T-DM1 is standard treatment in patients (pts) with HER2-positive breast cancer with residual disease after neoadjuvant therapy. The GIM26-TRASTHER study of the Gruppo Italiano Mammella (GIM) study group collects data from the Italian compassionate use program that anticipated drug reimbursement.
Inclusion criteria mirrored the Katherine trial. We registered adverse events (AEs) that were considered to be certainly/probably/possibly related to T-DM1 as per investigators’ judgement. We used descriptive analysis for data presentation.
202 pts were included in 18 centers between Sep 2021 and Dec 2022. Median age was 52 years (IQR 45-59), 30% of the pts (n=61) were premenopausal and 56% (n=113) had at least 1 comorbidity (main: thyroid disorders 13%, hypertension 13%, dyslipidemia 4.5%). Smoking status was available for 156 pts, and 39 (25%) were current or former smokers. As neoadjuvant therapy, 85 % of the pts (n=169) received anthracycline plus taxane chemotherapy and 25 % (n=50) dual anti-HER2 blockade. Overall, 320 T-DM1-related AEs of any grade were registered in 105 pts (52%). G3 AEs were observed in 11 pts (5.4%), while there were no G4-G5 AEs. Most prevalent AEs of any grade were transaminases increase (19.8%), thrombocytopenia (15.3%), nausea and vomiting (13.3%), fatigue (10.9%), myalgia and arthralgia (7.4%), peripheral neuropathy (6.4%) and neutropenia (5%). For 42 out of 202 pts (20.8%), T-DM1 was reduced in dose, delayed or discontinued due to toxicity. Pts experiencing any grade AEs were older (54 vs 51, p=0.046), more frequently current or former smokers (34% vs 16.6%, p=0.034), and were less exposed to anthracyclines (79% vs 92%, p=0.012) as compared to those with no AEs. No impact of menopausal status, pre-existing comorbidities and type of neoadjuvant anti-HER2 therapy was observed.
In this multicentric Italian study, no new safety concerns of adjuvant T-DM1 were observed. Toxicity seems to be mostly linked by patient’s characteristics, underlying the importance of evaluating safety profile of anticancer drugs in a real-world setting in less selected pts. Further analyses, including survival outcomes, are ongoing.
GIM (Gruppo Italiano Mammella).
Roche.
F. Poggio: Financial Interests, Personal, Invited Speaker: Eli Lilly, Novartis, Pfizer; Financial Interests, Personal, Advisory Role: AstraZeneca; Financial Interests, Personal, Other: Daiichi Sankyo, Gilead. M. Tagliamento: Financial Interests, Personal, Other, travel grants: Roche, Bristol Myers Squibb; Financial Interests, Personal, Other: AstraZeneca; Financial Interests, Personal, Writing Engagements: Novartis, MSD, Amgen. M. De Laurentiis: Financial Interests, Personal, Advisory Board: Roche, Eli Lilly, Novartis, AstraZeneca, Seattle Genetics, Gilead, Ipsen, Takeda; Financial Interests, Personal, Research Grant: Puma Biotechnology, Macrogenics, Bristol Myers Squibb. A. Gennari: Financial Interests, Personal, Invited Speaker: Eisai, Novartis, Roche, Eli Lilly, Daiichi Sankyo, Gilead. M. Lambertini: Financial Interests, Personal, Advisory Board: Roche, Novartis, Eli Lilly, AstraZeneca, Gilead, MSD, Exact Science, Seattle Genetics; Financial Interests, Personal, Speaker’s Bureau: Takeda, Knight Terapeutics, Ipsen, Sandoz, Libbs; Financial Interests, Institutional, Research Grant: Gilead. 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. All other authors have declared no conflicts of interest.