First-line dacomitinib may improve advanced NSCLC survival

Dec 11 2014

By medwireNews Reporters

Preliminary research suggests that the second-generation tyrosine kinase inhibitor (TKI) dacomitinib may improve progression-free survival (PFS) in patients with advanced non-small-cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutations.

Noting that the majority of patients develop resistance to the first-generation TKIs, such as gefitinib and erlotinib, Pasi Jänne (Dana Farber Cancer Institute, Boston, Massachusetts, USA) and co-workers explain that alternative agents are needed to improve patient outcomes.

The open-label, phase II trial included 89 treatment-naïve patients with stage IIIB or IV NSCLC who were selected for dacomitinib once-daily treatment on the basis of clinical markers (never or former light smokers) or molecular markers (absence of KRAS mutation in non-Asian patients or EGFR mutation).

As reported in The Lancet Oncology, after 4 months of treatment PFS was 76.8%, with median PFS estimated to be 11.5 months, and median overall survival 29.5 months.

Forty-five patients had EGFR-activating mutations, in exon 19 (n=25) or exon 21 (n=20), and in these patients, median PFS and median overall survival were 18.2 months and 40.2 months, respectively. There was no noticeable difference between participants with exon 19 and those with exon 21 mutations with respect to these outcome measures.

However, median PFS was shorter in participants carrying wild-type EGFR than in those with EGFR-activating mutations at 2.1 versus 18.2 months.

The toxicity profile of dacomitinib was “typical of other EGFR inhibitors”, the researchers note, with diarrhoea, dermatitis acneiform, dry skin and stomatitis the most common side effects. However, 30% of participants needed a dose reduction in the initial two cycles of treatment, prompting the researchers to reduce the starting dose from 45 mg to 30 mg per day.

“The findings from this single-group, phase 2 trial show promising [PFS] for patients with EGFR-mutant [NSCLC] treated with dacomitinib”, Jänne et al conclude.

They add: “These findings have led to a phase 3 clinical trial comparing dacomitinib with gefitinib in EGFR-mutant [NSCLC] to identify the most effective first-line EGFR inhibitor.”

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