Gemcitabine and Erlotinib with or without Oxaliplatin in Previously Untreated Advanced Pancreatic Cancer: A Randomized Phase II Trial

PURPOSE: Erlotinib has been the only targeted agent to show significantly improved outcomes in pancreatic adenocarcinoma when combined with gemcitabine. We aimed to evaluate whether the addition of oxaliplatin to a combination gemcitabine/erlotinib treatment conferred a clinical benefit in patients with locally advanced unresectable or metastatic pancreatic cancer. MATERIALS AND METHODS: Chemotherapy-naïve patients with locally advanced or metastatic pancreatic cancer were randomly assigned to receive GEMOX-T [gemcitabine 1000 mg/m(2) and oxaliplatin 50 mg/m(2) on day 1 (D1) and D8 plus erlotinib 100 mg daily for 3 weeks] or GT (gemcitabine 1000 mg/m(2) on D1 and D8 plus erlotinib 100 mg daily for 3 weeks). The primary endpoint was the overall response rate (ORR). RESULTS: Between 2013 and 2016, 65 patients were assigned to a treatment group (33 in the GEMOX-T arm, 32 in the GT arm). The ORR was 18.2% [95% confidence interval (CI), 8.82–27.58] in the GEMOX-T arm and 6.2% (95% CI, 0.34–12.06) in the GT arm (p=0.051). The disease control rate was significantly superior in the GEMOX-T arm compared to the GT arm (72.7% vs. 43.8%, p=0.019). After a median follow-up of 19.7 months, the median progression-free survival (PFS) was 3.9 months for the GEMOX-T arm and 1.4 months for the GT arm (p=0.033). However, this did not translate to an improvement in overall survival. The most common grade 3 or higher hematologic adverse events were neutropenia (16.9%) and anemia (13.8%). CONCLUSION: The addition of oxaliplatin to a first-line gemcitabine/erlotinib regimen demonstrated higher response rates and significantly improved PFS in patients with locally advanced or metastatic pancreatic cancer.