Trastuzumab (T) and chemotherapy (CT) is a standard treatment in patients (pts) with HER2-positive (+) advanced breast cancer (ABC) at later lines of therapy. Lapatinib (L) and T have proven to be active in the same setting. The present study evaluated the efficacy, toxicity and quality of life (QoL) of T+L versus T + physician’s choice CT in pts with HER2+ ABC pretreated with at least two lines of anti-HER2 treatment.
In this open-label, multicenter, phase II trial, pts were randomly assigned 1:1 to receive either T+L with endocrine therapy at the physician’s discretion in case of hormone receptor positive ABC (arm A) or T+CT (arm B). The primary endpoint was the clinical benefit rate (CBR) and the secondary endpoints included overall survival (OS), progression-free survival (PFS), quality of life (QoL), and safety.
Between 2015 and 2020, 59 pts were randomized and evaluated for the present analyses. After a median (m) follow-up of 57.5 months (mo), the CBR was 20.7% (95% CI 9.4-39.3) vs 26.7% (95% CI 13.1-44.9; P= 0.76), the mOS was 29.9 mo (95% CI 19.6-NE) vs 31.1 mo (95% CI 26.1-NE; hazard ratio [HR] 1.07, 95% CI 0.57-2.0; P=0.82) and mPFS was 3.6 mo (95% CI 3.0-5.3) vs 6.1 mo (95% CI 4.0-14.3; HR 0.63, 95% CI 0.37-1.37; P=0.08) in arm A vs arm B, respectively. Any grade (G) adverse events (AEs) occurred in 86.2% and 66.7% of pts in arm A and B, respectively. The incidence of G3-4 AEs was 24.1% and 13.3% in arm A and B, respectively. The impact on QoL significantly favored arm A (P=0.03).
AEs Overall (N=59) Arm A (N=29) Arm B (N=30) Patients with at least one AE 45 (76.3) 25 (86.2) 20 (66.7) Diarrhea 14 (23.7) 11 (37.9) 3 (10) Fatigue 13 (22) 7 (24.1) 6 (20) Abdominal pain 7 (11.9) 3 (10.3) 4 (13.3) Anemia 7 (11.9) 4 (13.8) 3 (10) Neutropenia 5 (8.5) 0 (0) 5 (16.7) Nausea 5 (8.5) 3 (10.3) 2 (6.7) Thrombocytopenia 5 (8.5) 4 (13.8) 1 (3.3) Paresthesia 4 (6.8) 0 (0) 4 (13.3) Fever 3 (5.1) 3 (10.3) 0 (0) Skin disorders 3 (5.1) 3 (10.3) 0 (0)
No difference in efficacy was observed between T+L and T+CT. QoL deterioration was less frequent in pts in T+L arm though a higher number of any AEs was observed in these patients compared with those who received T+CT. Overall
EudraCT 2013-005044-29; Date when the record was first entered in the EudraCT database: 16-05-2014.
Oncotech.
Novartis, GSK.
C. De Angelis: Financial Interests, Personal, Advisory Board, Consultant fees, travel expenses: Roche, AstraZeneca, GSK; Financial Interests, Personal, Advisory Board, consultant fees, travel expenses: Lilly; Financial Interests, Personal and Institutional, Advisory Board, Honoraria, research funding, travel expenses: Novartis; Financial Interests, Personal, Advisory Board, Honoraria, travel expenses: Pfizer; Financial Interests, Personal, Advisory Board: Seagen; Financial Interests, Institutional, Funding: Daiichi Sankyo; Financial Interests, Personal, Other, Travel expenses: Celgene. M. Pagliuca: Other, Personal, Other, Travel expenses: Gilead, Pfizer. T. Gamucci: Financial Interests, Personal, Advisory Board: Seagen, Pfizer, Eisai, Daiichi Sankyo, AstraZeneca, Novartis. M. Mansutti: Financial Interests, Personal, Advisory Board: AstraZeneca, Eli Lilly, Gentili, Gilead, Novartis, Pfizer, Seagen, Roche. Z. Ballatore: Financial Interests, Personal, Other, Honoraria: Ipsen, Novartis, Roche. M. De Laurentiis: Financial Interests, Personal, Advisory Board: Roche, Novartis, Eli Lilly, Pierre Fabre, AstraZeneca, MSD, Seagen, Gilead, Daiichi Sankyo, Pfizer, Exact Science, Ipsen, Takeda, Sanofi Genzyme. R. Bordonaro: Financial Interests, Personal, Speaker’s Bureau, Honoraria, consulting or advisory role: Novartis, AstraZeneca, Sanofi, Amgen, Roche, Pfizer, Janssen-Cilag, BMS; Financial Interests, Personal, Speaker’s Bureau, Consulting or advisory role: Bayer. S. Cinieri: Financial Interests, Personal, Other: Lilly Oncology, Seagen, AstraZeneca. A. Fabi: Financial Interests, Personal, Other, Honoraria: Roche, Pfizer, Eli Lilly, Novartis, Eisai, AstraZeneca, Exact Science, Epihonpharma, Daiichi Sankyo, Gilead, Seagen. L. Del Mastro: Financial Interests, Personal, Invited Speaker, Educational meeting: Novartis, Symposia, Andromeda E20, Vyvamed srl; Financial Interests, Personal, Invited Speaker, Lecture: Ipsen; Financial Interests, Personal, Advisory Board, Her2+ and TN breast cancer: Roche; Financial Interests, Personal, Invited Speaker, Consultancy for TNBC text: Roche; Financial Interests, Personal, Advisory Board, denosumab: Amgen; Financial Interests, Personal, Advisory Board, Early and metastatic BC: Eli Lilly; Financial Interests, Personal, Invited Speaker, CDK4-6 inhibitors: Eli Lilly; Financial Interests, Personal, Advisory Board, tucatinib: Seagen Int; Financial Interests, Personal, Advisory Board, Oncotype dx: Exact sciences, Havas life; Financial Interests, Personal, Advisory Board, Neratinib: Pierre Fabre; Financial Interests, Personal, Invited Speaker, Internal training: MSD; Financial Interests, Personal, Invited Speaker, Educational meetings: Accademia Nazionale Medicina; Financial Interests, Personal, Invited Speaker, Author for BC text: Pensiero Scientifico Editore; Financial Interests, Personal, Advisory Board, Breast cancer: Uvet; Financial Interests, Personal, Other, Author slide kits and interviews: Think2it; Financial Interests, Personal, Advisory Board, Palbociclib: Pfizer; Financial Interests, Personal, Invited Speaker, Breast cancer: Aristea, Meeting SrL; Financial Interests, Personal, Other, Author slide kits: Forum service; Financial Interests, Personal, Other, Author text about biosimilars: Edizioni Minerva Medica; Financial Interests, Personal, Other, consultant: Kardo srl; Financial Interests, Personal, Invited Speaker, Breast cancer meetings: Delphi international, Over srl; Financial Interests, Personal, Invited Speaker: Prex Srl, Editree; Financial Interests, Personal, Advisory Board: Uvet, Collage SpA, Daiichi Sankyo, AstraZeneca, Agendia, Gilead; Financial Interests, Personal, Other, Interview: Infomedica srl; Financial Interests, Personal, Other, Consultant: Sharing progress in cancer care - Switzerland; Financial Interests, Personal, Other, Consultancy: Eli lilly; Financial Interests, Institutional, Funding, National coordinating PI: Roche; Financial Interests, Institutional, Funding, Local PI: AstraZeneca, Roche, Eli Lilly, Daiichi Sankyo, Novella Clinical, Novartis; Non-Financial Interests, Institutional, Product Samples, Genomic Test: FoundationOne. F. Puglisi: Financial Interests, Personal, Other, Honoraria: Amgen, Daiichi Sankyo, Celgene, Lilly, Gilead, Ipsen, MSD, Novartis, Pierre Fabre, Pfizer, Seagen, Takeda, Viatris; Financial Interests, Personal, Other, Honoraria, research funding: AstraZeneca, Eisai, Roche. S. de Placido: Financial Interests, Personal, Advisory Role: Novartis, Roche, Celgene, AstraZeneca, Amgen, Eisai, Lilly, Pfizer, Gentili. M. Giuliano: Financial Interests, Institutional, Funding: Novartis, AstraZeneca; Financial Interests, Personal, Advisory Board: AstraZeneca, Daiichi Sankyo, Exact Sciences, Lilly, MSD, Novartis, Seagen; Financial Interests, Personal, Advisory Board, Travel expenses: Pfizer, Roche; Financial Interests, Personal, Other, Travel expenses: Celgene. G. Arpino: Financial Interests, Personal, Advisory Board, Travel expenses: Roche, Pfizer, Lilly, MSD, AstraZeneca, Novartis; Financial Interests, Institutional, Funding: Roche, Pfizer, Lilly, AstraZeneca, Novartis, MSD. All other authors have declared no conflicts of interest.