32O 5-year (y) overall survival (OS) with maintenance olaparib (ola) plus bevacizumab (bev) by clinical risk in patients (pts) with newly diagnosed advanced ovarian cancer (AOC) in the phase III PAOLA-1/ENGOT-ov25 trial

In the PAOLA-1/ENGOT-ov25 trial, adding maintenance ola to bev improved progression-free survival in homologous recombination deficiency-positive (HRD+; tumour BRCA1/2 mutation [tBRCAm] and/or genomic instability) pts with newly diagnosed AOC at higher and lower risk of progression by disease stage and surgical status. Greatest benefits were seen in lower-risk pts (Harter et al. Gynecol Oncol 2022). Here, we analysed 5-y OS according to clinical risk and HRD status. Pts in response after first-line platinum-based chemotherapy + bev were randomized 2:1 to ola (300 mg bid; up to 24 months [mo]) + bev (15 mg/kg q3w; up to 15 mo) or placebo [pbo] + bev. This post hoc exploratory analysis evaluated OS in pts classified as higher risk (stage III with upfront surgery and residual disease or neoadjuvant chemotherapy; stage IV) or lower risk (stage III with upfront surgery and no residual disease), and by HRD status. 537 pts were randomized to ola + bev and 269 to pbo + bev (median OS follow-up 61.7 and 61.9 mo, respectively). Of 806 randomized pts, 595 (74%) were classified as higher risk and 211 (26%) as lower risk. At final data cutoff (22 March 2022), OS events had occurred in 377 higher-risk pts (data maturity 63%) and 69 lower-risk pts (data maturity 33%). OS was prolonged with ola + bev in higher- and lower-risk pts with a tBRCAm or who were HRD+. No OS benefit was seen in HRD− pts in any clinical risk subgroup. Subsequent PARP inhibitor therapy was received by 19.5% and 19.6% of ola + bev pts, and 45.9% and 45.2% of pbo + bev pts, in higher- and lower-risk groups, respectively.Table: 32OHRD statusHigher risk (n=595)Lower risk (n=211)No. of events/no. of pts (%)5-y OS rate† (%)No. of events/no. of pts (%)5-y OS rate† (%)Ola + bevPbo + bevOla + bevPbo + bevOla + bevPbo + bevOla + bevPbo + bevFull analysis set249/399 (62)128/196 (65)38.535.339/138 (28)30/73 (41)72.758.3HRD+*82/177 (46)53/89 (60)55.242.211/78 (14)16/43 (37)88.361.3tBRCAm43/109 (39)29/55 (53)65.248.35/48 (10)8/25 (32)91.466.1HRD−116/144 (81)46/62 (74)18.226.324/48 (50)12/23 (52)48.048.5HRD status by Myriad MyChoice HRD Plus assay; tBRCAm status by central labs.*HRD+ defined as a tBRCAm and/or genomic instability score of ≥42 on the Myriad MyChoice HRD Plus assay; †Kaplan–Meier estimates. Open table in a new tab HRD status by Myriad MyChoice HRD Plus assay; tBRCAm status by central labs. *HRD+ defined as a tBRCAm and/or genomic instability score of ≥42 on the Myriad MyChoice HRD Plus assay; †Kaplan–Meier estimates. This post hoc analysis of 5-y OS suggests that adding maintenance ola to bev should be considered for all HRD+ pts with newly diagnosed AOC, irrespective of their clinical risk status. Particular benefit was observed in HRD+ lower-risk pts who achieved 5-y OS rates of 88.3%.