91MO - Randomized trial of neoadjuvant chemotherapy with or without concurrent aromatase inhibitor therapy to downstage ER+ve breast cancer: Breast Cancer Trials group ANZ 1401 ELIMINATE trial.

Background

Chemotherapy (CT) and endocrine therapy (ET) are used sequentially in systemic management of ER+ve HER2-negative early breast cancer, leading to a delay in the initiation of ET. There is little randomized data to assess the benefits/harms of concurrent chemo-endocrine therapy (CET) using aromatase inhibitors (AI). We examined neoadjuvant CT with the addition of letrozole (plus goserelin in pre-/peri-menopausal women) versus CT alone.

Methods

This randomized phase II trial included women with clinical stage 2 or 3, ER+ve HER2-negative grade 2-3 breast cancer suitable for anthracycline and taxane CT, with randomization in a 2:1 ratio to CET or CT. Primary endpoint was proportion of pathologic stage 0 or IA at surgery. The study had 80% power to rule out a 30% rate of down-staging in favour of a rate of 45% in the CET arm with 95% confidence. Pathological complete response (pCR), residual cancer burden (RCB), safety and surgical outcomes were secondary endpoints. Participants underwent pre-and post-treatment breast MRI to determine overall objective radiologic response rate. Patients were evaluable if they received 6 or more cycles of CET or CT in the absence of progression.

Results

134 women were randomized, and 122 evaluable for the primary outcome, 38% postmenopausal, 62% pre-or perimenopausal. 69% of evaluable patients were stage II, 31% stage III, 74% grade 2, 84% ductal carcinoma, mean tumour diameter was 45mm (MRI). Table: 91MO

CET showed higher rates of febrile neutropenia (11% vs 4%) but lower peripheral neuropathy (3% vs 7%).

Conclusions

The primary outcome was not met. ELIMINATE demonstrated a non-significant improvement in down-staging to pathologic stage 0 or 1A in luminal breast cancer with concurrent neoadjuvant chemotherapy and AI therapy. An additional 9% patients receiving CET reached an RCB score < 2 but BCS rates were similar in both groups.

Legal entity responsible for the study

Breast Cancer Trials - Australia and New Zealand.

Funding

Breast Cancer Trials - Australia and New Zealand National Health and Medical Research Council (Australia).

Disclosure

P. Francis: Non-Financial Interests, Personal, Funding, International Lecture Travel: Novartis, Ipsen. N. Zdenkowski: Non-Financial Interests, Personal, Advisory Board: Lilly, Eisai, AstraZeneca; Non-Financial Interests, Personal, Funding, honorarium: Roche, Pfizer, Eisai; Financial Interests, Institutional, Research Grant: Pfizer, Roche, GSK; Financial Interests, Personal, Other, Educational Funding: Roche, Novartis, Amgen. S. Loi: Financial Interests, Institutional, Expert Testimony, Consultant: Aduro Biotech, Puma Biotechnologies, Pfizer, Seattle Genetics, BMS; Financial Interests, Institutional, Advisory Board, Consultant: Novartis, GlaxoSmithKline, Roche Genentech, AstraZeneca, Silverback Therapeutics, G1 Therapeutics; Financial Interests, Institutional, Funding, Research: Novartis, BMS, Merck, Puma Biotechnology, Eli Lilly, Nektar Therapeutics, AstraZeneca, Seattle Genetics, Roche-Genentech; Non-Financial Interests, Advisory Role, Consultant (Non remunerated): Seattle Genetics, Novartis, Bristol Myers Squibb, Merck, AstraZeneca, Roche Genentech. J. Lombard: Non-Financial Interests, Personal, Advisory Board: GSK, AstraZeneca. A. Spillane: Non-Financial Interests, Personal, Invited Speaker, Honoraria: Stryker, Lilly; Non-Financial Interests, Personal, Advisory Board: Q-Biotics. All other authors have declared no conflicts of interest.