The combination of PD-1 inhibitor with chemotherapy ± salvage chemoradiotherapy for local primary-recurrence esophageal squamous cell carcinoma after definitive chemoradiotherapy: A prospective, multicenter, single-arm clinical study (ESO-Nanjing12).

e16035 Background: The efficacy of programmed death receptor 1(PD-1) inhibitors combined with chemotherapy for advanced and metastatic ESCC has been recognized. However, there is limited evidence on the use of PD-1 inhibitors combined with chemotherapy for local Primary-recurrent ESCC after definitive chemoradiotherapy or radiotherapy, and further exploration is needed. Methods: This is a prospective clinical study. The study will focus on those who have attained a complete response (CR) subsequent to definitive chemoradiotherapy or radiotherapy and have a histologically proven in-field recurrence, with no distant metastases. These patients will receive treatment with a PD-1 inhibitor (sintilimab or camrelizumab 200mg, d1, q3w) combined with monotherapy chemotherapy (paclitaxel 175mg/m 2 or irinotecan 250mg/m 2 , d1, q3w) for 4 cycles, followed by a 2-year maintenance treatment with PD-1 inhibitors. During this period, patients diagnosed with esophageal wall thickening and identified as having progressive disease (PD) have the option to undergo salvage radiotherapy (45-50.4 Gy/25-28/F/5-5.5 weeks) in conjunction with a dual-agent chemotherapy (paclitaxel 50 mg/m 2 , d1 + carboplatin AUC 2, d1, qw) for 5 cycles. The primary endpoint of is after recurrence survival (ARS). The secondary endpoints include the progression-free survival (PFS) and safety. Results: From July 2023 to January 2025, a total of 35 patients were enrolled in the study. The median age was 65 years (range, 53-76 years). Among the enrolled patients, 27 completed a 4-cycle treatment regimen of PD-1 inhibitor combined with monotherapy chemotherapy, 14 patients are currently in the PD-1 inhibitor maintenance phase, and only 2 patients have received salvage chemoradiotherapy. To date, the disease control rate (DCR) is 65.7%(23/35). The median ARS and PFS were 27.3 months (95% CI : 9.7-44.8 months) and 15.0 months (95% CI : 4.9-21.2 months). The 1-year and 2-year ARS rates were 76.0% and 66.4%, respectively. Besides, the 1-year and 2-year PFS rates were 59.1% and 38.7%. In terms of safety, adverse events were mostly grade 1-2, with no severe adverse events occurring. The common adverse events included anemia(22 ; none with grade≥3), Leukopenia (12 ;4 with grade≥3), thrombocytopenia(9 ; 2 with grade≥3) and alopecia(9 ; none with grade≥3).The common immune-related adverse events were hypothyroidism(14 ; none with grade≥3) and elevated troponin T(12 ; none with grade≥3). Conclusions: The combination of PD-1 with chemotherapy for the treatment of locally primary-recurrent of ESCC following definitive chemoradiotherapy or radiotherapy represents a safe and efficacious therapeutic strategy. This approach not only improve ARS but also ensures safety and manageable outcomes.