109O - Adjuvant endocrine therapy for premenopausal invasive lobular carcinoma (ILC): Results from SOFT and TEXT phase III studies

Background

Data from BIG1-98 along with pre-clinical findings point to a partial resistance to tamoxifen (T) among postmenopausal women diagnosed with ILC.

Methods

The TEXT and SOFT trials assigned premenopausal women with hormone receptor-positive (ER+) tumors to exemestane plus ovarian function suppression (E+OFS) or T + OFS, or to T alone in SOFT only. This analysis includes centrally reviewed ER+HER2-negative tumors (n=4115) classified as invasive ductal carcinoma (IDC), (n=3370) or ILC (n=345). Cox model analyses stratified by trial and chemotherapy use included histological subtype, treatment, and interaction term. A pre-specified level of significance P-interaction<0.2 was selected to retain statistical power (>80%). The analyses were adjusted by age, tumor size, nodal status, and centrally assessed Ki67 to define Luminal A-like (LA), (Ki67 < 14%) and LB-like tumors (Ki67 ≥ 14%). The primary endpoint was breast cancer free interval (BCFI).

Results

At 12-yr of median follow-up in the SOFT trial, E+OFS showed a larger treatment benefit over T in ILC (HR=0.32; 95%CI 0.12-0.91) than in IDC (HR=0.71; 95%CI 0.54-0.93), Pinteraction=0.15. Differences were less marked for T+OFS vs. T, ILC (HR=0.66 95%CI 0.31-1.42) and IDC HR=0.81 95%CI 0.63-1.05), Pinteraction=0.62. In SOFT+TEXT at 13-yrs, E+OFS vs. T+OFS consistently benefited ILC (HR=0.60 95%CI 0.31-1.15) and IDC (HR=0.70 [95%CI 0.58-0.85), Pinteraction=0.65. The table below shows consistent benefit E+OFS vs T or T+OFS for both LA and LB-like ILC tumors. In contrast LB-like IDC benefitted more from E+OFS vs. T+OFS, with LA-like IDC showing a much smaller benefit. Table: 109O

Conclusions

The benefits favoring OFS+E appeared to be greater for ILC when compared to IDC, overall and consistent within subgroups of LA- and LB-like tumors defined by Ki-67. E+OFS stands out as the most effective treatment for ILC.

Clinical trial identification

NCT00066690; NCT00066703.

Legal entity responsible for the study

International Breast Cancer Study Group, a division of ETOP IBCSG PartnersFoundation, sponsored the SOFT and TEXT clinical trials.

Funding

Maor Foundation.

Disclosure

J. Huober: Financial Interests, Personal, Advisory Role, Consulting: Lilly, Novartis, Roche, Pfizer, AstraZeneca, Gilead, Daiichi; Financial Interests, Personal, Other, Honoraria: Lilly, Novartis, Roche, Pfizer, AstraZeneca, Seagen, Gilead, Daiichi; Financial Interests, Institutional, Funding, Research funding: Lilly; Financial Interests, Personal, Other, Travel expenses: Roche, Daiichi, Gilead. G.F. Fleming: Financial Interests, Institutional, Principal Investigator: Roche, Iovance, Sermonix, Compugen, Corcept, AstraZeneca, Astellas, K group beta, Pfizer, Artios, Blueprint. P.A. Francis: Financial Interests, Personal, Invited Speaker, Lecture on pregnancy/fertility: Eli Lilly; Non-Financial Interests, Other, Editorial Board Member: Nature Partner Journals (npj) Breast Cancer; Non-Financial Interests, Member, American Society of Clinical Oncology: ASCO; Non-Financial Interests, Member, Medical Oncology Group of Australia: MOGA. B.A. Walley: Financial Interests, Personal, Stocks/Shares: Pfizer. S. Loi: Financial Interests, Institutional, Expert Testimony, Consultant: Aduro Biotech, Pfizer, Seattle Genetics; Financial Interests, Institutional, Advisory Board, Consultant: Novartis, GSK, Roche Genentech, AstraZeneca, Silverback Therapeutics, G1 Therapeutics; Financial Interests, Institutional, Expert Testimony, COnsultant: PUMA Biotechnologies, BMS; Financial Interests, Institutional, Expert Testimony, consultant: Gilead Therapeutics, Daiichi Sankyo, Merck, Amunix, Tallac Therapeutics, Eli Lilly; 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; Non-Financial Interests, Advisory Role, consultant (not compensated): Eli Lilly, Pfizer, Gilead Therapeutics. M.A. Colleoni: Financial Interests, Institutional, Research Grant: Roche; Non-Financial Interests, Leadership Role, CO-Chair Scientific Committee: INTERNATIONAL BREAST CANCER STUDY GROUP. B.J.K. Thuerlimann: Financial Interests, Personal, Expert Testimony: Gilead; Financial Interests, Personal, Advisory Board: pagetherapeutics; Financial Interests, Personal, Other, Expert Consultant Oncology: Innomedica; Financial Interests, Personal, Other, Expert Consultant: Enzymmanagement; Financial Interests, Personal, Invited Speaker, Med. education activities St. Gallen Breast Cancer Conference&Consensus: Medplus Honkong; Financial Interests, Personal, Member of Board of Directors: KFS, RTFCCR; Financial Interests, Personal, Other, Member QA Committee: donna-sg; Financial Interests, Personal, Other, Speaker in med. education activities St. Gallen Breast Cancer Conference&Consensus: Medplus Honkong; Financial Interests, Personal, Other, Co-Chair: SG Oncology Conferences; Financial Interests, Personal, Stocks/Shares: Novartis, Roche, Merck, Alcon, Sandoz, Innomedica, Organon; Non-Financial Interests, Member of Board of Directors: Hospiz St. Gallen. G. Viale: Financial Interests, Personal, Advisory Board: AstraZeneca, Daiichi Sankyo, MSD Oncology, Pfizer, Roche; Financial Interests, Personal, Other, Consultant: Agilent; Financial Interests, Institutional, Principal Investigator, Coordinating PI: AstraZeneca; Financial Interests, Institutional, Research Grant: Roche; Non-Financial Interests, Advisory Role: Medscape. M.M. Regan: Financial Interests, Personal, Advisory Board, Also invited speaker: Bristol Myers Squibb; Financial Interests, Personal, Advisory Board, Includes consulting: Tolmar Pharmaceuticals; Financial Interests, Personal, Advisory Board: AstraZeneca, Tersera Therapeutics; Financial Interests, Institutional, Research Grant: Bristol Myers Squibb, Bayer; Financial Interests, Institutional, Other, Director of IBCSG Statistical and Data Management Center for IBCSG investigator-initiated clinical trial supported by company: Novartis; Financial Interests, Institutional, Other, Director of IBCSG Statistical and Data Management Center for IBCSG investigator-initiated clinical trials supported by company: Pfizer, Ipsen, TerSera; Financial Interests, Institutional, Other, Director of IBCSG Statistical and Data Management Center for IBCSG investigator-initiated clinical trial drug supply from company: Roche; Financial Interests, Institutional, Other, Director of IBCSG Statistical and Data Management Center for IBCSG investigator-initiated clinical trials supported or drug supply from company: AstraZeneca; Financial Interests, Institutional, Other, Director of IBCSG Statistical and Data Management Center for IBCSG investigator-initiated clinical trials with funding from company: Debiopharm; Financial Interests, Institutional, Funding, IBCSG translational research collaboration: Biotheranostics; Non-Financial Interests, Advisory Role: Bristol Myers Squibb. All other authors have declared no conflicts of interest.