Patients with advanced pancreatic cancer given axitinib in addition to the standard treatment of gemcitabine show a trend towards increased survival compared with those given gemcitabine alone. The findings now require further investigation in a phase III trial. These are the conclusions of authors of an Article published early Online and in an upcoming edition of The Lancet.
Pancreatic cancer is responsible for 227 000 deaths worldwide every year, and is the eighth most common cause of cancer-related death. In North America, pancreatic cancer is the fourth leading cause of cancer death, with about 37 700 new cases and 33 300 deaths estimated in 2008. The 5-year survival rate the disease is one of the lowest, at 5%. Gemcitabine has been the standard of care for more than a decade, however combination with other cytotoxic or biological agents has been disappointing, and thus new therapies in conjunction with gemcitabine are needed. Axitinib is a potent and selective orally-taken inhibitor of vascular endothelial growth factor receptors 1, 2 and 3, which have an important role in pancreatic cancer. Dr Jean-Philippe Spano and Professor Olivier Rixe, Groupe Hospitalier Pitié-Salpêtrière, Université Paris 6, Paris, France, and colleagues did a randomised phase II study to assess the efficacy of gemcitabine plus axitinib versus gemcitabine alone.
The study analysed 103 patients with inoperable, locally advanced or metastatic pancreatic cancer, who were randomised in an approximate two-to-one ratio to receive either gemcitabine (1000 mg/m2) plus axitinib at a starting dose of 5mg twice daily (69 patients), or gemcitabine alone (1000 mg/ m2) (34 patients). The researchers found that median overall survival was longer with the axitinib group (6.9 months) compared with the gemcitabine only group (5.6 months), although the finding was not statistically significant and thus can only be described as a trend. There was a 29% decrease in risk of death (hazard ratio of 0.71) favouring the gemcitabine plus axitinib group.
The authors conclude: “Gemcitabine plus axitinib showed a similar safety profile to gemcitabine alone; the small non-statistically significant gain in overall survival needs to be assessed in a randomised phase III trial.”
They add that such a global phase III trial is currently enrolling patients, and will be studying the efficacy of axitinib at 10mg, although all patients will have a starting dose of 5mg.
In an accompanying Comment, Professor Philip A Philip, Karmanos Cancer Center, Detroit, MI, USA says: “We need an improved understanding of the complex interactions between pancreatic cancer cells and their specific microenvironment to better plan the next generation of clinical trials that encompass the cancer process rather than a single target… Close collaboration between clinical and basic scientists in partnership with the drug industry is key for future success.”
Professor Jean-Philippe Spano and Professor Olivier Rixe, Groupe Hospitalier Pitié-Salpêtrière, Université Paris 6, Paris, France T) +33 1 42160472 (Prof Spano) +1 301-435-2279 (Prof Rixe-now working in USA) E) rixeo@mail.nih.gov / jean-philippe.spano@psl.ap-hop-paris-fr
Professor Philip A Philip, Karmanos Cancer Center, Detroit, MI, USA T) +1 313 576 8746 E) philipp@karmanos.org
http://multimedia.thelancet.com/pdf/press/Pancreaticcancer.pdf
Journal
The Lancet