(ChemotherapyAdvisor) – Dacomitinib, an irreversible inhibitor of human epidermal growth factor receptors (EGFR)/HER1, HER2, and HER4, demonstrated significantly improved progression-free survival (PFS) when compared with erlotinib in patients with advanced non-small cell lung cancer (NSCLC), results of a randomized phase 2 study published in the Journal of Clinical Oncology online July 2 have found.

The global open-label trial, the first to compare an irreversible pan-HER tyrosine kinase inhibitor (TKI) with a reversible EGFR-selective TKI, randomly assigned 188 patients with NSCLC and no prior HER-directed therapy and one or two prior chemotherapy regimens to dacomitinib 45mg/day or erlotinib 150mg/day.

Median PFS, the primary end point, was 2.86 months in the dacomitinib arm and 1.91 months in the erlotinib arm (HR 0.66 [95% CI, 0.47–0.91; two-sided P=0.012). Patients with KRAS wild-type tumors had a median PFS of 3.71 when treated with dacomitinib vs 1.91 months for erlotinib (HR 0.55 [95% CI, 0.35–0.85]; two-sided P=0.006); for those with KRAS wild-type/EGFR wild-type tumors, median PFS was 2.21 months vs 1.84 months, respectively (HR 0.61 [95% CI, 0.37–0.99]; two-sided P=0.043).

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Median overall survival was 9.53 months in the dacomitinib arm and 7.44 months in the erlotinib arm (HR 0.80 [95% CI, 0.56–1.13]; two-sided P=0.205).

Consistent with the expected toxicities of EGFR TKIs, skin effects and diarrhea were the prominent adverse events, they reported, which were predominantly grade 1 to 2, and more frequent with dacomitinib.

The investigators noted that PFS benefit with dacomitinib “was observed in most clinical and molecular subsets, notably KRAS wild-type/EGFR any status, KRAS wild-type/EGFR wild-type, and EGFR mutants.”

An ongoing phase 3 study (ARCHER 1009 [Advanced Research for Cancer Targeted Pan-HER Therapy]) will confirm the results of this study for the treatment of second- and third-line therapy in patients with advanced NSCLC. “This study includes coprimary end points (PFS in all patients and in patients with wild type KRAS/EGFR any status) to allow evaluation of dacomitinib in an unselected population and to prospectively evaluate the relationship between KRAS molecular status and clinical outcome,” they wrote.