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Randomized Phase II Study of Dacomitinib (PF-00299804), an Irreversible Pan-Human Epidermal Growth Factor Receptor Inhibitor, Versus Erlotinib in Patients With Advanced Non-Small-Cell Lung Cancer.

PURPOSE This randomized, open-label trial compared dacomitinib (PF-00299804), an irreversible inhibitor of human epidermal growth factor receptors (EGFR)/HER1, HER2, and HER4, with erlotinib, a reversible EGFR inhibitor, in patients with advanced non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS Patients with NSCLC, Eastern Cooperative Oncology Group performance status 0 to 2, no prior HER-directed therapy, and one/two prior chemotherapy regimens received dacomitinib 45 mg or erlotinib 150 mg once daily. Results One hundred eighty-eight patients were randomly assigned. Treatment arms were balanced for most clinical and molecular characteristics. Median progression-free survival (PFS; primary end point) was 2.86 months for patients treated with dacomitinib and 1.91 months for patients treated with erlotinib (hazard ratio [HR] = 0.66; 95% CI, 0.47 to 0.91; two-sided P = .012); in patients with KRAS wild-type tumors, median PFS was 3.71 months for patients treated with dacomitinib and 1.91 months for patients treated with erlotinib (HR = 0.55; 95% CI, 0.35 to 0.85; two-sided P = .006); and in patients with KRAS wild-type/EGFR wild-type tumors, median PFS was 2.21 months for patients treated with dacomitinib and 1.84 months for patients treated with erlotinib (HR = 0.61; 95% CI, 0.37 to 0.99; two-sided P = .043). Median overall survival was 9.53 months for patients treated with dacomitinib and 7.44 months for patients treated with erlotinib (HR = 0.80; 95% CI, 0.56 to 1.13; two-sided P = .205). Adverse event-related discontinuations were uncommon in both arms. Common treatment-related adverse events were dermatologic and gastrointestinal, predominantly grade 1 to 2, and more frequent with dacomitinib. CONCLUSION Dacomitinib demonstrated significantly improved PFS versus erlotinib, with acceptable toxicity. PFS benefit was observed in most clinical and molecular subsets, notably KRAS wild-type/EGFR any status, KRAS wild-type/EGFR wild-type, and EGFR mutants.[1]

References

Randomized Phase II Study of Dacomitinib (PF-00299804), an Irreversible Pan-Human Epidermal Growth Factor Receptor Inhibitor, Versus Erlotinib in Patients With Advanced Non-Small-Cell Lung Cancer. Ramalingam, S.S., Blackhall, F., Krzakowski, M., Barrios, C.H., Park, K., Bover, I., Seog Heo, D., Rosell, R., Talbot, D.C., Frank, R., Letrent, S.P., Ruiz-Garcia, A., Taylor, I., Liang, J.Q., Campbell, A.K., O'Connell, J., Boyer, M. J. Clin. Oncol. (2012) [Pubmed]

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