Abstract PS10-11: Associations with response to poly(ADP-ribose) polymerase (PARP) inhibitors in patients with BRCA mutated metastatic breast cancer: Results of a meta-regression analysis
Authors: Desnoyers Alexandra , Wilson Brooke E. , Nadler Michelle B. , Amir Eitan 
Published: February 2021

Background: PARP inhibitors (PARPi), when given as single agents, have modest antitumor activity in patients with advanced breast cancer and mutation in BRCA1 or BRCA2. It is unclear whether some subgroups derive greater benefit from treatment.Methods: Two electronic databases (MEDLINE, CENTRAL) and one registry (Clinicaltrials.gov) were searched from inception to June 2020 to identify trials of PARPi in patients with metastatic breast cancer. Objective response rate (ORR) and disease control rate (DCR) to PARPi were extracted and pooled in a meta-analysis using the Mantel Haenszel random effects model. Analyses were performed for patients with a BRCA mutation exclusively. Meta-regression explored the influence of patient and tumor characteristics and previous chemotherapy on ORR and DCR as reported in individual studies. Analysis comprised of a linear regression weighted by individual study sample size using the weighted least squares (mixed effect) method. Quantitative significance was defined using methods described by Burnand et al.

Results: Twenty-two studies comprising 1627 patients were identified and among these 1466 (90%) patients had a germline (n=1451) or a somatic (n=15) BRCA mutation and were included in the analysis. In 7 of these studies (32%; n=680 patients), the PARPi was given in combination with a platinum-based chemotherapy.; 54% of breast cancers were triple-negative. 81% of patients had received at least 1 prior line of chemotherapy in the metastatic setting and 28% were previously exposed to a platinum-based chemotherapy in the metastatic setting. Pooled ORR was 46%; 66% when combined with platinum vs 36% with PARPi alone (OR 3.44, 2.77-4.29, p0.001). Meta-regression results are shown in the Table. Previous chemotherapy in the metastatic setting, especially platinum-based chemotherapy, was associated with highly significantly lower ORR as defined by by Burnand et al. Age and hormone receptor status were not associated with response. Quantitatively similar results were observed for DCR. Conclusion: PARPi therapy is associated with lesser response in patients with prior chemotherapy exposure, especially platinum-based treatment. There was no association between ORR and hormone receptor status or age.

Dependent variableVariableCoefficients BêtaSignifianceORR BRCA1/2n = 146645.67 %Age-0.320.34Previous chemotherapy in metastatic setting-0.700.004Previous platinum in metastatic setting-0.620.02Platinum refractory-0.390.22Hormone receptor positive0.190.48Triple negative-0.120.66DCR BRCA1/2n = 126071.47 %Age-0.240.53Previous chemotherapy in metastatic setting-0.740.006Previous platinum-0.420.21Platinum refractory-0.070.83Hormone receptor positive-0.120.69Triple negative0.230.47

Citation Format: Alexandra Desnoyers, Brooke E. Wilson, Michelle B. Nadler, Eitan Amir. Associations with response to poly(ADP-ribose) polymerase (PARP) inhibitors in patients with BRCA mutated metastatic breast cancer: Results of a meta-regression analysis [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS10-11.