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 (Table). Updated data for time to first or second subsequent therapy or death will be presented.
No. of events/no. of pts | 5-y Median PFS | HR (95% CI) | 5-y PFS rate,* (%) | ||||
Olaparib + bev | Pbo + bev | Olaparib + bev | Pbo + bev | Olaparib + bev | Pbo + bev | ||
ITT | 366/537 | 222/269 | 22.9 | 16.6 | 0.63 (0.53–0.74) | 29 | 16 |
HRD+ | 136/255 | 104/132 | 46.8 | 17.6 | 0.41 (0.32–0.54) | 46 | 19 |
tBRCAm | 78/157 | 58/80 | 60.7 | 21.7 | 0.45 (0.32–0.64) | 50 | 25 |
HRD+ excluding tBRCAm | 58/97 | 46/55 | 30.0 | 16.6 | 0.47 (0.32–0.70) | 41 | 15 |
HRD−/unknown | 230/282 | 118/137 | 17.3 | 16.0 | 0.90 (0.72–1.13) | 13 | 13 |
HRD− | 167/192 | 74/85 | 16.6 | 16.2 | 1.01 (0.77–1.33) | 8 | 12 |
Investigator assessed (RECIST 1.1). tBRCAm status by central labs and HRD status by Myriad MyChoice HRD Plus. |
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.
NCT02477644 (23 June 2015)
Medical writing assistance was provided by Abbie Newman BSc, at Cence, funded by AstraZeneca and Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.