Background

In ML-2, RIB + LET demonstrated statistically significant overall survival (OS) vs placebo (PBO) + LET (median [m], 63.9 vs 51.4 mo) in postmenopausal pts with HR+/HER2− advanced breast cancer (ABC). Pts in ML-2 were in the 1L (no prior endocrine tx for ABC). Prior (neo)adjuvant tx was allowed; however, for pts treated with a prior nonsteroidal aromatase inhibitor, a treatment-free interval (TFI; time from end of [neo]adjuvant tx to disease recurrence) > 12 mo was required. Here we present a subgroup analysis of pts in ML-2 with de novo metastatic disease and late recurrence (TFI > 12 mo from end of any [neo]adjuvant tx).

Methods

Pts in ML-2 were randomized 1:1 to 1L LET + RIB or PBO. Pts with de novo disease or late recurrence were analyzed for OS, progression-free survival (PFS), time to chemotherapy (TTC), and chemotherapy-free survival (CFS).

Results

Of 668 pts, 18.4% had TFI ≤ 12 mo and were excluded from the analysis. A total of 545 pts were analyzed; 41.7% had de novo disease and 58.3% had late recurrence. Among pts with late recurrence, mTFI was 52.8 mo; 271/318 (85.2%) had a disease-free interval (DFI; time from initial diagnosis to disease recurrence) > 5 y and 148/318 (46.5%) had a DFI > 10 y. Baseline characteristics, including percentage of pts with de novo disease and late recurrence (Table), were balanced between arms. mOS with RIB vs PBO was 69.2 vs 54.3 mo (HR, 0.75 [0.60-0.93]; P = .005). TTC (m, 54.1 vs 40.9 mo; P = .004) and CFS (m, 42.5 vs 36.1 mo; P = .002) both favored RIB vs PBO. Additional efficacy outcomes are shown in the table. No new safety signals were observed.

Conclusions

This exploratory analysis of ML-2, which excluded pts with TFI ≤ 12 mo (known poorer prognosis in 1L), demonstrated an OS HR consistent with that for the overall population. mOS surpassed that in the overall population (RIB, 69.2 mo vs PBO, 54.3 mo: an ≈15-mo improvement with 1L RIB over PBO).

Table: 196P

Clinical trial identification

NCT01958021.

Editorial acknowledgement

Medical writing support was provided by Daniele Cary at MediTech Media, funded by Novartis Pharmaceuticals Corporation.

Legal entity responsible for the study

Novartis Pharmaceuticals Corporation.

Funding

Novartis Pharmaceuticals Corporation.

Disclosure

J. O'Shaughnessy: Financial Interests, Personal, Advisory Board: AbbVie, Agendia, Amgen, Aptitude, AstraZeneca, Bristol Myers Squibb, Celgene, Eisai, G1 Therapeutics, Genentech, Immunome, Ipsen Biopharmaceuticals, Lilly, Merck, Myriad, Novartis, Odonate Therapeutics, Pfizer, Puma, Prime, Roche, Seattle Genetics, Syndax, Carrick Therapeutics, Daiichi Sankyo, Gilead Sciences, Ontada, Pierre Fabre, Samsung, Sanofi. T. Beck: Financial Interests, Institutional, Research Grant, Institutional funding for doing research.: AbbVie, Alliance, Argenx, Ascentage Pharma Group, AstraZeneca, Biodesix, Bio-Thera, Bristol Myers Squibb, Celgene, Eli Lilly, Genentech-Roche, Hutchison, Immunomedics, Gilead, MT GroupMerck, Nektar, Pfizer, Polynoma, Seattle Genetics, Serono-EMD, Tesaro, TG Therapeutics, Daiichi - Sankyo, Exact Sciences, Boehringer - Ingleheim, Laekna, Novocure, Mirati Therapeutics, Tarveda Therapeutics, Sumitomo Dainippon Pharma Oncology (formerly Boston Bio), Elpiscience Biopharma, Takeda, Vaccinex, Vincerx Pharma, Ultimovacs, Mersana. S. Chia: Financial Interests, Personal, Advisory Board: Novartis, Pfizer, Hoffman LaRoche, Eli Lilly; Financial Interests, Institutional, Research Grant, My institution received funds for participation in clinical trials by Novartis: Novartis; Financial Interests, Institutional, Research Grant, My institution received funds for participation in clinical trials by Pfizer: Pfizer; Financial Interests, Institutional, Research Grant, My institution received funds for participation in clinical trials by Hoffman LaRoche: Hoffman LaRoche; Financial Interests, Institutional, Research Grant, My institution received funds for participation in clinical trials by Eli Lilly: Eli Lilly. C. Isaacs: Financial Interests, Personal, Advisory Board: Genentech, PUMA, Seagen, AstraZeneca, Novartis, Gilead; Financial Interests, Personal, Other, Honoraria: Pfizer, ION, Novartis; Financial Interests, Personal, Royalties: Wolters Kluwer (UptoDate), McGraw Hill (Goodman and Gillman); Financial Interests, Institutional, Research Grant, Research support to institution: Tesaro/GSK, Seattle Genetics, Pfizer, AZ, BMS, Genentech, Novartis Medical Director SideOutFoundation (non-profit). M. De Laurentiis: Financial Interests, Personal, Speaker’s Bureau, Honoraria: Pfizer, Novartis, Roche, AstraZeneca, Eisai, Eli Lilly, Pierre Fabre, Daiichi Sankyo, Menarini, Gilead, Seagen, GSK; Financial Interests, Personal, Advisory Board, Honoraria: Pfizer, Novartis, Roche, AstraZeneca, Eisai, Eli Lilly, MSD, Pierre Fabre, Daiichi Sankyo, Menarini, Gilead, Seagen, GSK. S. Kuemmel: Financial Interests, Personal, Advisory Board: Amgen, AstraZeneca, Celgene, Daiichi Sankyo, Lilly, MSD, Novartis, Seagen, Pfizer, Roche, Somatex, Gilead, Sanofi; Financial Interests, Personal, Invited Speaker: ExactScience, pfm medical, MSD, Lilly, Gilead, Roche, Sanofi, Daiichi Sankyo; Financial Interests, Personal, Ownership Interest, Minority Ownership: WSG Study Group; Financial Interests, Personal and Institutional, Invited Speaker: Roche, Novartis; Financial Interests, Institutional, Invited Speaker: Roche, Novartis, Lilly, Somatex, AstraZeneca, MSD. K. Jhaveri: Financial Interests, Personal, Advisory Board, Consultant/Advisory Board: Novartis, AstraZeneca, Pfizer, BMS, Jounce Therapeutics, Taiho Oncology, Genentech/Roche, Lilly Pharmaceuticals/Loxo Oncology, AbbVie, Eisai, Blueprint Medicines, Seattle Genetics, Daiichi Sankyo, Gilead, Olema Pharmaceuticals, Sun Pharma Advanced Research Company Ltd., Menarini/Stemline; Financial Interests, Institutional, Funding, Research funding: Novartis, AstraZeneca, Pfizer, Genentech/Roche, Lilly Pharmaceuticals/Loxo Oncology, Gilead, Debio Pharmaceuticals, Zymeworks, PUMA Biotechnology, Merck Pharmaceuticals, Context Therapeutics. W. Janni: Financial Interests, Personal, Advisory Board: Amgen, AstraZeneca, Daiichi Sankyo, Lilly, MSD, Novartis, Pfizer, Roche, Seagen, Gilead; Financial Interests, Personal, Invited Speaker: Amgen, AstraZeneca, Daiichi Sankyo, Lilly, MSD, Novartis, Pfizer, Roche, Seagen, Gilead; Financial Interests, Personal, Full or part-time Employment: Universitätsklinikum Ulm; Financial Interests, Institutional, Invited Speaker: Novartis, GSK, Sanofi, Amgen, Roche, Lilly; Non-Financial Interests, Leadership Role: Chair of AGO Breast Council. H.S. Rugo: Financial Interests, Institutional, Research Grant: Plexxikon, Macrogenics, OBI Pharma, Eisai, Pfizer, Novartis, Eli Lilly, GlaxoSmithKline, Genentech, Celsion, Merck; Financial Interests, Personal, Other, Travel, Accomodations, and Expenses: Novartis, Roche/Genentech, OBI Pharma, Bayer, Pfizer; Financial Interests, Personal, Speaker’s Bureau: Genomic Health. A. Lteif: Financial Interests, Personal and Institutional, Full or part-time Employment: Novartis; Financial Interests, Personal, Stocks/Shares: Novartis. G. Sopher: Financial Interests, Personal and Institutional, Full or part-time Employment: Novartis; Financial Interests, Personal, Stocks/Shares: Novartis. H. Hu: Financial Interests, Personal and Institutional, Full or part-time Employment: Novartis; Financial Interests, Personal, Stocks/Shares: Novartis. All other authors have declared no conflicts of interest.