Homologous Recombination Deficiency Not Predictive of Patient Outcomes for Veliparib Plus Carboplatin/Paclitaxel Therapy

Homologous recombination deficiency (HRD) is not predictive of patient outcomes for veliparib-throughout versus control in patients with BRAC wildtype (BRACwt) ovarian carcinomas. However, veliparib was found to be beneficial when added with carboplatin and paclitaxel, according to findings presented at the Society of Gynecologic Oncology 2020 Annual Meeting on Women’s Cancer.

According to the study results, 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 mutations (BRCAm), HRD, or platinum sensitivity, providing a unique opportunity to evaluate the prognostic and predictive role of the HRD assay.

A total of 523 patients with untreated stage 3/4 HGSC received 6 cycles of carboplatin and paclitaxel following primary cytoeduction or as a neoadjuvant chemotherapy with interval cytoeduction for a 21-day interval. The HRD score was determined by Myriad myChoice HRD CDx assay with a cutoff of ≥33 for HRD+ and <33 for non-HRD status.

Participants were randomized for disease stage, timing of surgery, residual disease post primary surgery, paclitaxel schedule, geographic region, and germline BRCA status without HRD. The analysis was restricted to patients randomized to carboplatin and paclitaxel with placebo then placebo maintenance (control), and carboplatin and paclitaxel with veliparib, and veliparib maintenance (veliparib-throughout).

Within the BRCAwt population, the participants who were HRD-positive had a PFS hazard ratio (HR) of 0.77 favoring use of veliparib, and the participants who were HRD-negative had a similar PFS HR of 0.76. Comparing HRD score versus observed HR between veliparib-throughout and control revealed that no clear cutoff score could be identified to accurately determine who would benefit most from the veliparib-throughout regimen.

The authors concluded that in patients with BRCAwt carcinomas, HRD score was not predictive of patient outcomes for veliparib-throughout versus control. The use of veliparib-throughout suggests that there may be a benefit from veliparib even at low HRD scores compared with carboplatin and paclitaxel. Additionally, this analysis of BRCAwt HRD-positive and non-HRD populations suggests the veliparib benefit is similar in both groups, according to the study.

Reference

• LBA 6 - 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 Conference website. Published March 28, 2020. https://sgo.confex.com/sgo/2020/meetingapp.cgi/Paper/17045. Accessed April 1, 2020.