Abstract
Elucidation of PARP inhibitor activity in BRCAwt recurrent ovarian cancer by hrr mutational gene profile analysis.
Author
Mansoor Raza Mirza
Nordic Society of Gynecologic Oncology (NSGO) and Rigshospitalet University Hospital, Copenhagen, Denmark
info_outline
Mansoor Raza Mirza, Bin Feng, Ming Shan, Kaiming Sun, Ilkar Yalcin, Kevin Coleman, Kenneth S. Thress, Sebastien Hazard, Jing Y. Wang, Ursula A. Matulonis
Full text
Authors
Mansoor Raza Mirza
Nordic Society of Gynecologic Oncology (NSGO) and Rigshospitalet University Hospital, Copenhagen, Denmark
info_outline
Mansoor Raza Mirza, Bin Feng, Ming Shan, Kaiming Sun, Ilkar Yalcin, Kevin Coleman, Kenneth S. Thress, Sebastien Hazard, Jing Y. Wang, Ursula A. Matulonis
Organizations
Nordic Society of Gynecologic Oncology (NSGO) and Rigshospitalet University Hospital, Copenhagen, Denmark, TESARO, Inc., Waltham, MA, Dana-Farber Cancer Institute, Boston, MA
Abstract Disclosures
Research Funding
Pharmaceutical/Biotech Company
Background:
Niraparib is an oral, selective poly(ADP-ribose) polymerase inhibitor (PARPi) approved for maintenance treatment of BRCA mutated (
BRCA
mut) and
BRCA
wild-type (
BRCA
wt) recurrent ovarian cancer patients (pts) who are in response to platinum-based chemotherapy. In the non-germline
BRCA
mutated (non-g
BRCA
mut) cohort of the ENGOT-OV16/NOVA trial, clinical benefit with niraparib vs placebo was seen in pts regardless of their Myriad myChoice HRD test status (
BRCA
mut and homologous recombination deficiency [HRD] score), with a hazard ratio (HR) of 0.38 in HRD-positive (HRDpos) and 0.58 in HRD-negative (HRDneg) pts. To determine if treatment benefit in HRDneg pts may result from mutations in other homologous recombination repair (
HRR
) genes, we examined the relationship between progression-free survival and other
HRR
gene mutations in the NOVA non-gBRCAmut cohort.
Methods:
A retrospective, exploratory biomarker analysis was conducted using all available tumor samples from 331 pts enrolled in the NOVA non-g
BRCA
mut cohort. Mutation status of
HRR
genes was evaluated using a 43-gene NGS assay (Myriad Genetics), including
BRCA1/2
and 16 additional
HRR
genes.
Results:
In this exploratory analysis of the NOVA non-g
BRCA
mut cohort, niraparib demonstrated clinical benefit in pts with somatic
BRCA
mutation (HR, 0.27) and in
BRCA
wt pts (HR, 0.47). In addition,
BRCA
wt pts with other
HRR
gene mutations also derived benefit from niraparib (HR, 0.31), as did
BRCA
wt/
HRR
wt pts (HR, 0.49). When
BRCA
wt/
HRR
wt pts were categorized by HRD score, clinical benefit was also observed in both HRDpos and HRDneg pts, with HRs of 0.33 and 0.60, respectively. These results suggest that, although these biomarkers have good positive predictive value, they are not good negative predictors for niraparib benefit in this indication.
Conclusions:
This retrospective, exploratory analysis of the ENGOT-OV16/NOVA non-g
BRCA
mut cohort suggests that although pts with somatic
BRCA
mutation and other
HRR
mutations benefit from niraparib treatment, clinical benefit is also seen in HRDneg pts without
HRR
mutations, perhaps related to other genomic, epigenetic, or functional alterations within ovarian tumors yet to be defined.