Protocol for a phase II study to evaluate the efficacy and safety of nivolumab as a postoperative adjuvant therapy for patients with esophageal cancer treated with preoperative docetaxel, cisplatin plus 5-fluorouracil treatment (PENTAGON trial).

BACKGROUND: In Japan, preoperative adjuvant chemotherapy followed by surgical resection is the standard treatment for patients with locally advanced esophageal squamous cell carcinoma. However, the risk of recurrence after surgical resection remains high. Although a randomized controlled trial evaluating the efficacy of nivolumab, a fully human monoclonal anti-programmed death 1 antibody, as postoperative adjuvant therapy after neoadjuvant chemoradiotherapy and surgery established its superior efficacy as adjuvant therapy, the efficacy for patients who received preoperative adjuvant chemotherapy has not been demonstrated. This study aims to elucidate the efficacy and safety of nivolumab as postoperative adjuvant therapy for patients with esophageal squamous cell carcinoma after preoperative adjuvant chemotherapy with docetaxel and cisplatin plus 5-fluorouracil followed by surgical resection. METHODS: This study is a multi-institutional, single-arm, Phase II trial. We plan to recruit 130 esophageal squamous cell carcinoma patients, who have undergone preoperative adjuvant chemotherapy with docetaxel and cisplatin plus 5-fluorouracil followed by surgical resection. If the patient did not have a pathological complete response, nivolumab is started as a postoperative adjuvant therapy within 4-16 weeks after surgery. The nivolumab dose is 480 mg/day every four weeks. Nivolumab is administered for up to 12 months. The primary endpoint is disease-free survival; the secondary endpoints are overall survival, distant metastasis-free survival, and incidence of adverse events. DISCUSSION: To our knowledge this study is the first trial establishing the efficacy of nivolumab as postoperative adjuvant therapy for patients with esophageal squamous cell carcinoma after preoperative adjuvant chemotherapy with docetaxel and cisplatin plus 5-fluorouracil followed by surgical resection. In Japan, preoperative adjuvant chemotherapy followed by surgery is a well-established standard treatment for resectable, locally advanced esophageal squamous cell carcinoma. Therefore, developing an effective postoperative adjuvant therapy has been essential for improving oncological outcomes.

Prognostic significance of pathological response to preoperative chemoradiotherapy in patients with locally advanced rectal cancer.

BACKGROUND: Preoperative chemoradiotherapy (CRT) is widely used in the treatment of locally advanced rectal cancer (LARC). Pathological response to CRT has been shown to be a potential prognostic predictor in rectal cancer patients. The aim of this study was to determine the prognostic significance of pathological response to preoperative CRT in LARC patients. METHODS: Thirty-two patients with LARC were retrospectively analyzed to determine the relationships of pathological response and clinicopathological characteristics to survival outcomes. Patients received CRT with tegafur/uracil and leucovorin. Radiotherapy was administered in fractions of 1.8 Gy/day and 5 days per week. The total dose of radiation delivered was 45 Gy. RESULTS: All patients underwent total mesorectal excision with lymph node dissections after CRT, and resected specimens were examined pathologically. Four patients showed pathological complete response, 14 showed good response, and 14 showed poor response. Pathological complete or good response was associated with longer survival (P = 0.041). Clinicopathological factors excluding gender were not correlated with outcome. No factor was associated with recurrence. CONCLUSION: Pathological response to preoperative CRT may be a useful prognostic predictor in patients with LARC.