Novel TKI Therapy Plus Gemcitabine Does Not Improve OS in Pancreatic Cancer

A new tyrosine kinase inhibitor (TKI) in combination with gemcitabine does not improve overall survival (OS) any more than gemcitabine alone for patients with advanced pancreatic cancer, according to a study published in The Lancet Oncology (published online March 2017; doi:10.1016/S1470-2045(17)30084-0).
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Epidermal growth factor receptor (EGFR) TKIs have demonstrated marginal effects in improving survival outcomes when used in combination with gemcitabine-based chemotherapy in patients with locally advanced and metastatic pancreatic cancer. Vandetanib – a novel TKI – inhibits VEGFR2, RET, and EGFR, all of which are involved in the pathogenesis of pancreatic cancer. The effects of vandetanib in combination with gemcitabine for treating advanced pancreatic cancer have yet to be studied.

Gary Middleton, MD, University of Birmingham (UK), and colleagues conducted a phase 2, double-blind, multicenter, randomized, placebo-controlled trial to investigate the efficacy of vandetanib when used in combination with gemcitabine in patients with advanced pancreatic cancer. A total of 142 previously untreated adult patients (aged ≥ 18 years) were randomly assigned 1:1 to receive oral vandetanib (300 mg/day) plus intravenous infusion gemcitabine (1000 mg/m2 once weekly) or matching placebo plus gemcitabine until disease progression or unacceptable toxicity. The primary outcome was OS in the intention-to-treat population.

Results of the study showed no significant difference in OS between the vandetanib and placebo groups (hazard ratio, 1.21; 80.8% CI, 0.95-1.53; P = .303). The median OS was 8.83 months (95% CI, 7.11-11.58) in the vandetanib group and 8.95 months (95% CI, 6.55-11.74) in the placebo group.

Common grade 3-4 adverse events as a result of vandetanib treatment were neutropenia (49%), thrombocytopenia (28%), fatigue (24%), leukopenia (17%), and hypertension (13%). There were no treatment-related deaths in either group.

Researchers concluded that the addition of vandetanib to gemcitabine monotherapy did not have any clinically significant impact on OS in patients with locally advanced or metastatic pancreatic cancer. However, researchers are not discouraged from further studying TKI therapy in such populations.

“TKIs might still have potential in the treatment of pancreatic cancer but further development requires the identification of biomarkers to specifically identify responsive cancer subtypes,” they wrote. – Zachary Bessette