313. CLINICAL EVALUATION OF PEMBROLIZUMAB PLUS CISPLATIN AND FLUOROURACIL AS INDUCTION FOR PATIENTS WITH CT4B ESOPHAGEAL SQUAMOUS CELL CARCINOMA
Authors: Hokamura Nobukazu , Fukagawa Takeo , Fukushima Ryoji , Kiyokawa Takashi , Horikawa Masahiro , Soeda Naruyoshi , Suzuki Yusuke , Midorikawa Hironori 
Published: September 2024

Abstract

Background
Definitive chemoradiotherapy (dCRT) is a standard treatment for patients with cT4b esophageal squamous cell cancer (ESCC). In these 3 decades, radiation technique has been improved, and chemotherapy with cisplatin, fluorouracil, and/or taxans was combined before and after dCRT. However, its CR rate remains around 25% and its 3-year survival rate also remains below 30%. Although conversion surgery has been applied to improve the survival of these patients, no study has shown significant superiority to CR after dCRT in survival to date. Chemotherapy of pembrolizumab plus cisplatin and fluorouracil was applied to patients with unresectable or recurred esophageal cancer and demonstrated significant survival benefit and good objective response. We provided this therapy as induction to improve the therapeutic result of patients with cT4b ESCC.

Method
From April 2022 to August 2023, 11 untreated patients with cT4b ESCC had this chemotherapy as induction, with pembrolizumab 200 mg plus chemotherapy (5-fluorouracil 800 mg/m2 on days 1-5 plus cisplatin 80 mg/m2 on day 1) once every 3 weeks. Patients with cervical lymph node metastasis were included. After 2 or 3 cycles, the therapeutic effect was evaluated according to RECIST. Adverse events were evaluated according to CTCAE.

Result
Average age was 70, and 3 patients had cervical lymph node metastasis. Objective response rate was 82% (CR 1, PR 8). In these 9 patients, the volume of tumors shrank by more than 60% within 11 weeks. Over Grade 3 neutropenia developed in 2 (18%), but no G-CSF was administered. Gastric ulcer perforation developed in 1 (9%). In 2 patients, the dose of cisplatin should be modified due to renal damage. One patient had prolonged renal damage and had conversion surgery after 1 cycle. Eight patients had dCRT. One of 8 terminated dCRT due to another disease. Two of 8 just finished dCRT, and one is under dCRT. Of 3 were evaluated as CR, and followed without any treatment. Local and lymphatic recurrence developed in one PR patient. To date, no specific adverse events relating to pembrolizumab developed during and after dCRT. Of the 2 had conversion surgery without any severe post-operative complications.

Discussion and Conclusion
In our preliminary study, chemotherapy of pembrolizumab plus cisplatin and fluorouracil showed good objective response (82%) and early tumor shrinkage (more than 60% within 11 weeks). Over grade 3 hematological adverse events developed in only 18% of patients. These results suggest this regimen could be administered to patients with cT4b ESCC as induction especially followed by dCRT. This regimen can reduce tumor volume and control lymphatic spread, and these factors seem to improve prognosis and prevent fatal complications such as fistula or stricture of patients with cT4b ESCC who have dCRT. We plan a clinical trial of this chemotherapy followed by dCRT for patients with cT4b ESCC.