No survival benefit with dacomitinib in pretreated patients with advanced NSCLC

By Lucy Piper, Senior medwireNews Reporter

The irreversible, pan-epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) dacomitinib does not offer a survival benefit in pretreated patients with advanced or metastatic non-small-cell lung cancer (NSCLC), phase III trial results show.

When dacomitinib was compared with placebo in 720 patients who had been previously treated with up to three chemotherapy regimens and the EGFR–TKIs gefitinib or erlotinib, it failed to improve overall survival during a median of 2 years of follow-up.

“Despite advances in the management of non-small-cell lung cancer in the past two decades, additional treatment options are needed for patients with advanced disease after progression with standard therapy”, note Peter Ellis (Juravinski Cancer Centre, Hamilton, Ontario, Canada) and co-investigators.

They considered dacomitinib as a potential option because it has broader activity compared with erlotinib and gefitinib and previous preclinical and clinical evidence has suggested it has activity in NSCLC.

For the current NCIC CTG BR.26 clinical trial, published in The Lancet Oncology, the team randomly assigned 477 patients to receive dacomitinib and 239 to receive placebo.

After a median of 2 years, overall survival was similar between the two groups, at a median of 6.83 months for those receiving dacomitinib and 6.31 months for those receiving placebo.

Dacomitinib was associated with significantly longer progression-free survival (PFS) than placebo, however, at 2.66 versus 1.38 months and a significantly higher objective response rate, at 7% versus 1%. And it also delayed the onset of key lung cancer symptoms, including cough, dyspnoea and pain, compared with placebo.

But in a related comment, Solange Peters (Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland) and Egbert Smit (VU University Medical Center, Amsterdam, the Netherlands) say these “represented benefits of insufficient clinical significance”.

The effect of dacomitinib treatment on survival was unchanged in the presence of an EGFR mutation, but patients with tumours containing KRAS mutations had worse survival with dacomitinib treatment than with placebo.

“These findings lend support to the view that KRAS status could predict patients who should not receive an [EGFR–TKI]”, say Ellis et al.

They conclude that “at present, dacomitinib cannot be recommended as a treatment for patients with [NSCLC]”.

But the team hopes that the ongoing ARCHER 1050 phase III trial comparing first-line dacomitinib and gefitinib in patients with EGFR-mutated cancers “might help determine if dacomitinib has a therapeutic role in the treatment of [NSCLC].”

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