Randomized Phase II trial of nintedanib, afatinib and sequential combination in castration-resistant prostate cancer
Molife LR, Omlin A, Jones RJ, Karavasilis V, Bloomfield D, Lumsden G, Fong PC, Olmos D, O'Sullivan JM, Pedley I, Hickish T, Jenkins P, Thompson E, Oommen N, Wheatley D, Heath C, Temple G, Pelling K, de Bono JS. Future Oncol. 2014 Feb;10(2):219-31. doi: 10.2217/fon.13.250.

Author information

Drug Development Unit, Divisions of Cancer Therapeutics & Clinical Sciences, Institute of Cancer Research/Royal Marsden Hospital, Downs Road, Sutton, Surrey, UK.

Abstract

ABSTRACT Aims: The aim of this article was to evaluate afatinib (BIBW 2992), an ErbB family blocker, and nintedanib (BIBF 1120), a triple angiokinase inhibitor, in castration-resistant prostate cancer patients. Patients & methods: Patients were randomized to receive nintedanib (250 mg twice daily), afatinib (40 mg once daily [q.d.]), or alternating sequential 7-day nintedanib (250 mg twice daily) and afatinib (70 mg q.d. [Combi70]), which was reduced to 40 mg q.d. (Combi40) due to adverse events. The primary end point was progression-free rate at 12 weeks. Results: Of the 85 patients treated 46, 20, 16 and three received nintedanib, afatinib, Combi40 and Combi70, respectively. At 12 weeks, the progression-free rate was 26% (seven out of 27 patients) for nintedanib, and 0% for afatinib and Combi40 groups. Two patients had a ≥50% decline in PSA (nintedanib and the Combi40 groups). The most common drug-related adverse events were diarrhea, nausea, vomiting and lethargy. Conclusion: Nintedanib and/or afatinib demonstrated limited anti-tumor activity in unselected advanced castration-resistant prostate cancer patients.