An organ-preserving strategy in patients with esophageal squamous cell carcinoma treated with immunochemotherapy.

424 Background: This study evaluated the strategy of dose-dense chemotherapy plus a PD-1 inhibitor with selective organ-preservation in patients with advanced esophageal squamous cell carcinoma (ESCC). Methods: Patients with locally advanced or metastatic (confined to the supraclavicular lymph nodes) ESCC were enrolled to receive treatment with a PD-1 inhibitor plus albumin bound-paclitaxel, cisplatin and 5-FU every two weeks. After six cycles of treatment, patients with clinical complete response (cCR) confirmed by computed tomography (CT), endoscopy and biopsy underwent an organ-preserving strategy with continuation of immunochemotherapy. The primary endpoint was cCR rate in the intention-to-treat population. A post hoc analysis was also conducted in patients with advanced ESCC who had a best response of CR after immunochemotherapy from three prospective studies we previously reported. Consecutive patients who had not received esophagectomy prior to immunochemotherapy, and had durable CR as confirmed by imaging, endoscopy with or without biopsy were identified to provide supporting evidence for the organ-preserving strategy. Results: A total of twenty patients were enrolled. At data cut-off (September 12, 2024), eight patients fulfilled the criteria of cCR (40%), while six patients actually adopted the organ-preserving strategy. 75% of the patients experienced ≥ grade 3 treatment-related adverse events (TRAEs), most commonly neutropenia and leukopenia. All TRAEs were managed with appropriate medical care. In the post hoc analysis, out of 71 patients who had a best response of CR to immunochemotherapy in three previous trials, sixteen consecutive patients who had not received esophagectomy before immunochemotherapy, and remained CR assessed with CT at data cut-off were identified. Although endoscopy was not mandatory during follow-up, twelve patients underwent endoscopic exams, and none of them had suspected tumor with endoscopic visualization. Biopsies were taken for eight patients, and were all negative for tumor. The median follow-up for these twelve patients reached 42.7 months, suggesting a long-term disease-free survival after immunochemotherapy. Conclusions: Dose-dense nab-paclitaxel, cisplatin and 5-FU combined with a PD-1 inhibitor showed encouraging cCR rate and manageable safety, making organ-preservation a possible subsequent approach in patients with advanced ESCC. Clinical trial information: ChiCTR2300072992.