Veliparib Beneficial in Patients with BRCA Wild Type Carcinoma

In patients with BRCA wild type (BRCAwt) carcinomas, therapy with veliparib was beneficial even at low homologous recombination deficiency (HRD) scores compared with carboplatin and paclitaxel. Additionally, HRD score was not predictive of patient outcomes for veliparib therapy versus a control, according to a study presented in conjunction with the Society of Gynecologic Oncology 2020 Annual Meeting on Women’s Cancer.

The phase 3 VELIA trial demonstrated that veliparib dosed concurrently with carboplatin and paclitaxel and continued as maintenance monotherapy resulted in significantly better progression-free survival (PFS) compared with carboplatin and paclitaxel alone in patients with newly diagnosed advanced high-grade serous ovarian carcinoma (HGSC). VELIA enrolled patients without regard to germline or somatic BRCA mutation, HRD, or platinum sensitivity, providing a unique opportunity to evaluate the prognostic and predictive role of the HRD assay, according to the study authors.

A total of 532 patients with untreated stage 3-4 HGSC received 6 cycles (21-day interval) of carboplatin and paclitaxel following primary cytoreduction or as neoadjuvant chemotherapy with interval cytoreduction. The HRD score was determined by Myriad myChoice HRD CDx assay with cutoff ≥33 for HRD-positive and <33 for non-HRD status.

Researchers randomized the participants by disease stage, timing of surgery, residual disease post primary surgery, paclitaxel schedule, geographic region, and germline BRCA status. The analysis was restricted to patients randomized to carboplatin and paclitaxel with placebo then placebo maintenance (control), and carboplatin and paclitaxel with veliparib, and then veliparib maintenance (veliparib-throughout). The correlation of HRD score with outcome was limited to patients with BRCAwt HGSC to understand the predictive power of HRD score in BRCAwt HGSC using the PFS endpoint in veliparib-throughout versus control.

Within the BRCAwt population included in the analysis, participants who were HRD positive had a PFS hazard ratio (HR) of 0.77 that favored the use of veliparib and the participants who were HRD negative had a similar PFS HR of 0.76. In comparing HRD score versus observed HR between veliparib-throughout and control, researchers could not identify a clear cutoff score to accurately determine who would benefit most from the veliparib-throughout regimen.

The researchers concluded that in patients with BRCAwt carcinomas, HRD score was not predictive of patient outcomes for veliparib-throughout versus control. Therefore, veliparib is beneficial in patients who are BRCAwt HRD positive and negative, according to the study authors.

Reference

Exploring the relationship between homologous recombination score and progression-free survival in BRCA wildtype ovarian carcinoma: Analysis of veliparib plus carboplatin/paclitaxel in the velia study. SGO website. https://sgo.confex.com/sgo/2020/meetingapp.cgi/Paper/17045. Accessed April 3, 2020.