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36MO Maintenance olaparib plus bevacizumab (bev) in patients (pts) with newly diagnosed advanced ovarian cancer (OC): 5-year (y) progression-free survival (PFS) by molecular subgroup in the PAOLA-1/ENGOT-ov25 trial

Year: 2023

Type: article

Abstract: The first-line setting represents the only opportunity for cure in advanced OC. 5-y PFS rates may predict cure as most pts not relapsing at 5 years are potentially cured. In the final overall survival (OS) analysis of the Phase III PAOLA-1/ENGOT-ov25 trial (NCT02477644), maintenance olaparib + bev provided a clinically meaningful OS benefit vs placebo (pbo) + bev in pts with newly diagnosed advanced OC who tested positive for homologous recombination deficiency (HRD+; tumour BRCA1/2 mutation [tBRCAm] and/or genomic instability) regardless of tBRCAm status (Ray-Coquard et al. Ann Oncol 2022:LBA29). We evaluated 5-y PFS by molecular subgroup to help inform the potential for cure. Pts in response after platinum-based chemotherapy + bev were randomized 2:1 to olaparib (300 mg bid for up to 24 months) + bev (15 mg/kg q3w for up to 15 months) or pbo + bev. A post hoc, updated descriptive PFS analysis by molecular subgroup was conducted at the final OS data cutoff (DCO). 537 pts were randomized to olaparib + bev and 269 to pbo + bev (median PFS follow-up in censored pts was 56.7 and 57.8 months, respectively). At DCO (22 March 2022), the 5-y PFS rate was 46% with olaparib + bev vs 19% with pbo + bev in the HRD+ group, 50% vs 25%, respectively, in the tBRCAm group, 41% vs 15%, respectively, in the HRD+ excluding tBRCAm group, 13% vs 13%, respectively, in the HRD−/unknown group, and 8% vs 12%, respectively, in the HRD− group. Updated data for time to first or second subsequent therapy or death will be presented.Table: 36MONo. of events/no. of pts5-y Median PFSHR (95% CI)5-y PFS rate,* (%)Olaparib + bevPbo + bevOlaparib + bevPbo + bevOlaparib + bevPbo + bevITT366/537222/26922.916.60.63 (0.53–0.74)2916HRD+136/255104/13246.817.60.41 (0.32–0.54)4619tBRCAm78/15758/8060.721.70.45 (0.32–0.64)5025HRD+ excluding tBRCAm58/9746/5530.016.60.47 (0.32–0.70)4115HRD−/unknown230/282118/13717.316.00.90 (0.72–1.13)1313HRD−167/19274/8516.616.21.01 (0.77–1.33)812Investigator assessed (RECIST 1.1). tBRCAm status by central labs and HRD status by Myriad MyChoice HRD Plus.*Kaplan–Meier estimates.CI, confidence interval; HR, hazard ratio; ITT, intent-to-treat. Open table in a new tab Investigator assessed (RECIST 1.1). tBRCAm status by central labs and HRD status by Myriad MyChoice HRD Plus. *Kaplan–Meier estimates. CI, confidence interval; HR, hazard ratio; ITT, intent-to-treat. The 5-y updated descriptive PFS rates suggest the benefit of adding olaparib to bev is sustained beyond end of treatment and may indicate the potential of cure in HRD+ newly diagnosed advanced OC, supporting use of maintenance olaparib + bev as a standard of care in pts with HRD+ tumours, regardless of tBRCAm status.

Source: ESMO Open

DOI: 10.1016/j.esmoop.2023.100816