SAN ANTONIO – In patients with high risk breast cancer, neoadjuvant treatment, PARPi-7, BRCAness, and MP1/2 predict response to veliparib plus carboplatin therapy, a study presented at the 2016 San Antonio Breast Cancer Symposium (SABCS) has shown.1
In the multicenter, adaptively randomized, phase 2 I-SPY 2 trial (ClinicalTrials.gov Identifier: NCT01042379), which was designed to screen multiple experimental regimens in combination with standard neoadjuvant chemotherapy for breast cancer, veliparib plus carboplatin added to standard therapy led to higher rates of pathologic complete response compared with standard therapy alone in triple negative breast cancer.
To determine predictors of response to therapy, researchers evaluated biomarkers associated with mechanism of action of each investigational treatment assessed, along with predefined subsets, in I-SPY 2.
“Thirteen percent of the 114 patients were found to carry a deleterious or suspected deleterious BRCA1/2 mutation, most of which were in triple negative breast cancers,” said Denise Wolf, PhD, Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, California.
Twenty-nine percent of the 56 patients with BRCA wild-type had pathologic complete responses, while 75% of the 12 patients with BRCA1/2 mutations had them.
“BRCA1/2 germline mutation status was associated with response in the veliparib-carboplatin arm (odds ratio [OR], 7.25; P =.006), but its low prevalence in the control arm precluded further evaluation,” Dr Wolf explained.
Researchers also found that PARPi-7 was associated with pathologic complete response in the veliparib-carboplatin arm (OR, 6.8; P =.00025) but not in the control arm (OR, 0.95; P =1.0), suggesting that PARPi-7 is a specific predictor of veliparib-carboplatin response.
Investigators further determined that BRCAness and MP1/2 class were associated with response to treatment, but not CIN70 or PARP1 protein and elevated protein levels.
However, concordance between pairs of veliparib-carboplatin sensitivity biomarkers in patients with triple negative breast cancer was moderate, meaning that these signatures are not identifying the same patient. Therefore, investigators analyzed whether multiple biomarkers could be combined to assess sensitivity to treatment.
“Patients who are also MP2 and PARPi7-high are more sensitive to veliparib-carboplatin than patients with fewer markers in the ‘sensitive’ state,” noted Dr Wolf. “But the caveat is our small sample size, thus our findings need to be validated in bigger trials, and in carboplatin single treatment.”
1. Wolf D, Yau C, Sanil A, et al. DNA repair deficiency biomarkers and MammaPrint High1/(ultra)High2 risk as predictors of veliparib/carboplatin response: results from the neoadjuvant I-SPY 2 trial for high risk breast cancer. Paper presented at: 2016 San Antonio Breast Cancer Symposium; December 6-10, 2016; San Antonio, TX.