[P5-19-02] Everolimus in combination with exemestane in hormone receptor-positive locally
advanced or metastatic breast cancer (BC) patients progressing on prior non-steroidal AI (NSAIs):
Ballet study (CRAD001YIC04)
Jerusalem G, Mariani G, Ciruelos EM, Martin M, Tjan-Heijnen VCG, Neven P, Gavila Gregori J,
Michelotti A, Montemurro F, Lang I, Mardiak J, Naume B, Camozzi M, Lorizzo K, Brenski D, Conte P.
CHU Sart Tilman Liege and Liege University, Liege, Belgium; Fondazione IRCCS Instituto Nazionale
dei Tumori, Milan, Italy; University Hospital 12 de Octubre, Madrid, Spain; Hospital General
Universitario Gregorio Marañón, Madrid, Spain; Maastricht University Medical Centre, Maastricht,
Netherlands; KU Leuven and University Hospital Leuven, Leuven, Belgium; Fundacion Instituto
Valenciano de Oncologia, Valencia, Spain; Azienda Ospedaliera Universitaria Pisana, Santa Chiara
Hospital, Pisa, Pisa, Italy; Fondazione del Piemonte per l'Oncologia, Institute of Candiolo Cancer
Center (IRCCs), Candiolo (Torino), Italy; National Institute of Oncology, Budapest, Hungary;
National Cancer Institute, Bratislava, Slovakia (Slovak Republic); Oslo University Hospital and
Norwa and K.G. Jebsen Center for Breast Cancer Research, Institute for Clinical Medicine, University
of Oslo, Oslo, Norway; Novartis Farma S.p.A., Origgio/VA, Italy; Istituto Oncologico Veneto IRCCS
and Università di Padova, Padova, Italy
Background:
Despite progress, a large number of breast cancer patients experience metastatic relapse and death.
Hyperactivation of the mTOR pathway has been observed in patients (pts) with BC progressing on
endocrine therapy. The BOLERO-2* trial demonstrated significant doubling of PFS obtained via dual
blockade with everolimus (EVE) and exemestane (EXE), versus EXE alone in pts refractory to NSAIs.
Methods:
BALLET is a European multi-center open-label, single-arm, expanded-access study to evaluate the
safety of EVE (10 mg/day) and EXE (25 mg/day) in postmenopausal women with hormone receptorpositive HER2 negative locally advanced or metastatic BC progressing on prior NSAIs. Study
treatment continued until disease progression, unacceptable toxicity, death, drug locally reimbursed,
discontinuation from the study for any other reason or last patient last visit (June 30th, 2014),
whichever occurred first. Here we report an ad hoc-analysis that includes all pts recruited from May
12th 2012 till Dec 31st 2013 with cut-off date March 17th 2014 (final database will be available on
October 31st 2014).
Results:
2.133 pts were recruited in 269 sites across 14 European countries. Baseline characteristics were
median age: 64 yrs; PS (ECOG) 0/1/2: 64%/30%/3%; median time from first diagnosis: 8 yrs; Stage IV
pts: 99%. At the data cut off, a total of 1795 pts (84%) had discontinued the treatment. Reasons for
discontinuation were: disease progression (38%), drug reimbursement (35%), adverse events (15 %),
consent withdrawn (4%), death (1.5%) and others (6.5%). EVE and EXE were administered as first line
treatment in 10% of pts, as second line in 23%, as third line in 22% and as fourth line or beyond in
45% of pts. 74% of pts received more than 1 line of chemotherapy in the metastatic setting. 80% of
pts experienced at least one adverse event (AE) referred by the investigators as related to EVE [45%
stomatitis, 7% non-infectious pneumonitis (NIP)]. The most frequent grade 3-4 drug related AEs were
stomatitis (8.9%), asthenia (3.2%), GGT increase (2.4%), hyperglycemia (2.4%), and NIP (1.8%).The
median time to onset of stomatitis and NIP was 3-4 weeks and 2-3 months respectively.
Conclusions:
These results confirm that the combination of EVE + EXE is a tolerable treatment in a real world
setting even in pts more heavily pretreated by chemotherapy compared to BOLERO 2. The better
understanding of side effects leading to treatment discontinuation in this large European study
where investigators frequently administered the drug for the first time, will allow defining priority
actions for better management of side effects including patient education and early interventions.
Longer follow up with mature data (expected in October 2014) will give additional information on the
safety profile, stratified by line of treatment.
* Everolimus in Postmenopausal Hormone- Receptor–Positive Advanced Breast Cancer. J. Baselga et
al, NEJM 2012.
Friday, December 12, 2014 5:00 PM