Veliparib Improves PFS in BRCA Wild-Type Ovarian Cancer, Regardless of HRD Status

Elizabeth Swisher, MD

Veliparib (ABT-888) plus chemotherapy extended progression-free survival (PFS) for BRCA wild-type patients with high-grade serous carcinoma (HGSC), according to new findings from the phase III VELIA/GOG-3005 trial. Lead author Elizabeth M. Swisher, MD, said that patients derived benefit irrespective of homologous recombination deficiency (HRD) status.

Swisher, director of Division of Gynecologic Oncology at the University of Washington and coleader of Breast and Ovarian Cancer Research Program at the Seattle Cancer Care Alliance, was scheduled to present this new data during the 2020 SGO Annual Meeting.

The hazard ratios for PFS were nearly identical between the non-HRD and HRD groups and both groups derived a PFS benefit of approximately 3 months, Fisher noted. These results may mean HRD status is prognostic for outcome, but not predictive for response to veliparib.¹

“What is different between the 2 groups is the absolute PFS, which suggests that HRD is a prognostic factor,” she said in an interview with OncLive^®. “It didn’t predict response to the PARP inhibitor, but it did predict overall a better outcome regardless of whether the patient got the PARP inhibitor.”

In this analysis, patients were assigned to a control arm of carboplatin and paclitaxel with placebo followed by placebo as maintenance (n = 375) or 150 mg twice-daily veliparib plus chemotherapy followed by 400 mg twice-daily veliparib monotherapy as maintenance therapy (n = 382).

VELIA included a third arm in which patients received veliparib plus chemotherapy followed by placebo maintenance (n = 383), but analysis of that patient population was not included in these data.

Investigators evaluated PFS in BRCA wild-type patients by Myriad myChoice Genomic Instability Score (GIS) to determine the relative predictive value of this component of the HRD assay. The prespecified GIS cutoff was 33, rather than the traditional 42.

For patients with HRD HGSC (n = 227), the median PFS was 23.5 months versus 20.2 months in favor of the veliparib arm compared with placebo (HR, 0.77; 95% CI, 0.54-1.10). Investigators observed 128 PFS events during the study period.

For patients with non-HRD HGSC (n = 255), the median PFS was 15.4 months in the experimental group versus 12.3 months with placebo (HR, 0.76; 95% CI, 0.55-1.03). Investigators observed 171 PFS events.

Swisher said the GIS cutoff did not play a role in the PFS results—the benefit was the same at 33 and 42. “There’s not a better inflection point,” she added.

Looking at results from the phase III PAOLA-1 trial of olaparib (Lynparza) plus bevacizumab (Avastin) for women with newly-diagnosed advanced ovarian cancer who had a complete or partial response to first-line treatment with platinum-based chemotherapy and bevacizumab, Swisher said non-HRD may be a negative predictor for some patients in some settings. Among patients treated with olaparib, the median PFS for patients with HRD HGSC was 37.2 months compared with 16.9 months for patients with non-HRD cancers.²

“In PAOLA-1, [HRD status] was quite predictive, but maybe not as a way to predict who responds but [instead] to say there’s no point to adding PARP inhibitor in the setting of bevacizumab for non-HRD cases,” she said. “How a biomarker behaves has to do with the patient population, potentially, but also the treatment setting.”

Improved PFS in Frontline

In data previously presented at the 2019 European Society for Medical Oncology Congress and simultaneously published in the New England Journal of Medicine, the median PFS among all patients with HRD HGSC was 31.9 months in those receiving veliparib throughout the VELIA/GOG-3005 trial compared with 20.5 months in the control arm (HR, 0.57; 95% CI, 0.43-0.76; P <.001).^3,4

The median PFS in the combined induction and maintenance phases was 23.5 months in the veliparib arms compared with 17.3 months in the placebo arm (HR, 0.68; 95% CI, 0.56-0.83; P <.001).

The benefit was more pronounced for those with BRCA mutations. In this group, the median PFS was 34.7 months compared with 22.0 months for veliparib and placebo, respectively (HR, 0.44; 95% CI, 0.28-0.68; P <.001).

In those receiving veliparib with induction chemotherapy followed by placebo maintenance, the median PFS across the full study was 15.2 months compared with 17.3 months in the control arm (HR, 1.07; 95% CI, 0.90-1.29). In the BRCA group, the median PFS was 21.1 months with this regimen compared with 22.0 months for the control (HR, 1.22; 95% CI, 0.82-1.80). In the HRD group, the median PFS was 18.1 months with the combination compared with 20.5 months for the control (HR, 1.10; 95% CI, 0.86-1.41).

References

1. Swisher EM, Kaufmann SH, Birrer MJ, et al. Exploring the relationship between homologous recombination score and progression free survival in BRCA wildtype ovarian carcinoma: Analysis of veliparib plus carboplatin/paclitaxel in the phase 3 VELIA/GOG 3005 study. Data made available as part of the virtual platform for the SGO 2020 Annual Meeting.
2. Ray-Coquard I, Pautier P, Pignata S, et al. Olaparib plus bevacizumab as first-line maintenance in ovarian cancer. N Engl J Med. 2019;381(25):2416-2428. doi: 10.1056/NEJMoa1911361.
3. Coleman RL, Fleming GF, Brady MF, et al. VELIA/GOG-3005: Integration of veliparib (V) with front-line chemotherapy and maintenance in women with high-grade serous carcinoma of ovarian, fallopian tube, or primary peritoneal origin (HGSC). Presented at: ESMO Congress 2019, Barcelona, Spain, September 27 to October 1, 2019. LBA3.
4. Coleman RL, Fleming GF, Brady MF, et al. Veliparib with first-line chemotherapy and as maintenance therapy in ovarian cancer. N Engl J Med. 2019; 381:2403-2415. doi: 10.1056/NEJMoa1909707.