Short-term outcomes of induction FLOT plus nivolumab for unresectable locally advanced esophageal squamous cell carcinoma in cisplatin-unfit patients.

Abstract

319 Background: Definitive chemoradiotherapy (dCRT) remains the standard of care for unresectable locally advanced esophageal squamous cell carcinoma (LA-ESCC). However, the median survival is about 13 months and fistula formation occurs in 20% of patients. One strategy to improve outcomes is the use of induction chemotherapy followed by dCRT. The COSMOS trial demonstrated that induction triplet chemotherapy followed by conversion surgery yielded encouraging results, and this approach is being further evaluated in JCOG1510. Nevertheless, a subset of patients is unfit for cisplatin, for whom FLOT may serve as a promising alternative. The JCOG1804E trial demonstrated favorable outcomes with nivolumab plus FLOT as neoadjuvant therapy in resectable ESCC; however, evidence regarding its use as induction chemotherapy remains lacking. Methods: We retrospectively analyzed cisplatin-unfit patients with unresectable LA-ESCC who received induction FLOT plus nivolumab (IC-FLOT+Nivo) between May 2024 and June 2025. The regimen consisted of docetaxel 50 mg/m², oxaliplatin 85 mg/m², 5-fluorouracil 2600 mg/m², and nivolumab 240 mg/body on day 1, administered every two weeks for four cycles. All patients received prophylactic G-CSF. We evaluated the results of conversion surgery rate, R0 resection, pathological complete response (pCR), and clinical complete response (cCR) after dCRT. Tumor response was evaluated by RECIST v1.1, and adverse events were assessed according to CTCAE v5.0. Results: A total of 21 patients were included to this analysis, with a median follow-up of 7.3 months. Median age was 76 years (range, 52–89), and 67% were male. ECOG performance status was 0 in 48% and 1 in 48%. Clinical T categories were T3 in 57% and T4b in 43%, while clinical stage distribution was stage III in 29%, IVA in 19%, and IVB in 43%. Major reasons for unresectability included invasion of the trachea (52%), aorta (38%), and pulmonary vein (4.8%). Thirteen patients (62%) completed all four cycles of treatment. The objective response rate (ORR) was 64%. Six patients (29%) were considered eligible for curative-intent surgery; among them, four (19%) underwent R0 resection, including one patient (4.8%) who achieved pCR. Of remaining two patients, one (4.8%) received dCRT after R1 resection and achieved cCR, while the other received best supportive care due to poor condition. Regarding toxicity, grade 3–4 neutropenia and leukopenia were observed in 67% and 52%, respectively; rash and anorexia were seen in 4.8% and 9.5%. Febrile neutropenia occurred in 19% of patients. Importantly, no treatment-related fistulas were observed. Conclusions: Induction FLOT plus nivolumab was feasible in cisplatin-unfit unresectable LA-ESCC, achieving meaningful response and surgery without new safety issues. These results support further prospective evaluation.