The safety and short-term efficacy of induction DCF plus nivolumab therapy in patients with unresectable locally advanced esophageal squamous cell carcinoma.

425 Background: Definitive chemoradiotherapy (dCRT) is the standard treatment for unresectable locally advanced esophageal squamous cell carcinoma (LA-ESCC) based on the results of the JCOG 0303 study. However, the prognosis in this population remains poor with a median overall survival (OS) of 13.1 months, and fistula formation was reported in about 20% of patients who received dCRT. In such a circumstance, a more effective and safer treatment strategy, such as induction chemotherapy followed by conversion surgery or dCRT, was developed. A phase II study of induction chemotherapy consisting of docetaxel (DTX), cisplatin (CDDP), and 5-fluorouracil (5-FU) (DCF) therapy (IC-DCF) showed a conversion rate of 37.5%, promising efficacy with a median OS of 33.8 months and a fistula formation rate of 4.2%. Therefore, we evaluated whether adding nivolumab to IC-DCF (IC-DCF+Nivo) could improve clinical outcomes. Methods: We retrospectively reviewed the medical records of patients with unresectable LA-ESCC who received IC-DCF+Nivo between Nov 2023 and Aug 2024. IC-DCF+Nivo (DTX 70mg/m2 day1, CDDP 70mg/m2 day1, 5-FU 750mg/m2 day1-5, Nivo 360 mg/body day1, every 3 weeks) was administered for 3 courses. We administered prophylactic levofloxacin from day 5 to day 15 during each cycle, and used granulocyte colony-stimulating factor (G-CSF) as a treatment. We evaluated adverse events according to the CTCAE ver5.0 during induction chemotherapy as safety, and objective response rate (ORR) of IC-DCF+Nivo according to the RECIST version 1.1., conversion surgery rate, complete resection (R0) rate, pathological complete response (pCR) rate and clinical CR (cCR) rate after dCRT as efficacy. Results: The median follow-up period was 5.5 months. We identified 23 eligible LA-ESCC patients, median age (range): 65 (44-76), 83% male, PS 0/1: 57%/44%, T status T3/T4b 44%/57%, clinical stage III/IVA/IVB 22%/57%/22%. Seven patients (30%) had supraclavicular lymph node metastases, and the most common unresectable factors were tracheal invasion (52%), bronchial invasion (22%) and aortic invasion (13%) of primary tumor or metastatic lymph nodes. Eighteen patients (78%) completed the 3 courses of IC-DCF+Nivo. The frequent grade 3-4 hematological adverse events were neutropenia (13/23, 57%) and anemia (3/23, 13%), and 1 patient (4.3%) had grade 3 diarrhea as non-hematological toxicity. Febrile neutropenia occurred in 3 patients (13%), and G-CSF was used in 7 patients (30%). One patient (4.3%) experienced primary tumor perforation. The ORR after 3 cycles of induction chemotherapy was 53%. Fourteen patients (61%) achieved resectability, and 10 patients (44%) underwent surgery. R0 resection rate was 90% (9/10), and the pCR rate was 20% (1/10). No one achieved cCR in dCRT. Conclusions: Induction DCF plus nivolumab therapy showed well-tolerated and well conversion rate.