| Autor: |
Okamoto, Aikou, Fleming, Gini F, Bookman, Michael A, Brady, M.F., Swisher, Elizabeth M, Dahl Steffensen, Karina, Cloven, Noelle G, Enomoto, T, Dinh, Minh H, Coleman, Robert L, Aghajanian, Carol |
| Jazyk: |
angličtina |
| Rok vydání: |
2020 |
| Zdroj: |
Okamoto, A, Fleming, G F, Bookman, M A, Brady, M F, Swisher, E M, Dahl Steffensen, K, Cloven, N G, Enomoto, T, Dinh, M H, Coleman, R L & Aghajanian, C 2020, ' Veliparib with carboplatin and paclitaxel in frontline high-grade serous ovarian cancer (HGSOC): Efficacy and safety of paclitaxel weekly and every 3 weeks in the VELIA study ', Annals of Oncology, vol. 31, no. Suppl. 4, 818P, pp. S618 . https://doi.org/10.1016/j.annonc.2020.08.957 |
| Popis: |
BackgroundThe phase III randomised VELIA study (NCT02470585) demonstrated significantly improved progression-free survival (PFS) with carboplatin/paclitaxel (CP) and veliparib (VEL) induction therapy followed by VEL maintenance vs CP alone (HR 0.44; 95% CI 0.28–0.68; Coleman et al., N Engl J Med 2019). Investigators chose between IV P 175 mg/m2 every 3 weeks (Q3W), or 80 mg/m2 dose-dense (DD) weekly. This exploratory analysis evaluated PFS and safety by P regimen.MethodsPatients received (1:1:1) CP + placebo followed by placebo maintenance (CP alone), or CP + VEL followed by placebo (VEL combination only), or CP + VEL followed by VEL (VEL throughout). Randomisation was stratified by P regimen and residual disease, disease stage, and region. Combination therapy was given for six 21-day cycles, followed by 30 cycles of VEL/placebo maintenance monotherapy. PFS was analysed using a Cox proportional hazards regression model.ResultsAmong evaluable patients (N=1132), 52% received DD P; 48% received Q3W P. Cohorts were balanced for clinical characteristics and molecular signature (BRCA, homologous repair deficiency [HRD]). Median dose intensity ranged from 95%−99% with Q3W P and 84%−94% with DD P across treatment arms. Overall, DD P demonstrated longer PFS vs Q3W P (median: 20.5 vs 15.7 months; hazard ratio [HR] 0.77; 95% CI 0.66–0.89). The table shows effects of P regimen across subgroups and treatment arms. PFS was improved with VEL throughout vs CP alone, irrespective of P regimen. In the as-treated safety population (N=1124), Grade 3/4 adverse events were more frequent with DD P vs Q3W P, with rates of 90% vs 63% with CP alone, 94% vs 80% with VEL combination only, and 94% vs 82% with VEL throughout.ConclusionsIn this exploratory analysis, DD P (+/- VEL) was associated with longer PFS overall and in biomarker-negative subgroups, and more frequent Grade 3/4 haematologic toxicities vs Q3W P in patients with newly diagnosed HGSOC.Clinical trial identificationNCT02470585. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
|
