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 SS, Blackhall F, Krzakowski M, Barrios CH, Park K, Bover I, Seog Heo D, Rosell R, Talbot DC, Frank R, Letrent SP, Ruiz-Garcia A, Taylor I, Liang JQ, Campbell AK, O'Connell J, Boyer M.

Source

Suresh S. Ramalingam, Winship Cancer Institute of Emory University, Atlanta, GA; Fiona Blackhall, Christie National Health Service Foundation Trust, Manchester, United Kingdom; Denis C. Talbot, Oxford Oncology Centre, Oxford, United Kingdom; Maciej Krzakowski, The Maria Sklodowska-Curie Institute of Oncology, Warsaw; Poland; Carlos H. Barrios, PUCRS School of Medicine, Porto Alegre, Brazil; Keunchil Park, Sungkyunkwan University School of Medicine; Dae Seog Heo, Seoul National University Hospital, Seoul, Korea; Isabel Bover, Hospital Son Llatzer, Palma de Mallorca; Rafael Rosell, Catalan Institute of Oncology, Badalona, Spain; Richard Frank, Norwalk Hospital, Norwalk; Ian Taylor, Jane Q. Liang, Alicyn K. Campbell, and Joseph O'Connell, Pfizer Oncology, Groton, CT; Stephen P. Letrent and Ana Ruiz-Garcia, Pfizer Oncology, La Jolla, CA; and Michael Boyer, SydneyCancer Centre, Camperdown, Australia.

Abstract

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.

TimAllenMDJD

Wednesday, July 4, 2012