A Phase II Trial of Pemetrexed Plus Oxaliplatin in Patients With Advanced Biliary Tract Cancer After Failure of Gemcitabine Plus Cisplatin-based Chemotherapy.

Background/aim: This study aimed to evaluate the efficacy and safety of pemetrexed/oxaliplatin (PemOx) in patients with advanced or metastatic biliary tract cancer (aBTC) after failure of gemcitabine/cisplatin (GP)-based chemotherapy.

Patients and methods: This investigator-initiated, multicenter trial was conducted at four tertiary referral centers in South Korea. PemOx was administered as follows: intravenous Pem 500 mg/m² and Ox 120 mg/m² on day 1, every three weeks. The primary endpoint was the objective response rate (ORR). Secondary endpoints included progression-free survival (PFS), overall survival (OS), and treatment-related adverse events (TRAEs). Based on the Minimax two-stage design, a total of 30 patients were planned to be enrolled to detect an increase in the ORR from 5% to 20%, with two-sided α=0.05, β=0.2, and a 10% dropout rate.

Results: Between November 2023 and November 2024, 30 patients were enrolled. The median age of the patients was 68 years, and 70% were male. Five patients achieved a partial response, resulting in an ORR of 16.7% and a disease control rate of 76.7%. With a median follow-up duration of 11.0 months (range=6.9-15.1 months), the median PFS and OS were 3.6 months [95% confidence interval (CI)=1.9-5.3] and 9.9 months (95%CI=6.8-13.0), respectively. Dose delays or reductions were required in 13 (43.3%) and four (13.3 %) patients, respectively. Grade 3 TRAEs were reported in three patients (10%). No grade ≥4 TRAEs were reported.

Conclusion: PemOx showed modest efficacy and manageable TRAEs in patients with aBTC after the failure of first line GP-based chemotherapy, although the primary endpoint was not met.