By Liam Davenport
In patients with non-small-cell lunch cancer (NSCLC), dacomitinib confers a significant progression-free survival (PFS) benefit over erlotinib across a range of clinical and molecular subgroups, the results of an international study indicate.
The reversible tyrosine kinase inhibitors erlotinib and gefitinib target single members of the human epidermal growth factor receptor (HER/EGFR) family, and have shown effectiveness in the first-line treatment of NSCLC with EGFR-sensitizing mutations.
Noting that dacomitinib is an irreversible pan-HER inhibitor, Suresh Ramalingam, from Emory University, in Atlanta, Georgia, USA, and colleagues randomly assigned 189 patients with NSCLC to receive either dacomitinib 45 mg or erlotinib 150 mg once daily.
All NSCLC patients had an Eastern Cooperative Oncology Group performance status of 0 to 2, no prior HER-directed therapy, and had received up to two prior chemotherapy regimens.
The results, published in the Journal of Clinical Oncology, indicate that median PFS was significantly greater with dacomitinib than erlotinib, at 2.86 versus 1.91 months (hazard ratio [HR]=0.66). The mean duration of response was 16.56 months for dacomitinib and 9.23 months for erlotinib.
Dividing the patients by tumor type, the team found that median PFS was 3.71 months with dacomitinib and 1.91 with erlotinib in patients with KRAS wild-type tumors (HR=0.55), and 2.21 months and 1.68 months, respectively, in patients with KRAS wild-type/EGFR wild-type tumors (HR= 0.61).
There was no significant difference in median overall survival between the two treatment groups, at 9.53 months in patients treated with dacomitinib and 7.44 months in those given erlotinib.
Treatment-related adverse events were more frequent in dacomitinib-treated patients than in those given erlotinib, most commonly grade 1 and 2 skin and gastrointestinal events. Treatment-related dose reductions were required in 40.9% and 17.0% of patients, respectively.
"The results documented here for dacomitinib suggest that irreversible pan-HER inhibition may offer a new treatment option for patients with advanced NSCLC, potentially representing an effective alternative to reversible inhibition of EGFR," the researchers conclude.
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