Adding Vandetanib to Gemcitabine in Locally Advanced or Metastatic Pancreatic Carcinoma


Key Points

  • In patients with previously untreated locally advanced or metastatic pancreatic carcinoma, adding vandetanib to gemcitabine did not improve overall survival.
  • No survival benefit was evident in either locally advanced or metastatic disease.

In a UK phase II trial reported in The Lancet Oncology, Middleton et al found that adding the multi–tyrosine kinase inhibitor vandetanib (Caprelsa) to gemcitabine did not improve overall survival in patients with previously untreated locally advanced or metastatic pancreatic carcinoma.

Study Details

In the double-blind trial, 142 patients from 18 UK sites were randomized between October 2011 and October 2013 to receive gemcitabine at 1,000 mg/m² via 30-minute infusion weekly for 7 weeks followed by a 1-week break and then 3-week cycles with a 1-week break until disease progression plus either oral vandetanib at 300 mg/d once daily (n = 72) or placebo (n = 70). The primary endpoint was overall survival.

Overall Survival

At database lock in July 2015, at median follow-up of 24.9 months, death had occurred in 70 of 72 patients (97%) in the vandetanib group and 61 of 70 patients (87%) in the placebo group. Median overall survival was 8.83 months vs 8.95 months (hazard ratio [HR] = 1.21, P = .303). Median overall survival was 12.1 months vs 10.9 months (HR = 1.13, P = .71) among 41 patients with locally advanced disease and 7.11 months vs 7.20 months (HR = 1.20, P = .38) among 101 patients with metastatic disease.

Adverse Events

The most common grade 3 or 4 adverse events in the vandetanib group were neutropenia (49% vs 31% in placebo group), thrombocytopenia (28% vs 23%), fatigue (24% vs 21%), leukopenia (17% vs 19%), hyponatremia (14% vs 11%), and hypertension (13% vs 16%). No treatment-related deaths were observed during the study.

The investigators concluded: “The addition of vandetanib to gemcitabine monotherapy did not improve overall survival in advanced pancreatic cancer. Tyrosine kinase inhibitors might still have potential in the treatment of pancreatic cancer, but further development requires the identification of biomarkers to specifically identify responsive cancer subtypes.”

The study was funded by Cancer Research UK and AstraZeneca.

John P. Neoptolemos, MD, of Cancer Research UK Liverpool Cancer Trials Unit, University of Liverpool, is the corresponding author of The Lancet Oncology article.

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