The safety and short-term efficacy of induction DCF plus nivolumab therapy in patients with unresectable locally advanced esophageal squamous cell carcinoma.
Authors: Momoko Sano, Shun Yamamoto, Kazuhiro Shiraishi, Hiroshi Imazeki, Yuri Yoshinami, Nozomu Ogura, Mai Itoyama, Kazuki Yokoyama, Yoshitaka Honma, Daisuke Kurita, Koshiro Ishiyama, Junya Oguma, Tairo Kashihara, Taiki Hashimoto, Hiroyuki Daiko, Yasuyuki Seto, Ken Kato
Journal: Journal of Clinical Oncology (2025)

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.