342P - Fulvestrant (FUL) plus enzastaurin (ENZA) vs FUL plus placebo (PBO) in aromatase inhibitor (AI)-resistant metastatic breast cancer (mBC): a randomiz...

Date 29 September 2012
Event ESMO Congress 2012
Session Poster presentation I
Topics Anti-Cancer Agents & Biologic Therapy
Breast Cancer, Metastatic
Presenter Robert S. De Jong
Authors R.S. De Jong1, G.S. Sonke2, N. Maass3, K. Mansouri4, L. Cirri5, P. Shi6, O. Hamid6, G. Mariani7
  • 1Department Of Internal Medicine, Martini Hospital, NL-9700 RM - Groningen/NL
  • 2Department Of Medical Oncology, Netherlands Cancer Institute - Antoni van Leeuwenhoek, Amsterdam/NL
  • 3Department Of Gynecology And Obstetrics, University Hospital Aachen, Aachen/DE
  • 4Oncology, Lilly Deutschland GmbH, Bad Homburg/DE
  • 5Oncology, Eli Lilly and Company Italia SPA, Florence/IT
  • 6Clinical Oncology, Eli Lilly and Company, Indianapolis/US
  • 7Department Of Medical Oncology, Fondazione IRCCS - Istituto Nazionale dei Tumori, Milan/IT


AIs are used as first-line treatment for postmenopausal women with hormone-receptor-positive MBC. Overexpression of PKC α has been linked to AI resistance in several studies. We examined whether Enza, a serine/threonine kinase inhibitor that targets PKC, could improve the effect of Ful in pts who progressed following first-line AI treatment for MBC.

Postmenopausal pts with hormone-receptor-positive, HER2-negative, locally advanced or MBC who progressed on prior AI received a loading dose of Ful 500 mg IM on Day (D) 1 and 250 mg on D 15 of Cycle (C) 1 and D 1 of each cycle thereafter. Enza 500 mg or PBO was administered orally once daily (QD) or 250 mg twice daily (BID). Primary endpoint was the clinical benefit rate (CBR). Secondary endpoints were response rate (RR), duration of CB, progression-free survival (PFS) and safety. A total of 156 pts was randomly assigned to therapy; 152 received at least 1 dose of study drug (39 BID; 55 QD; 58 PBO). Baseline disease characteristics were balanced across arms. There was no statistically significant difference in CBR between pts in Ful + Enza vs Ful + PBO. There was no statistically significant difference in CBRs, RRs and PFS between pts on QD and BID dosing schedules. Pts on BID dosing had numerically more TEAEs vs those on QD and PBO (61.5%, 43.6%, and 46.6%, respectively) and numerically more Grade 3/4 TEAEs vs QD and PBO (17.9%, 9.1%, and 5.2%, respectively). Most frequent Grade 3/4 TEAEs in the BID arm were fatigue (n [%]) (4 [10.3%]), dyspnea (2 [5.1%]) and nausea (2 [5.1%]).

8 pts died; 5 due to disease, 3 due to AEs: 1 drug-related hepatic dysfunction (Enza QD arm), 1 non-drug-related myocardial infarction and 1 non-drug-related respiratory failure (both in the Enza BID arm).

Ful + Enza [QD + BID] N = 94 Ful + PBO N = 58 P-value vs PBO
CBRNumber of responders,n (%), (95% CI) 41 (43.6)(33.4, 54.2) 24 (44.8) (31.7, 58.5) 0.62
RR, % (95% CI) 5.3 (1.7, 12.0) 5.2 (1.1, 14.4) 0.64
PFS, months (95% CI) 5.2 (3.5, 7.4) 5.5 (3.8, 7.4) 0.59
Median duration of CB, months 9.6 9.7 0.86

CBR = complete response + partial response + stable disease Addition of Enza to Ful does not improve disease outcome in pts with locally advanced or MBC after progression on AI.


K. Mansouri: K. Mansouri is an employees of Eli Lilly and Co.

L. Cirri: L. Cirri is an employees of Eli Lilly and Co.

P. Shi: P. Shi is an employees of Eli Lilly and Co.

O. Hamid: O. Hamid is an mployees of Eli Lilly and Co.

All other authors have declared no conflicts of interest.