Abstract 577P
Background
The iPocc randomised multicentre international study reported improved progression-free survival (PFS) but not overall survival (OS) with IP carboplatin and IV paclitaxel vs IV chemotherapy (chemo) in patients (pts) with epithelial ovarian, fallopian tube or primary peritoneal cancer. Previous studies suggested that pts with BRCA-deficient tumours may benefit from IP chemo. We conducted a non-prespecified analysis of the prognostic and predictive value of HRD in tissue samples retrospectively obtained from iPocc trial pts.
Methods
166 pts from participating centres in Singapore and Japan had adequate tissue for next-generation sequencing with ACT Genomics ACTOnco®+. HRD was defined by high loss of heterozygosity at a threshold of >=0.35 (LOH high) or presence of a pathogenic BRCA mutation (BRCAmt). Median PFS and OS were estimated using Kaplan-Meier method. Fisher’s exact and Student’s t-test were used to compare group characteristics.
Results
Both IP and IV arms had similar frequencies of BRCAmt, homologous recombination repair pathway mutations (HRRmt) and LOH high. All BRCAmt tumours were LOH high. There were no differences in PFS or OS in IP vs IV arms in this cohort. Outcome data based on HRD subgroups are summarised in the table. In the overall group, LOH high was associated with improved OS (HR 0.43, p=.001) but not PFS (HR 1.04, p=.87). BRCAmt pts showed a trend towards improved OS (HR 0.68, p=.24) and PFS (HR 0.73, p=.32). HRRmt status did not significantly affect OS (HR 0.95, p=.84) or PFS (HR 1.21, p=.30). Table: 577P
Outcomes of IP vs IV arms based on BRCA, HRR and HRD (based on LOH >= 0.35) status
| IP vs IV chemo | |||||||
| Frequency | Median PFS (months) | HR | p | Median OS (months) | HR | p | |
| BRCAmt | n=16 (9.6%) | 25.7 vs 23.8 | 0.83 | .73 | 94.5 vs 85.3 | 0.90 | .90 |
| BRCAwt | n=150 (90.4%) | 22.1 vs 22.8 | 1.07 | .72 | 60.1 vs 77.1 | 1.18 | .44 |
| LOH high | n=135 (81.3%) | 23.5 vs 23.4 | 1.00 | .98 | 73.0 vs 85.3 | 1.21 | .42 |
| LOH low | n=31 (18.7%) | 9.2 vs 17.2 | 1.20 | .71 | 29.4 vs 33.2 | 1.00 | .996 |
| HRRmt | n=109 (65.7%) | 20.7 vs 23.3 | 1.15 | .50 | 65.8 vs 85.3 | 1.25 | .39 |
| HRRwt | n=57 (34.3%) | 25.0 vs 20.1 | 0.98 | .95 | 57.2 vs 65.2 | 1.09 | .81 |
Conclusions
In this small subgroup analysis of iPocc pts, BRCAmt pts demonstrated a trend towards improved PFS and OS with IP compared with IV chemo. BRCAmt and LOH high, but not HRRmt, correlated with improved outcomes in the overall group. Larger prospective studies with integrated molecular analyses are needed to better define the impact of HRD in IP vs IV chemo.
Clinical trial identification
NCT01506856 / GOTIC-001 / JGOG3019
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
A. Yabuno: Other, Personal and Institutional, Other, Honoraria: Takeda, AstraZeneca, Eisai. All other authors have declared no conflicts of interest.