n = 33). The median age was 63 years, with 78.0% male patients. Most patients were stage IIIB(83.9%). Surgery rates were 85.2% in the SCI group (46/54) and 81.8% in the DS group (27/33). In the ITT population, SCI significantly improved pCR rates (40.7% [22/54] vs. 18.1% [6/33]; OR: 3.06, p = 0.024, , one-sided Fisher's Exact Test) and showed a trend toward higher MPR rates (51.8% [28/54] vs. 33.3% [11/33]; OR: 2.14, p = 0.071). In the PP population, pCR rates remained higher in SCI (47.8% [22/46] vs. 22.2% [6/27]; OR: 3.16, p = 0.026) and showed a trend toward higher MPR rates (60.9% [28/46] vs. 40.7% [11/27]; OR: 2.02, p = 0.078). At 12 months, PFS rates were 95.6% in the SCI group versus 77.3% in the DS group (p = 0.094) in the ITT population, and 97.4% versus 77.8% (p = 0.064) in the PP population. SCI-related adverse events included lymphopenia (97.7%), leukopenia (84.6%), and fatigue (50.0%). In the no-surgical patient in SCI group, three cases experienced immune pneumonitis and thyroid dysfunction, respectively. Treatment-related adverse events in the SCI group included lymphopenia (97.7%), leukopenia (84.6%), and fatigue (50.0%).The main postoperative complications in the SCI group and DS group were anastomotic leakage and recurrent laryngeal nerve injury (3/46 vs. 2/27, P = 0.629). No significant adverse events specific to treatment were reported in the SCI group.
Conclusion: This pioneering study demonstrates that SCI as a bridging strategy significantly improves pCR rates by > 2-fold and shows promising PFS trends with manageable toxicity in non-CCR LA-ESCC, challenging the immediate surgery paradigm. These results warrant validation in randomized phase 3 trials to redefine standard-of-care.