Vandetanib has some advantage over gefitinib in non-small-cell lung cancer

NEW YORK (Reuters Health) - Vandetanib demonstrated a significant prolongation of progression-free survival compared with gefitinib in patients with locally advanced or metastatic non-small-cell lung cancer (NSCLC) in a recent study by U.S. and European researchers. However, overall survival was not improved.

Gefitinib is an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor. Vandetanib also targets EGFR-dependent tumor cell proliferation and survival, but in addition targets vascular endothelial growth factor receptor (VEGFR)-dependent tumor angiogenesis.

The current study, published online March 30 by the Journal of Clinical Oncology, recruited 168 patients at 37 centers in 6 countries. All patients had stage IIIB or IV NSCLC and had experienced failure of first-line chemotherapy, with or without second-line therapy.

In part A of the trial, participants were randomly assigned to receive once-daily vandetanib 300 mg or gefitinib 250 mg until disease progression or evidence of toxicity occurred or the participant withdrew consent. After a 4-week washout period, eligible patients (those who experienced disease progression or withdrew because of an adverse event) had the option to switch to the other agent for part B.

Dr. Ronald Natale at the Cedars-Sinai Outpatient Cancer Center in Los Angeles, California, and colleagues report that median progression-free survival was significantly higher in part A among patients assigned to vandetanib (11.0 weeks) than among those assigned to gefitinib (8.1 weeks). In part B, median progression-free survival was 65 days in patients receiving vandetanib after gefitinib, versus 28 days in patients receiving gefitinib after vandetanib.

Among all patients in the study, however, overall survival was not significantly higher in patients initially randomized to receive vandetanib.

There were 127 deaths (76%) at the time of data cutoff in July 2005: 61 patients initially assigned to vandetanib and 66 initially assigned to gefitinib. The primary cause of death was disease progression, that is, NSCLC or a related condition.

The researchers comment, "It is not clear why benefits in progression-free survival with vandetanib in part A did not translate into an overall survival advantage."

They also noted that "the relative contribution of anti-VEGFR and anti-EGFR activity to the antitumor efficacy of vandetanib remains to be established."

In part A, the vandetanib group experienced a higher incidence of discontinuation because of adverse events (27%) than did the gefitinib group (11%). On the other hand, most adverse events from either agent were mild (grade 1 or 2).

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