Messaggi chiave
- Vengono presentati i risultati di efficacia finali di BROCADE3, uno studio multicentrico di fase 3, randomizzato, in doppio cieco, che ha confrontato carboplatino-paclitaxel ± veliparib, un inibitore di PARP, in pazienti con carcinoma mammario avanzato HER2-, BRCA1/2-mutato, già sottoposte a un massimo di 2 linee di chemioterapia per malattia metastatica.
- Alla data iniziale di cut-off dei dati, il trattamento sperimentale aveva dimostrato un miglioramento statisticamente significativo degli esiti di sopravvivenza libera da progressione rispetto ai controlli. Tuttavia, dopo un follow-up di altri 3 anni circa, tale miglioramento non si è tradotto in un beneficio in sopravvivenza globale (mediana, 32,4 vs 28,2 mesi; hazard ratio, 0,916 [IC 95%, 0,736-1,140]; p = 0,434).
- Le lunghe sopravvivenze osservate in entrambi i bracci suggeriscono che la combinazione carboplatino-paclitaxel sia sufficiente a garantire un beneficio clinico nella popolazione descritta.
Abstract
Background
- In the BROCADE3 study, the addition of veliparib to carboplatin plus paclitaxel resulted in a significant improvement in progression-free survival (PFS) compared with placebo plus carboplatin and paclitaxel, in patients with germline BRCA1 or BRCA2 (BRCA1/2)-mutated, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer. We now report final overall survival (OS) data.
Methods
- BROCADE3 is a randomized phase 3 study that enrolled patients with BRCA1/2-mutated, HER2-negative advanced breast cancer who received ≤ 2 prior lines of chemotherapy for metastatic disease.
- Patients were randomized 2:1 to carboplatin and paclitaxel, dosed with either veliparib or matching placebo.
- OS was a secondary endpoint.
Results
- In the intention-to-treat population (N = 509), 337 patients were randomized to receive veliparib and 172 to placebo.
- Median OS was 32.4 months vs 28.2 months (hazard ratio, 0.916; 95% CI, 0.736-1.140; P = 0.434).
- The updated safety data for veliparib are consistent with those reported in the primary analysis; the addition of veliparib was generally well tolerated.
Conclusions
- Final OS data indicate that the PFS improvement shown in the primary analysis did not translate into an OS benefit.
- The long survival times observed in both arms suggest that combination therapy with paclitaxel and carboplatin provides clinical benefit in the population of patients with BRCA1/2-mutated metastatic breast cancer.