Abstract 205P
Background
RIB + ET demonstrated statistically significant progression-free survival (PFS) and overall survival (OS) benefits in the ML-2, -3, and -7 trials in pts with HR+/HER2− ABC. The presence of visceral mets indicates a worse prognosis, with a particularly poor survival observed in pts with liver mets. Here we report a pooled survival analysis of the ML-2, -3, and -7 trials in pts with visceral mets, including those with liver mets.
Methods
In ML-2, postmenopausal pts were randomized 1:1 to receive first-line (1L) RIB or placebo (PBO) with letrozole. In ML-3, postmenopausal pts were randomized 2:1 to receive RIB or PBO with fulvestrant in the 1L or second-line (2L) setting. In ML-7, premenopausal pts were randomized 1:1 to receive 1L RIB or PBO and goserelin with nonsteroidal aromatase inhibitor (NSAI)/tamoxifen (only pts in the NSAI arm were included in this analysis).
Results
A significant PFS and OS benefit was observed with RIB in pts with visceral mets (Table), among which were pts with liver mets or ≥3 met disease sites across the pooled population of 1L/2L. This significant benefit persisted in the 1L subgroup, including in the subgroups of pts with a worse prognosis, such as those with liver mets or ≥3 met sites who achieved a median OS of ≈4-5 y with RIB. No new safety signals, including liver enzyme elevations, even in pts with baseline liver mets, were observed.
Conclusions
This large, pooled analysis of the ML trials confirms the consistent survival benefit of RIB + ET in pts with visceral mets who historically have a poor prognosis. This analysis also demonstrates the substantial benefit of RIB in those with poorer outcomes within the visceral mets subgroup, ie, pts with liver mets and those with multiple met disease sites, especially in the 1L population. Table: 205P
| Visceral mets | Liver mets | Visceral mets and ≥3 mets | ||||||||||
| Overall | 1L | Overall | 1L | Overall | 1L | |||||||
| ET+ | RIB | PBO | RIB | PBO | RIB | PBO | RIB | PBO | RIB | PBO | RIB | PBO |
| n | 640 | 484 | 395 | 319 | 276 | 222 | 140 | 116 | 334 | 263 | 253 | 195 |
| mPFS, mo | 22.1 | 12.7 | 29.6 | 14.7 | 13.4 | 5.7 | 16.7 | 9.8 | 21.3 | 11.0 | 24.8 | 14.5 |
| HR (95% CI), P | 0.61 (0.53-0.70), <.0001 | 0.57 (0.48-0.68), <.001 | 0.52 (0.42-0.65), <.0001 | 0.55 (0.41-0.74), <.0001 | 0.55 (0.46-0.67), <.0001 | 0.59 (0.47-0.74), <.001 | ||||||
| mOS, mo | 49.0 | 46.5 | 62.7 | 52.1 | 39.6 | 35.4 | 44.2 | 38.1 | 49.0 | 40.4 | 57.7 | 49.3 |
| HR (95% CI), P | 0.81(0.69-0.94), .003 | 0.79(0.65-0.97), .023 | 0.71(0.57-0.89), .002 | 0.77(0.55-1.07), .12 | 0.73 (0.59-0.90), .002 | 0.81 (0.63-1.03), .09 |
Clinical trial identification
NCT01958021 (ML-2) NCT02422615 (ML-3) NCT02278120 (ML-7).
Editorial acknowledgement
Medical writing support was provided by Shashank Tandon, PhD at MediTech Media, funded by Novartis Pharmaceuticals Corporation.
Legal entity responsible for the study
Novartis Pharmaceuticals Corporation.
Funding
Novartis Pharmaceuticals Corporation.
Disclosure
D.A. Yardley: Financial Interests, Institutional, Advisory Role, Consulting or Advisory Role: Genentech/Roche, NanonString Technologies, Novartis; Financial Interests, Personal, Speaker’s Bureau: Genentech/Roche, Novartis; Financial Interests, Institutional, Sponsor/Funding, Research funding (inst): Genentech/Roche, Novartis, Abbvie, AstraZeneca, Clovis Oncology, Immunomedics, InventisBio, Lilly, MedImmune, Medivation, Merck, Oncothyreon, Pfizer, Syndax, Tesaro, Daiichi-Sankyo, Eisai; Financial Interests, Personal, Other, Travel/accommodations/expenses: Genentech/Roche, Novartis; Financial Interests, Personal and Institutional, Advisory Role, Consulting or advisory role (inst): Biotheranostics, Bristol-Myers Squibb, Celgene, Daiichi Sankyo/Lilly; Financial Interests, Personal and Institutional, Advisory Role, Consulting or Advisory Role: Eisai. Y.S. Yap: Financial Interests, Personal, Advisory Board: Novartis, Pfizer, Lilly, AstraZeneca, Eisai, MSD, Inivata, Specialised Therapeutics; Financial Interests, Personal, Invited Speaker: Novartis, Pfizer, AstraZeneca, MSD, Novartis; Financial Interests, Personal, Other, Grant review: Pfizer. R.H. De Boer: Financial Interests, Personal, Advisory Board, Breast Cancer Ad Board: Gilead, AstraZeneca, Novartis, Eli Lilly; Financial Interests, Personal, Invited Speaker: Amgen, Pfizer; Financial Interests, Personal, Other, Advice on Breast cancer management: Eli Lilly; Financial Interests, Institutional, Invited Speaker, Phase III Breast Cancer trial: AstraZeneca, Pfizer. M. Campone: Financial Interests, Institutional, Research Grant, Research grants via institute: Pfizer, AstraZeneca, Sanofi, Gilead, Novartis, Lilly, Abbvie, Servier, Sandoz, Accord. A. Ring: Financial Interests, Personal, Advisory Role, Consulting or Advisory Role: Roche UK, Pfizer, Novartis, Lilly, MSD Oncology, AstraZeneca/Daiichi Sankyo, Seattle Genetics. M. De Laurentiis: Financial Interests, Personal, Invited Speaker, Speaker's Honoraria: Pfizer, Novartis, Roche, Celgene, AstraZeneca, Eisai, Eli Lilly, Amgen, Pierre Fabre; Financial Interests, Personal, Advisory Board, Advisory Board Honoraria: Pfizer, Novartis, Roche, Celgene, AstraZeneca, Eisai, Eli Lilly, Amgen, MSD, Pierre Fabre, Exact Science, Daiichi-Sankyo, Gilead, Seagen. J. O'Shaughnessy: Financial Interests, Personal, Advisory Board: Abbvie, Agendia, Amgen, Aptitude Health, AstraZeneca, Bristol-Myers Squibb, Celgene, Eisai, G1 Therapeutics, Genentech, Immunomedics, Ipsen Biopharmaceuticals, Lilly, Merck, Myriad, Novartis, Ondonate, Pfizer, Puma, Prime Oncology, Roche, Seattle Genetics, Syndax, Carrick Therapeutics, Daiichi Sankyo, Gilead Sciences, Ontada, Pierre Fabre Pharmaceuticals, Samsung Bioepis, Sanofi. J. Cortés: Financial Interests, Personal, Advisory Board: Roche, Celgene, Cellestia, AstraZeneca, Seattle Genetics, Daiichi Sankyo, Erytech, Athenex, Polyphor, Lilly, Merck Sharp& Dohme, GSK, LEUKO, Bioasis, Clovis oncology, Boehringer Ingelheim, Ellipses, Hibercell, BioInvent, Gemoab, Gilead, Menarini, Zymeworks, Reveal Genomics; Financial Interests, Personal, Invited Speaker: Roche, Novartis, Celgene, Eisai, Pfizer, Samsung Bioepis, Lilly, Merck Sharp& Dohme, Daiichi Sankyo; Financial Interests, Personal, Stocks/Shares: MedSIR, Nektar Therapeutics; Financial Interests, Institutional, Research Grant: Roche, Ariad Pharmaceuticals, AstraZeneca, Baxalta GMBH/Servier Affaires, Bayer healthcare, Eisai, Guardanth health, Merck Sharp&Dohme, Pfizer, Piqur Therapeutics, Puma B, Queen Mary University of London; Other, Travel cost and expenses: Roche, Novartis, Eisai, Daiichi Sankyo. Y. Chattar, A. Thuerigen, J.P. Zarate: Financial Interests, Personal and Institutional, Full or part-time Employment, Employment: Novartis; Financial Interests, Personal and Institutional, Stocks/Shares, Stock ownership: Novartis. A. Nusch: Financial Interests, Personal, Advisory Role, Consulting/Advisory role: Novartis; Financial Interests, Personal, Other, Travel/accommodation/expenses: Novartis; Financial Interests, Personal and Institutional, Sponsor/Funding, Research funding: Novartis; Financial Interests, Personal, Advisory Role, Consulting/Advisory Role: Amgen. All other authors have declared no conflicts of interest.