Prospective phase 2 study of neoadjuvant mFOLFOXIRI for potentially recectable cholangiocarcinoma

Cholangiocarcinoma (CCA) has poor outcomes despite curative-intent surgery. Neoadjuvant chemotherapy may improve tumor response and resectability. The phase 2 NEOFOL trial at the Cholangiocarcinoma Research Institute of Khon Kaen University (Khon Kaen, Thailand) evaluated efficacy and safety of neoadjuvant mFOLFOXIRI in patients with potentially resectable CCA. Twenty-five patients received six neoadjuvant cycles of mFOLFOXIRI every 2 weeks, with surgical resection if feasible. The primary endpoint was objective response rate (ORR). Partial response was observed in 11 patients, for an ORR of 44.0%. Stable disease was seen in 10 patients, and progressive disease in four patients. After neoadjuvant therapy, 20 patients (80%) were considered resectable, and 16 (64%) underwent curative-intent resection, with an R0 resection rate of 75%. Major pathologic response occurred in two patients (12.5%). Among resected patients, seven (43.8%) had recurrence, with a median recurrence-free survival of 18.93 months. The median overall survival in the overall cohort was 26.70 months. Radiologic response and surgical resection were significantly associated with longer overall survival. Grade 3-4 neutropenia occurred in 36.0% of patients, and no treatment-related deaths occurred. Health-related quality of life (EQ-5D-5L) remained generally stable during treatment. The authors conclude that neoadjuvant mFOLFOXIRI showed promising antitumor activity, enabling a high rate of curative-intent resection, with manageable toxicity in patients with potentially resectable CCA (graphical abstract).