A phase II study of perioperative FOLFOX4 plus bevacizumab for initially unresectable advanced colorectal cancer (NAVIGATE-CRC-01): Report of interim analysis.

Abstract

e14145 Background: Perioperative chemotherapy combined with surgery for liver metastases is regarded as active strategy in metastatic colorectal cancer (mCRC). However, its impact on initially unresectable or potentially resectable previously untreated advanced CRC (ACRC), regardless of concurrent metastases, remains to be clarified. Methods: A phase II study to evaluate safety and efficacy of perioperative FOLFOX4 plus bevacizumab (BEV) for initially unresectable ACRC was conducted at a single institute in Japan. Previously untreated advanced colon or rectal (Rs-Ra) cancer and initially considered as unresectable ACRC (TNM: Stage IIIb, IIIc or IV) indicating potentially resectable after neoadjuvant chemotherapy (NAC) were eligible for this study. All patients provided their written informed consent. Patients received neoadjuvant FOLFOX4 plus BEV for six cycles. The sixth cycle did not include BEV. Duration between the last administration of BEV and surgery needed at least five weeks. Adjuvant FOLFOX4 plus BEV for six cycles were given after surgery. Completion rate of NAC and possibility of curative surgery were primary end point. Interim analysis of completion rate of NAC was planned at the end of NAC in the twelfth patient. Results: Characteristics of patients were as follows: gender, 8 male and 4 female: location, Sigmoid in 3, Ascending in 1 and Ra in 8: Stage, III in 8 and IV in 4 (liver or lymph node). All patients completed six cycles of NAC. No tumor-related severe adverse events or death were observed. Median duration between last administration of BEV, FOLFOX4 and surgery were 51 days and 34 days, respectively. Objective response to NAC was achieved in nine patients (75%), and no disease progression was observed. Eleven patients underwent curative tumor resection including metastatic lesion. Conclusions: The interim analysis met primary end point and suggests that neoadjuvant FOLFOX4 plus BEV is well tolerated and promise high response rate leading to curative surgery. These data indicate potential survival benefits from perioperative addition of BEV to the FOLFOX4 for initially unresectable ACRC if concurrent metastatic lesion.