A randomized controlled phase III study comparing surgery alone versus adjuvant nivolumab versus adjuvant S-1 for locally advanced esophageal cancer with no pathological complete response: JCOG2206 (SUNRISE Trial).
Authors: Matsuda Satoru , Kita Ryosuke , Nomura Motoo , Kitagawa Yuko , Kato Ken , Goto Rei , Yoshioka Takashi , Yamamoto Shun , Tsushima Takahiro , Machida Ryunosuke , Sasaki Keita , Fukuda Haruhiko , TAKEUCHI HIROYA 
Published: January 2024

TPS417 Background: On the basis of JCOG1109, neoadjuvant chemotherapy (NAC) with Docetaxel, Cisplatin, and 5-FU (DCF) has become one of the standard treatments for locally advanced esophageal squamous cell carcinoma (LAESCC). Although the efficacy of adjuvant therapy with nivolumab after preoperative chemoradiotherapy for LAESCC has been proven by CheckMate 577, the survival benefits of adjuvant therapy after NAC remain controversial. Additionally, a single-arm phase II trial of adjuvant S-1 for LAESCC who received NAC demonstrated favorable survival outcomes and safety. Methods: Eligibility criteria include the followings: thoracic esophageal squamous cell carcinoma, adenosquamous carcinoma, or basaloid squamous cell carcinoma, reception of NAC (at most three courses of DCF or two courses of Cisplatin plus 5-FU) and a diagnosis of clinical stage I (except for T1N0), II, III, IVA (except for T4), or IVB (only supraclavicular lymph node metastasis except for T4), right thoracoabdominal esophagectomy with D2 or higher lymph node dissection, R0 resection was performed, residual pathological disease in the resected specimens [ypStage T0-4aN1-3M0, T1-4aN0M0, T0-4aNanyM1 (only supraclavicular lymph node metastasis)], aged 18-80 years, ECOG performance status 0 or 1, and adequate organ function. The primary endpoint is relapse-free survival (RFS), and the secondary endpoints are disease-free survival, overall survival, adverse events, and incremental cost-effectiveness ratio. After the confirmation of patient eligibility including pathological diagnosis, patients will be randomized (1:1:1) to either the observation alone arm, adjuvant nivolumab arm (240 mg/body every two weeks or 480 mg/bodies every four weeks for one year), or adjuvant S-1 arm (four courses of twice-daily oral S-1 for four weeks followed by two weeks of rest for 6 month, three dose levels of S-1 are set according to the patient’s body surface area (BSA), as follows: BSA < 1.25 m2, 40 mg; BSA 1.25–1.50 m2, 50 mg; BSA > 1.50 m2, 60 mg, twice a day). We assumed a three-year RFS of 60% in the observation alone arm and expected an 11% increase for the nivolumab arm and the S-1 arm (HR = 0.67). The total required sample size was calculated as 435 (145 per arm) to achieve the desired power of 70% for each pair comparison (observation alone arm vs. the nivolumab arm and observation alone arm vs. S-1 arm) with an overall one-sided alpha of 5%, an accrual period of 5.5 years, and a follow-up period of three years. The planned sample size was set at 450 patients (150 patients per arm). This trial has been registered in the Japan Registry of Clinical Trials as jRCTs031230219. This trial was initiated in July 2023, and the first patient was enrolled in September 2023. Clinical trial information: jRCTs031230219 .