Abstract 259P
Background
Breast cancer (BC) with low-level HER2 expression (HER2-low) is defined by an immunohistochemistry (IHC) score of 1+ or 2+ without HER2 gene amplification or excess gene copy number as measured by in situ hybridization (ISH). HER2-low BC may respond differently to treatment than BC with no HER2 expression (HER2-0); thus, we conducted an unplanned post hoc analysis of three randomized, pivotal phase III studies (Studies 301, 304, and 305) to compare eribulin vs other chemotherapies in patients (pts) who had MBC.
Methods
Pts enrolled had MBC and ≤2 (Study 301) or 2-5 (Studies 304, 305) prior lines of chemotherapy for advanced/recurrent/metastatic disease including an anthracycline and a taxane. Pts were treated with eribulin vs capecitabine (Study 301), vinorelbine (Study 304), or treatment of physician’s choice (TPC; Study 305). Median OS, median PFS, and ORR were analyzed, the latter two per RECIST (Studies 301, 305: v1.0; Study 304: v1.1) by independent imaging review. ORR was measured in the intent-to-treat population (Studies 301, 304) and in evaluable pts (Study 305).
Results
Eligible enrolled pts are shown in the Table; baseline characteristics were generally balanced between treatment arms in all studies; all pts in Study 304 were Chinese. PFS and OS outcomes were generally similar or improved with eribulin vs chemotherapy in pts with HER2-low and HER2-0 MBC, irrespective of study (Table); PFS and OS were generally similar among HER2-low, HER2-0, and HER2-positive pts randomized to eribulin. ORR for eribulin vs capecitabine was similar in Study 301 for HER2-low (8.8% vs 10.4%) and HER2-0 pts (10.1% vs 8.9%). ORR generally trended towards improvement with eribulin vs vinorelbine in Study 304 (HER2-low: 34.8% vs 22.4%; HER2-0: 24.5% vs 18.0%) and eribulin vs TPC in Study 305 (HER2-low: 18.8% vs 6.1%; HER2-0: 10.4% vs 4.0%). Table: 259P
| HER2 | Low | 0 | ||||
| n | OSa | PFSa | n | OSa | PFSa | |
| 301 | ||||||
| Eribulin | 114 | 15.7; 13.1-18.1 | 4.1; 2.8-5.4 | 248 | 15.9; 14.6-18.6 | 4.0; 3.0-4.3 |
| Capecitabine | 135 | 13.5; 10.3-15.9 | 3.6; 2.7-4.2 | 237 | 13.5; 11.8-15.5 | 4.0; 3.0-4.9 |
| HR | 0.9 | 1.0 | 0.8 | 1.1 | ||
| 95% CI | 0.7-1.2 | 0.7-1.4 | 0.6-<1.0 | 0.9-1.3 | ||
| 304 | ||||||
| Eribulin | 69 | 13.2; 11.4-21.1 | 4.1; 2.8-4.2 | 102 | 13.5; 9.3-17.6 | 2.8; 2.7-4.1 |
| Vinorelbine | 67 | 11.0; 9.9-16.9 | 3.2; 2.7-4.2 | 100 | 14.3; 10.6-NE | 2.7; 1.4-2.8 |
| HR | 0.9 | 0.9 | 1.1 | 0.7 | ||
| 95% CI | 0.5-1.4 | 0.6-1.3 | 0.8-1.7 | 0.5-0.9 | ||
| 305 | ||||||
| Eribulin | 121 | 12.8; 9.1-15.7 | 3.7; 3.1-4.1 | 222 | 13.8; 12.0-14.9 | 3.7; 3.1-4.9 |
| TPC | 57 | 11.0; 7.7-NE | 2.1; 1.9-3.7 | 117 | 10.2; 8.4-14.6 | 2.2; 1.9-3.3 |
| HR | 0.8 | 0.7 | 0.8 | 0.7 | ||
| 95% CI | 0.5-1.3 | 0.4-1.0 | 0.6-1.1 | 0.6-<1.0 |
aUnits: mo; 95% CI. HR, hazard ratio; NE, not estimable.
Conclusions
Eribulin had efficacy regardless of HER2 status, and, in HER2-low pts, had similar or numerically superior outcomes vs chemotherapy in each study..
Clinical trial identification
NCT00337103, NCT02225470, NCT00388726.
Editorial acknowledgement
Medical writing support was provided by Michael Venditto, PharmD, of Oxford PharmaGenesis Inc., Newtown, PA, USA.
Legal entity responsible for the study
Eisai Inc., Nutley, NJ, USA.
Funding
Eisai Inc., Nutley, NJ, USA.
Disclosure
P.A. Kaufman: Financial Interests, Personal, Stocks/Shares: Amgen; Financial Interests, Personal, Other, Honoraria: Lilly, Polyphor, Macrogenics, Eisai; Financial Interests, Personal, Advisory Role: Polyphor, Roche/Genentech, Lilly, Eisai, Macrogenics, AstraZeneca; Financial Interests, Personal, Speaker’s Bureau: Lilly; Financial Interests, Institutional, Research Grant: Polyphor, Lilly, Zymeworks, Pfizer, Sanofi. C.J. Twelves: Financial Interests, Personal, Invited Speaker, Speaker: Pfizer, Eisai; Financial Interests, Personal, Advisory Board, Member: Daiichi/AZ; Other, Other, Unpaid trustee: The UK Charity for Triple Negative Breast Cancer. A.H. Awada: Financial Interests, Personal, Advisory Board: Roche, Amgen, BMS, Pfizer, Novartis, EISAI; Financial Interests, Personal, Invited Speaker: Lilly, BMS, MSD; Non-Financial Interests, Other, Co-chair: Oncodistinct network for clinical research; Non-Financial Interests, Other, Scientific committee member: Fondation contre le cancer (Belgium; Non-Financial Interests, Other, Member: BSMO; Other, Other, Travel sponsoring for SABCS 2020: Roche; Other, Other, Travel sponsoring for ASCO 2020: Pfizer. S. Im: Financial Interests, Personal, Advisory Board, no payment: AstraZeneca, Novartis, Eisai, Roche, Hanmi, Pfizer, Lilly, MSD, GSK, Daiichi Sankyo; Financial Interests, Institutional, Research Grant: AstraZeneca, Pfizer, Roche, Eisai, Dae Woong; Financial Interests, Institutional, Invited Speaker, Clinical Trial Budget: AstraZeneca, Eisai, Hanmi, Novartis, Roche, Pfizer, Daiichi Sankyo, MSD, Lilly; Financial Interests, Institutional, Research Grant, Clinical Trial Budget: Boryung Pharm. L. Vahdat: Financial Interests, Personal, Advisory Role: Seagen, Polyphor, Osmol Therapeutics, Berg Pharma, Gilead, Depymed; Financial Interests, Personal and Institutional, Research Grant: Arvinas, Genentech, Novartis. B. Xu: Financial Interests, Personal, Advisory Board: Novartis, AstraZeneca; Financial Interests, Personal, Invited Speaker: Pfizer, Roche, Eisai; Financial Interests, Institutional, Research Grant: Henrui. W. Hauck, R. Xie, B. Lalayan: Financial Interests, Personal, Full or part-time Employment: Eisai Inc. 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, Other, Travel cost and expenses: Roche, Novartis, Eisai, Daiichi Sankyo. All other authors have declared no conflicts of interest.