Induction DCF plus nivolumab versus induction DCF for unresectable locally advanced esophageal squamous cell carcinoma.

Abstract

316 Background: Definitive chemoradiotherapy (dCRT) is the standard for unresectable locally advanced esophageal squamous cell carcinoma (LA-ESCC), but prognosis remains poor, with median survival about 13 months and 20% fistula rate. In the COSMOS trial, induction chemotherapy with docetaxel, cisplatin, and 5-fluorouracil (IC-DCF) followed by conversion surgery showed promising results, and JCOG1510 is evaluating this approach versus dCRT. Neoadjuvant DCF plus nivolumab (DCF+Nivo) demonstrated efficacy in resectable disease in the phase I study, and IC-DCF+Nivo showed short-term benefit in retrospective analysis, but no direct comparison with IC-DCF exists. Methods: We retrospectively analyzed patients with unresectable LA-ESCC treated at our institution with IC-DCF+Nivo (March 2023-May 2025) or IC-DCF (January 2014-December 2021). Regimen: docetaxel 70 mg/m² and cisplatin 70 mg/m² on day 1, and 5-fluorouracil 750 mg/m² on days 1–5; nivolumab 240 mg/body added on day 1 in IC-DCF+Nivo. Treatment was every 3 weeks for 3 cycles. The rates of conversion surgery, R0 resection, pathological complete response (pCR), clinical complete response (cCR) after dCRT, progression-free survival (PFS), objective response rate (ORR), and safety (CTCAE v5.0) were evaluated. Results: In total, 104 patients were analyzed: 45 with IC-DCF+Nivo and 59 with IC-DCF. Median follow-up was 9.0 vs 58.4 months. Median age was 64/65 years, and 71/75% were male. Performance status 0/1 was 47/53% vs 59/41%. Clinical T3/4b disease was 44/55% and 46/45%. Stage III/IVA/IVB was 36/29/36% and 25/51/24%. Tracheal invasion was the main unresectable factor (60% vs 61%). Three cycles were completed in 78% vs 92%. In IC-DCF, discontinuation was only for PD; in IC-DCF+Nivo, 16% for adverse events, none clearly due to nivolumab. Radical surgery was feasible in 56% vs 54%, and R0 resection was achieved in 54% vs 46%. pCR occurred in 13% vs 10%. dCRT without surgery was chosen in 0 vs 7%, with no cCR. ORR was 88% vs 23% (p<0.01), DCR 98% vs 96%. IC-DCF+Nivo achieved longer PFS of 16.5 months compared to 10.6 months for IC-DCF (HR 0.96, 95% CI 0.54-1.72, p=0.89). Grade 3–4 neutropenia occurred in 46/53%, anorexia in 5/4%, febrile neutropenia in 3/9%, and fistula in 2/4%. Conclusions: IC-DCF+Nivo showed better tumor shrinkage and PFS with comparable safety to IC-DCF, suggesting it may be a promising option.