Randomized phase 2 neoadjuvant trial evaluating anastrozole and fulvestrant efficacy for postmenopausal, estrogen receptor-positive, human epidermal growth factor receptor 2-negative breast cancer patients: Results of the UNICANCER CARMINA 02 French trial (UCBG 0609).
BACKGROUND
Treatment strategies for locally advanced breast cancer in elderly patients too frail to receive neoadjuvant chemotherapy and the introduction of new classes of drugs in the early 2000s have led to the consideration of endocrine therapy as a neoadjuvant treatment for younger hormone receptor (HR)-positive, postmenopausal patients not eligible for primary breast-conserving surgery (BCS).


METHODS
This was a multicenter, phase 2, randomized trial designed to evaluate as its primary objective the clinical response rate after up to 6 months of neoadjuvant endocrine therapy (NET) alone in HR-positive/human epidermal growth factor receptor 2 (HER2)-negative patients with 1 mg of anastrozole (arm A) or 500 mg of fulvestrant (arm B). Secondary objectives included the BCS rate, tumor response assessment (breast ultrasound and magnetic resonance imaging), pathological response (Sataloff classification), safety profile, relapse-free survival (RFS), and predictive markers of responses and outcomes.


RESULTS
From October 2007 to April 2011, 116 women (mean age, 71.6 years) with operable infiltrating breast adenocarcinoma (T2-T4, N0-N3, M0) were randomized to receive anastrozole or fulvestrant. The clinical response rates at 6 months were 52.6% (95% confidence interval [CI], 41%-64%) in arm A and 36.8% (95% CI, 25%-49%) in arm B. BCS was performed for 57.6% of arm A patients and 50% of arm B patients. The RFS rates at 3 years were 94.9% in arm A and 91.2% in arm B. The Preoperative Endocrine Prognostic Index status was significantly predictive of RFS. Both treatments were well tolerated.


CONCLUSIONS
Both drugs are effective and well tolerated as NET in postmenopausal women with HR-positive/HER2-negative breast cancer. NET could be considered a treatment option in this subpopulation. Cancer 2016;122:3032-3040. © 2016 American Cancer Society.
Curie Institute, Saint-Cloud, France. florence.lerebours@curie.fr.
Florence
F
Lerebours
Gustave Roussy Institute, Villejuif, France.
Sofia
S
Rivera
Jean Perrin Center, Clermont Ferrand, France.
Marie-Ange
MA
Mouret-Reynier
Curie Institute, Paris, France.
Severine
S
Alran
Hospital and University Center, Limoges, France.
Laurence
L
Venat-Bouvet
Eugene Marquis Center, Rennes, France.
Pierre
P
Kerbrat
Curie Institute, Paris, France.
Remy
R
Salmon
Curie Institute, Saint-Cloud, France.
Veronique
V
Becette
Gustave Roussy Institute, Villejuif, France.
Céline
C
Bourgier
Curie Institute, Saint-Cloud, France.
Pascal
P
Cherel
Jean Perrin Center, Clermont Ferrand, France.
Véronique
V
Boussion
Gustave Roussy Institute, Villejuif, France.
Corinne
C
Balleyguier
Curie Institute, Paris, France.
Fabienne
F
Thibault
Hospital and University Center, Limoges, France.
Sandrine
S
Lavau-Denes
Jean Perrin Center, Clermont Ferrand, France.
Jean-Marc
JM
Nabholz
Curie Institute, Paris, France.
Brigitte
B
Sigal
Curie Institute, Saint-Cloud, France.
Martine
M
Trassard
Gustave Roussy Institute, Villejuif, France.
Marie-Christine
MC
Mathieu
R&D UNICANCER, UCBG, Paris, France.
Anne-Laure
AL
Martin
R&D UNICANCER, UCBG, Paris, France.
Jerome
J
Lemonnier
Curie Institute, Saint-Cloud, France.
Emmanuelle
E
Mouret-Fourme
D000368:Aged; D000369:Aged, 80 and over; D000077384:Anastrozole; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D018275:Carcinoma, Lobular / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D004958:Estradiol / Q000008:administration & dosage / Q000031:analogs & derivatives; D005260:Female; D005500:Follow-Up Studies; D005602:France; D000077267:Fulvestrant; D006801:Humans; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009367:Neoplasm Staging; D009570:Nitriles / Q000008:administration & dosage; D017698:Postmenopause; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D015996:Survival Rate; D014230:Triazoles / Q000008:administration & dosage
D000077384:Anastrozole; D004958:Estradiol; D000077267:Fulvestrant; D009570:Nitriles; D018719:Erb-b2 Receptor Tyrosine Kinases; D014230:Triazoles; C508053:ERBB2 protein, human
anastrozole; breast cancer; breast-conserving surgery; clinical response; fulvestrant; hormone receptor-positive; neoadjuvant endocrine therapy; phase 2; postmenopausal; survival