Research Spotlight: Effectiveness of PARP inhibitor maintenance therapy in ovarian cancer by BRCA1/2 and a scar-based HRD signature in real-world practice
Richardson DL, Quintanilha JCF, Danziger N, et al. Effectiveness of PARP inhibitor maintenance therapy in ovarian cancer by BRCA1/2 and a scar-based HRD signature in real-world practice. Clin Cancer Res. 2024. https://doi.org/10.1158/1078-0432.CCR-24-1225
Background:
The use of PARP inhibitors as maintenance therapy (mPARPi) after platinum-based chemotherapy is now one of the standard-of-care options for treating advanced ovarian cancer. Since maintenance therapy may be administered over a prolonged period of time, patients and physicians must carefully evaluate the potential benefits with the potential adverse effects of taking a mPARPi. Debate remains over the use of mPARPi in those without somatic or germline BRCA1/2 alterations, high genomic loss of heterozygosity (gLOH), or homologous repair deficiency (HRD).
Study details:
In this study, researchers leveraged real-world, de-identified data from the Flatiron Health-Foundation Medicine Clinico-Genomic Database to compare the effectiveness of mPARPi in real-world practice by BRCA1/2 alteration status and two genomic scar signatures, Foundation Medicine’s HRD signature (HRDsig) and gLOH. Real-world progression-free survival (rwPFS) and real-world overall survival (rwOS) were compared by biomarker status between patients who received mPARPi versus those who received no maintenance therapy.
The analysis included 673 patients, of which 160 received mPARPi, and 513 received no maintenance therapy. HRDsig-positive patients who received mPARPi had favorable rwPFS and numerically favorable rwOS compared to those with no maintenance therapy. Meanwhile, for HRDsig-negative patients, no difference in rwPFS and rwOS was observed between those who received mPARPi or no maintenance therapy. Among patients with no BRCA1/2 alterations, favorable rwPFS on mPARPi was observed with HRDsig positivity, while no difference was observed for those who were HRDsig negative.
Why this matters:
HRDsig offers a new approach to identifying patients who may benefit from mPARPi, even among patients with no BRCA1/2 alterations. About 21% of patients in the study had no BRCA1/2 alterations but were HRDsig positive, indicating they may benefit from mPARPi. Additionally, HRDsig-negative patients showed similar progression-free survival and overall survival whether they received mPARPi or no maintenance therapy, suggesting these patients may be spared unnecessary side effects and financial costs associated with mPARPi, ultimately improving a patient’s quality of life.
Finally, results between Foundation Medicine’s HRDsig and gLOH were highly concordant. However, because gLOH assessment requires higher tumor purity, it can only be assessed on a limited number of patients. Within ovarian cancer, Foundation Medicine’s HRDsig was able to be assessed on 22% more patients than gLOH. Whereas gLOH was validated for ovarian cancer only, Foundation Medicine’s HRDsig biomarker was trained on pan-solid tumor samples to enable broader application in clinical settings.
View the full publication in Clinical Cancer Research.