Randomized Phase II trial of nintedanib, afatinib and sequential combination in castration-resistant prostate cancer.
OBJECTIVE
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.


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.


CONCLUSIONS
Nintedanib and/or afatinib demonstrated limited anti-tumor activity in unselected advanced castration-resistant prostate cancer patients.
Drug Development Unit, Divisions of Cancer Therapeutics & Clinical Sciences, Institute of Cancer Research/Royal Marsden Hospital, Downs Road, Sutton, Surrey, UK.
L Rhoda
LR
Molife
Aurelius
A
Omlin
Rob J
RJ
Jones
Vasilios
V
Karavasilis
David
D
Bloomfield
Graeme
G
Lumsden
Peter C
PC
Fong
David
D
Olmos
Joe M
JM
O'Sullivan
Ian
I
Pedley
Tamas
T
Hickish
Peter
P
Jenkins
Emilda
E
Thompson
Nikhil
N
Oommen
Duncan
D
Wheatley
Catherine
C
Heath
Graham
G
Temple
Katy
K
Pelling
Johann S
JS
de Bono
D000077716:Afatinib; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D007211:Indoles / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D064129:Prostatic Neoplasms, Castration-Resistant / Q000188:drug therapy* / Q000473:pathology; D011799:Quinazolines / Q000008:administration & dosage; D016896:Treatment Outcome
D007211:Indoles; D011799:Quinazolines; D000077716:Afatinib; C530716:nintedanib