Messaggi chiave
- DESTINY-Breast06 è uno studio di fase III, randomizzato, in aperto, volto a confrontare l’efficacia e la sicurezza di trastuzumab deruxtecan rispetto alla chemioterapia a scelta del medico in pazienti con carcinoma mammario metastatico (mBC) HR+ HER2-low o ultralow già sottoposti ad almeno una linea di terapia endocrina (ET), ma naïve alla chemioterapia.
- Degli 866 pazienti randomizzati, 713 e 153 presentavano una malattia HER2-low e HER2-ultralow, rispettivamente. All’interno della coorte HER2-low, la sopravvivenza libera da progressione mediana è stata di 13,2 vs 8,1 mesi nel braccio sperimentale rispetto ai controlli (hazard ratio di progressione o morte, 0,62; IC 95%, 0,51-0,74; p <0,001). Risultati paragonabili sono stati ottenuti nella coorte esplorativa HER2-ultralow. I dati di sopravvivenza globali erano immaturi al momento dell’analisi. Eventi avversi di grado ≥3 sono stati osservati nel 52,8% dei pazienti nel braccio trastuzumab deruxtecan e nel 44,4% dei controlli, con una frequenza di eventi di malattia polmonare interstiziale (ILD)/polmonite dell’11,3 vs 0,2%, rispettivamente.
- Alla luce del beneficio in efficacia emerso dallo studio, trastuzumab deruxtecan potrebbe diventare la nuova terapia standard di cura in pazienti con mBC HR+ HER2-low e ultralow già sottoposti a ET, ma naïve alla chemioterapia. Non sono emersi nuovi segnali di sicurezza; tuttavia, la ILD rimane un rischio importante del trattamento.
Abstract
Background
- Outcomes in patients with hormone receptor-positive metastatic breast cancer worsen after one or more lines of endocrine-based therapy.
- Trastuzumab deruxtecan has shown efficacy in patients with metastatic breast cancer with low expression of human epidermal growth factor receptor 2 (HER2) after previous chemotherapy.
Methods
- We conducted a phase 3, multicenter, open-label trial involving patients with hormone receptor-positive metastatic breast cancer with low HER2 expression (a score of 1+ or 2+ on immunohistochemical [IHC] analysis and negative results on in situ hybridization) or ultralow HER2 expression (IHC 0 with membrane staining) who had received one or more lines of endocrine-based therapy and no previous chemotherapy for metastatic breast cancer.
- Patients were randomly assigned in a 1:1 ratio to receive trastuzumab deruxtecan or the physician’s choice of chemotherapy.
- The primary end point was progression-free survival (according to blinded independent central review) among the patients with HER2-low disease. Secondary end points included progression-free survival among all the patients who had undergone randomization, overall survival, and safety.
Results
- Of the 866 patients who underwent randomization, 713 had HER2-low disease, and 153 had HER2-ultralow disease.
- Among the patients with HER2-low disease, the median progression-free survival was 13.2 months (95% confidence interval [CI], 11.4 to 15.2) in the trastuzumab deruxtecan group and 8.1 months (95% CI, 7.0 to 9.0) in the chemotherapy group (hazard ratio for disease progression or death, 0.62; 95% CI, 0.51 to 0.74; p <0.001); the results were consistent in the exploratory HER2-ultralow population.
- Data for overall survival were immature.
- Adverse events of grade 3 or higher occurred in 52.8% of the patients in the trastuzumab deruxtecan group and in 44.4% of those in the chemotherapy group.
- Adjudicated interstitial lung disease or pneumonitis occurred in 49 patients (11.3%; three events were grade 5 in severity) and in 1 patient (0.2%; grade 2), respectively.
Conclusions
- Among patients with hormone receptor-positive, HER2-low or HER2-ultralow metastatic breast cancer who had received one or more lines of endocrine-based therapy, treatment with trastuzumab deruxtecan resulted in longer progression-free survival than chemotherapy.
- No new safety signals were identified.
- (Funded by AstraZeneca and Daiichi Sankyo; DESTINY-Breast06 ClinicalTrials.gov number, NCT04494425).