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+ (Table). No OS benefit was seen in HRD− pts in any clinical risk subgroup (Table). 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.
| Higher risk (n=595) | Lower risk (n=211) | |||||||
| No. of events/ | 5-y OS rate† (%) | No. of events/ | 5-y OS rate† (%) | |||||
| HRD status | Ola + bev | Pbo + bev | Ola + bev | Pbo + bev | Ola + bev | Pbo + bev | Ola + bev | Pbo + bev |
| Full analysis set | 249/399 | 128/196 | 38.5 | 35.3 | 39/138 | 30/73 | 72.7 | 58.3 |
| HRD+* | 82/177 | 53/89 | 55.2 | 42.2 | 11/78 | 16/43 | 88.3 | 61.3 |
| tBRCAm | 43/109 | 29/55 | 65.2 | 48.3 | 5/48 | 8/25 | 91.4 | 66.1 |
| HRD− | 116/144 | 46/62 | 18.2 | 26.3 | 24/48 | 12/23 | 48.0 | 48.5 |
| HRD status by Myriad MyChoice HRD Plus assay; tBRCAm status by central labs. | ||||||||
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%.
NCT02477644
Medical writing assistance was provided by Helen Speedy, PhD, at Seques, funded by AstraZeneca and Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.