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Phase 2 Study of mFOLFOX versus mFOLFIRI in Locally Advanced or Metastatic BTC Refractory to First-Line Chemotherapy

Web Exclusives — May 28, 2020

In patients with locally advanced or metastatic biliary tract cancer (BTC), second-line chemotherapy is challenging after progression from first-line gemcitabine/cisplatin, although mFOLFOX has been proven to be superior to active symptom control in the ABC-06 trial.1 Irinotecan is an active drug in other gastrointestinal cancers. This phase 2 study evaluated whether mFOLFIRI was superior to mFOLFOX in second-line treatment of patients with BTC.2

Patients diagnosed with BTC with disease progression after prior gemcitabine/cisplatin were randomized (1:1) to either mFOLFOX or mFOLFIRI. Randomization was stratified by tumor location (intrahepatic vs extrahepatic vs gallbladder vs ampulla of vater) and ECOG performance status (0, 1 vs 2). The primary end point was the overall survival (OS) rate at 6 months.

A total of 120 patients were enrolled in this study and 114 patients were treated (mFOLFOX: 56, mFOLFIRI: 58). The median age was 63 years. Most patients had ECOG 0/1 (89.5%). Tumor location was intrahepatic in 47 patients (41.2%), extrahepatic in 27 (23.7%), gallbladder in 35 (30.7%), and ampulla of vater in 5 (4.4%).

At the median follow-up duration of 25.8 months, the 6-month OS rate was 54.2% and 43.6% in the mFOLFOX and mFOLFIRI groups, respectively. Of 101 evaluable patients (mFOLFOX: 51, mFOFIRI: 50), the objective response rate and disease control rate were 5.9% and 66.7% with mFOLFOX and 4.0% and 64.4% with mFOLFIRI, respectively. Median progression-free survival was 2.8 months with mFOLFOX and 2.1 months with mFOLFIRI (P = .887). Median OS was 6.3 months with mFOLFOX and 5.7 months with mFOLFIRI (P = .472). The most common grade 3/4 adverse events were neutropenia (25.0%) and AST/ALT elevation (16.1%) in the mFOLFOX group and neutropenia (25.9%) and anemia (17.2%) in the mFOLFIRI group. Peripheral neuropathy (37.5%) and thrombocytopenia (37.5%) occurred more frequently in the mFOLFOX group, and vomiting (19.0%) and cholangitis (10.3%) occurred more frequently with mFOLFIRI. No chemotherapy-related deaths were reported.

The authors concluded that the mFOLFIRI regimen was tolerable but not superior to mFOLFOX as second-line therapy for BTC. number NCT03464968.


  1. Lamarca A, et al. J Clin Oncol. 2019;37(15 suppl): Abstract 4003.
  2. Kim JW, et al. ASCO 2020. Abstract 4603.

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