Everolimus as treatment for breast cancer patients with bone metastases only: results of the phase II RADAR study.
OBJECTIVE
Everolimus has shown to stop formation and activity of osteoclasts. Breast cancer patients with bone metastases only are candidates for effective but low toxic treatment.


METHODS
We evaluated everolimus in a double-blind, placebo-controlled, phase II, randomized discontinuation study in breast cancer patients with HER2 negative breast cancer patients with bone metastases only. After being stable on 8 weeks of everolimus 10 mg/day, patients were randomized to everolimus-continuation or placebo. Primary outcome was time (from randomization) to progression (TTP). Seventy-six patients would have had to be randomized to show a hazard ration (HR) of 0.5 for everolimus-continuation.


RESULTS
Eighty-nine patients were enrolled in 4 years. Thirty-nine patients with SD after 8 weeks on everolimus were randomized to everolimus-continuation or placebo. TTP in patients with everolimus-continuation was 37.0 (95 % CI 16.7-40.3) versus 12.6 weeks (95 % CI 7.1-17.9) with placebo [HR 0.554 (95 % CI 0.282-1.09) p = 0.0818], adjusted for endocrine therapy [HR 0.464 (95 % CI 0.226-0.954) p = 0.037]. TTP in everolimus responders (n = 6) was 86 weeks.


CONCLUSIONS
The RADAR study is mainly hypothesis generating. It suggests that everolimus has single-agent activity, and patients with bone metastases only may retrieve long-term benefit from everolimus if they do not progress within 8 weeks of treatment.
Universitätsfrauenklinik Aachen, Aachen, Germany.
Nicolai
N
Maass
Nadia
N
Harbeck
Christoph
C
Mundhenke
Christian
C
Lerchenmüller
Jana
J
Barinoff
Hans-Joachim
HJ
Lück
Johannes
J
Ettl
Bahriye
B
Aktas
Sherko
S
Kümmel
Siegfried
S
Rösel
Steffen
S
Wagner
Lothar
L
Müller
Joachim
J
Bischoff
Kristina
K
Lübbe
Kathrin
K
Schwedler
Marcus
M
Schmidt
Dirk
D
Bauerschlag
Valentina
V
Nekljudova
Gunter
G
von Minckwitz
Sibylle
S
Loibl
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000556:secondary*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology*; D018450:Disease Progression; D004311:Double-Blind Method; D064420:Drug-Related Side Effects and Adverse Reactions / Q000453:epidemiology; D000068338:Everolimus; D005260:Female; D006801:Humans; D008875:Middle Aged; D010919:Placebos; D020123:Sirolimus / Q000031:analogs & derivatives* / Q000627:therapeutic use
D000970:Antineoplastic Agents; D010919:Placebos; D000068338:Everolimus; D020123:Sirolimus