Dacomitinib ‘not superior’ to erlotinib in advanced NSCLC

By Shreeya Nanda, Senior medwireNews Reporter

Dacomitinib, an irreversible, pan-epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), does not improve outcomes compared with the first-generation EGFR–TKI erlotinib in patients with advanced non-small-cell lung cancer (NSCLC), irrespective of their KRAS mutation status, finds the ARCHER 1009 study.

In a previous phase II study in patients with NSCLC, dacomitinib showed “favourable efficacy” compared with erlotinib, therefore Suresh Ramalingam (Emory University School of Medicine, Atlanta, Georgia, USA) and co-workers compared the two EGFR–TKIs in a phase III trial.

A total of 878 patients with locally advanced or metastatic NSCLC who had previously been treated with one or two systemic chemotherapy regimens were randomly assigned in a 1:1 ratio to receive dacomitinib or erlotinib and followed up for a median of 7.1 months.

Median progression-free survival was identical in both treatment groups, at 2.6 months. When just the patients with wild-type KRAS were considered, the median progression-free survival remained 2.6 months for both the dacomitinib and erlotinib groups.

Receipt of dacomitinib did not have a significant effect on median overall survival compared with erlotinib treatment, at 7.9 and 8.4 months, respectively. And when patients were stratified by KRAS status, the median overall survival among those with wild-type KRAS remained similar in the dacomitinib and erlotinib groups, at 8.1 versus 8.5 months.

Grade 3 or 4 adverse events occurred more frequently in patients who received dacomitinib compared with those given erlotinib, with diarrhoea (11 vs 2%), rash (7 vs 3%) and stomatitis (3 vs <1%) being the most common toxicities.

Although the data are not yet mature, dacomitinib and erlotinib have similar efficacy in the subset of patients with EGFR mutations, report the researchers in The Lancet Oncology.

In an accompanying comment, Solange Peters (Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland) and Egbert Smit (VU University Medical Center, Amsterdam, the Netherlands) point out that this argues “against a preventive role of pan-HER inhibition in the development of acquired resistance against EFGR tyrosine kinase inhibitors.”

The commentators recommend that “use of EGFR tyrosine kinase inhibitors in EGFR wild-type advanced [NSCLC] should be restricted to erlotinib in its indication defined 10 years ago in the BR.21 trial, where only a small improvement over best supportive care in clinical outcome should be expected.”

Ramalingam et al. explain that they “evaluated the efficacy of dacomitinib and erlotinib in KRAS wild-type patients, with the premise that this approach would enrich the study population with patients with both known EGFR mutational status and unknown factors associated with preferential dacomitinib efficacy.”

However, they conclude: “In view of our findings, and because patients with KRAS wild-type non-small-cell lung cancer are a heterogeneous population, the future use of this strategy should be questioned, and treatment with dacomitinib should be limited solely to patients with EGFR mutant [NSCLC] if findings from the ARCHER 1050 study show benefit for patients with EGFR-activating mutations.”

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