Abstract PD07-04: A randomized phase II neoadjuvant trial evaluating anastrozole and fulvestrant efficiency for post-menopausal ER-positive, HER2-negative Breast Cancer patients: first results of the UNICANCER CARMINA 02 French trial
Authors: Lerebours F , Bourgier C , Alran S , Mouret-Reynier M-A , Venat Bouvet L , Kerbrat P , Salmon R , Mijonnet S , Becette V , Trassard M , Spyratos F , Lebas N , Martin A-L , Lemonnier J , Mouret-Fourme E 
Published: August 2014

Purpose: Neoadjuvant hormone therapy (HT) promotes breast-conserving surgery (BCS) and minimizes treatment-related toxicities for oestrogen receptor (ER)-positive HER2 negative breast cancer (BC). We aimed to evaluate the response rates to an AI (anastrozole) or an antioestrogen (fulvestrant) and to identify specific biomarkers of sensitivity to both treatments.

Patients and Methods: A phase II multicentre, open-label trial was conducted to evaluate the efficacy of anastrozole and fulvestrant. 116 postmenopausal patients (pts) with ER positive, HER2 negative, operable BC were recruited in 6 centers and randomly assigned to receive either neoadjuvant anastrozole (arm A; 1mg/day) or fulvestrant (arm B; 500mg, with a loading dose during first month then q4w) for 4 months (mo). Pts with a good clinical response estimated by the clinician at 4 mo were allowed to pursue treatment for 2 more mo (i.e. up to 6 mo). The primary endpoint was to evaluate the best clinical response (by palpation) by RECIST criteria at 6 mo (or 4 mo). US and MR imaging were performed at baseline, after 1 mo treatment, and before surgery. Pathological response was evaluated using Sataloff classification. Follow-up is planned for 5 yrs.

Results: Between Oct 2007 and Apr 2011, 59 pts were randomized to arm A and 57 to arm B. Main baseline characteristics were well-balanced between the 2 arms: Median age was 68 yrs-old (53–91) in arm A and 74 yrs-old (51–88) in arm B. Histological grades were EE I-II in 53 pts (89 %) and 49 pts (86%) and median clinical size before treatment was 41.5 mm and 42.3 mm in arm A and B respectively.

Neither SAE nor grade 3/4 toxicity was reported. The most common treatment-related AEs were grade1/2 hot flushes (27% and 12% of pts in arm A and B respectively), and musculoskeletal symptoms (20% and 21%).

35 pts in arm A and 29 pts in arm B continued assigned treatment up to 6 mo depending on the clinical response evaluated at 4 mo. Also, the clinical response rate was estimated at 4 mo orat 6 mo. 1 death post-surgery was reported in arm B with no proven relationship with treatment.

Overall clinical response rates (CR + PR) at 4 or 6 mo were 62% (CI 95% [49–75]) in arm A and 46% (CI 95% [32–59]) in arm B. Clinical response rate amelioration at 6 mo was observed among 15% of pts in each arm.

BCS was performed in 59% of pts in arm A and 49% in arm B. (1 pt from arm B refused surgery).

Pathological response according to Sataloff classification: TA and TB tumor responses were observed in 17/59 pts (29%) in arm A vs 12/57 (21%) in arm B respectively.

Conclusions: Both anastrozole and fulvestrant show excellent efficacy and tolerability as neoadjuvant therapy in post-menopausal pts with endocrine-dependent, HER2-negative BC.

Objective response rates and improvement in surgical outcome seem to be more frequent with anastrozole. However disease stabilization and tolerability are in favour of fulvestrant.

Our data suggest that neo-adjuvant HT improves surgical options for HR+ post-menopausal women. Correlation between clinical & pathological responses and outcome as well as the identification of markers of sensitivity to both treatments will be also studied.

Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr PD07-04.