Messaggi chiave
- Trastuzumab deruxtecan (T-DXd) ha dimostrato un’efficacia senza precedenti in pazienti con carcinoma mammario metastatico (mBC) HER2+ pretrattate. Tuttavia, si dispone di pochi dati circa l’efficacia della molecola nella pratica clinica di routine. Nel tentativo di colmare tale lacuna, è stato condotto uno studio multicentrico retrospettivo volto a valutare efficacia e sicurezza di T-DXd in una popolazione real world.
- Sono state incluse 143 pazienti trattate con T-DXd – prevalentemente in terza linea (29%) o successiva (57%) – presso 12 centri italiani. A un follow-up mediano di 12 mesi, la sopravvivenza libera da progressione (PFS) mediana è risultata pari a 16 mesi, con tassi di PFS dell’84, 59 e 39% a 6, 12 e 18 mesi, rispettivamente. Tossicità gravi sono emerse nel 18% delle pazienti, più frequentemente neutropenia, nausea/vomito e malattia polmonare interstiziale. In 37 pazienti si è resa necessaria una riduzione di dose, senza effetti sugli esiti di risposta e sopravvivenza.
- Il presente studio conferma l’efficacia e la tollerabilità del trattamento con T-DXd in una popolazione real-world non selezionata di pazienti con mBC HER2+. I risultati sono coerenti con i dati già pubblicati. Non sono emersi nuovi segnali di sicurezza.
Abstract
Background
- Trastuzumab deruxtecan (T-DXd) demonstrated unprecedented efficacy in patients with pretreated HER2+ metastatic breast cancer (mBC). However, few data are available about its efficacy in routine clinical practice.
- In this multicenter retrospective study, we examined effectiveness and safety of T-DXd in a real-world population.
Methods
- Clinico-pathological information about patients with HER2+ mBC who received T-DXd were collected from 12 Italian hospitals. HER2 status was determined locally.
- Patients who received at least one administration of T-DXd, as any therapy line for advanced disease were included in the analysis.
- The primary endpoint was real-word PFS (rwPFS).
Results
- One hundred and forty-three patients were included. Median age was 66 (range: 37-90), and 4 men were included. Hormone receptor (HR) status was positive in 108 (75%) patients and negative in 35(25%).
- T-DXd was administered as first, second, third, or subsequent lines in 4 (3%), 16 (11%), 42 (29%), and 81 (57%) patients, respectively. Among 123 patients with measurable disease, the ORR was 68%, and the DCR was 93% (9 CRs, 74 PRs, and 30 SD). Nine (7%) patients had a primary resistance to T-DXd.
- With a median follow-up of 12 months, the median rwPFS was 16 months. RwPFS was 84%, 59%, and 39% at 6, 12, and 18 months, respectively. A favorable trend in rwPFS was reported in patients receiving T-DXd as I/II line versus further lines (17 vs. 15 months; p = 0.098). Any-grade toxicity was registered in 84 patients (59%).
- Most common adverse events (AEs) reported were nausea (33%), neutropenia (21%), and asthenia (21%). Liver toxicity and diarrhea were uncommon (5% and 1%). Severe toxicities was registered in 18% of patients, and the most frequent were neutropenia, nausea/vomiting, and ILD observed in 15, 2, and 3 patients. AEs led to dose reduction in 37 patients (26%). Dose reduction and AEs do not affect patients’ response and survival outcomes.
Conclusions
- Efficacy and safety of T-DXd were confirmed in an unselected real-world population of HER2+ mBC. These results are consistent with the results of known findings, and no new safety concerns were reported.