Messaggi chiave
- È stata condotta un’analisi esplorativa aggregata dei dati di DESTINY-Breast01/-02/-03 al fine di caratterizzare l’efficacia e la sicurezza di trastuzumab deruxtecan (T-DXd) rispetto al trattamento di confronto nei pazienti con carcinoma mammario metastatico (mBC) HER2+ che presentavano metastasi cerebrali (BM) (classificate in base al precedente trattamento locale) al basale dei rispettivi studi.
- Centoquarantotto pazienti trattati con T-DXd e 83 controlli presentavano BM al basale. Nella coorte T-DXd, il tasso di risposta obiettiva intracranica è stato del 45,2 e 45,5% in presenza di BM stabili/trattate e attive/non trattate, rispettivamente, con un tempo mediano alla risposta intracranica di 2,8 e 1,5 mesi e una durata mediana della risposta di 12,3 e 17,5 mesi. Le mediane di sopravvivenza libera da progressione nel SNC e sopravvivenza globale (OS) sono risultate pari a 12,3 mesi e non raggiunta nei pazienti con BM stabili/trattate e a 18,5 e 30,2 mesi in caso di BM attive/non trattate. Eventi avversi emergenti dal trattamento di grado ≥3 sono stati osservati nel 43,2 e 46,4% dei pazienti con e senza BM trattati con T-DXd.
- L’efficacia intracranica e il beneficio clinico in OS emersi dall’analisi, insieme alla gestibilità del profilo di sicurezza del farmaco, supportano l’uso di T-DXd in pazienti con mBC HER2+ e secondarismi cerebrali, sia stabili che in fase attiva.
Abstract
Background
- This exploratory pooled analysis investigated the efficacy and safety of trastuzumab deruxtecan (T-DXd) versus comparator treatment in patients with HER2-positive metastatic breast cancer (mBC) with brain metastases (BMs) at baseline, categorized according to previous local treatment.
Patients and methods
T-DXd data were pooled from DESTINY-Breast01/-02/-03.
Comparator data, from patients receiving physician’s choice therapy and trastuzumab emtansine, were pooled from DESTINY-Breast02 and -03, respectively.
Baseline BM status was assessed according to US Food and Drug Administration criteria.
Endpoints included intracranial objective response rate (ORR; complete or partial response in brain) per blinded independent central review (BICR) by RECIST v1.1, time to intracranial response, intracranial duration of response (DoR), central nervous system progression-free survival (CNS-PFS) by BICR, overall survival (OS), and safety.
Results
- 148 patients who received T-DXd and 83 patients who received comparator treatment had BMs at baseline.
- In those who were treated with T-DXd, the intracranial ORR of patients with treated/stable and untreated/active BMs was 45.2% and 45.5%, respectively.
- The median (range) time to intracranial response was 2.8 months (1.1-13.9 months) and 1.5 months (1.2-13.7 months) in patients with treated/stable and untreated/active BMs, respectively.
- For those with treated/stable BMs, the median (95% CI) intracranial DoR was 12.3 months (9.1-17.9 months), and for those with untreated/active BMs it was 17.5 months (13.6-31.6 months).
- The median (95% CI) CNS-PFS and OS was 12.3 months (11.1-13.8 months) and not reached (22.1 months-not estimable [NE]) in those with treated/stable BMs, and 18.5 months (13.6-23.3 months) and 30.2 months (21.3 months-NE) in those with untreated/active BMs, respectively.
- Drug-related TEAEs grade ≥3 were experienced by 43.2% of patients with BMs and 46.4% without BMs with T-DXd.
Conclusions
- T-DXd demonstrated meaningful intracranial efficacy and clinical benefit in OS, with an acceptable and manageable safety profile in patients with HER2-positive mBC with treated/stable and untreated/active BMs.