Mini Oral session

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

Speakers
  • Antonio Jose Gonzalez Martin (Madrid, Spain)
Date
Fri, 24.02.2023
Time
16:15 - 17:30
Room
Auditorium 113
Duration
5 Minutes

Abstract

Background

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.

Methods

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).

Results

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.
*Kaplan–Meier estimates.
CI, confidence interval; HR, hazard ratio; ITT, intent-to-treat.

Conclusions

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.

Clinical trial identification

NCT02477644 (23 June 2015)

Editorial acknowledgement

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.

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