Adding Veliparib Extended Time Without Disease Progression in Metastatic Ovarian Cancer, Phase 3 Trial Finds

Using veliparib in combination with chemotherapy as first-line and then maintenance therapy post-surgery significantly extended the time without disease progression in women with newly diagnosed metastatic high-grade serous (HGS) ovarian cancer, according to Phase 3 trial results.

The research was presented in the session, “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,” at the 2019 European Society for Medical Oncology (ESMO) Congress and published in the New England Journal of Medicine.

Veliparib is an investigational PARP enzyme inhibitor developed by AbbVie. It is designed to prevent cancer cells from repairing DNA errors and thereby cause their death.

The international, AbbVie-sponsored VELIA Phase 3 trial (NCT02470585) assessed the potential benefits of adding veliparib to standard chemotherapy with carboplatin and Taxol (paclitaxel) — and as maintenance therapy — for patients with stage III or IV HGS epithelial ovarian, fallopian tube, or primary peritoneal cancer.

“This is the first clinical trial to use a PARP inhibitor combined with chemotherapy for newly diagnosed ovarian cancer patients,” Robert L. Coleman, MD, the study’s lead investigator and a professor at The University of Texas MD Anderson Cancer Center, said in a news release.

“The patient population enrolled in the trial were reflective of those we see in clinic every day as it allowed for both stage III and stage IV patients and those getting primary surgery or those undergoing neoadjuvant chemotherapy before surgery,” he added.

From July 2015 and July 2017, a total of 1,140 participants were randomly assigned to this treatment regimen; to chemotherapy and a placebo followed by placebo maintenance (control group); or to chemotherapy and veliparib followed by placebo (veliparib combination only). The median age was 62 years across the three groups.

While chemotherapy was given over six cycles with a 21-day interval, veliparib was given orally twice per day at 150 mg during chemotherapy and at 400 mg over 30 cycles during maintenance.

Among VELIA’s participants, 55% had homologous recombination (HR) deficiency, which refers to a faulty DNA repair pathway characterized by exchanged DNA sequences between two similar or identical molecules. About 26% had BRCA mutations, which also affect DNA repair.

The median follow-up duration was 28 months. Among patients with BRCA mutations, the combination approach followed by maintenance with veliparib led to a longer median period (34.7 months) without disease worsening — or progression-free survival (PFS) — than the control treatment (22 months). The veliparib combination and maintenance also led to longer PFS in patients with any HR deficiency — 31.9 months vs. 20.5 months in the control group.

Patients on the combination and maintenance therapy achieved a PFS of 23.5 months, compared with 17.3 months in the controls.

For patients receiving the veliparib combination and placebo maintenance, the PFS was 21.1 months for those with BRCA mutations, 18.1 months for those with HR deficiency, and 15.2 months for the overall population, which were not significantly different from the control group.

Using veliparib with chemotherapy was well-tolerated, although this group showed a higher incidence of anemia and lower platelet count, and veliparib was generally associated with nausea and fatigue. During maintenance, less than 8% of the patients on veliparib had a serious or life-threatening adverse event. Overall, the side effects associated with veliparib were consistent with its safety profile, the team noted.

“These results further validate the role of this class of drug in the treatment of patients with ovarian cancer and offer a new therapeutic asset that can be initiated with the start of their adjuvant chemotherapy treatment,” Coleman said, while adding that the observed benefits apply to most patients with newly diagnosed ovarian cancer.

The team plans to test combinations of veliparib with other types of treatments, including immunotherapy and anti-angiogenic agents such as Avastin (bevacizumab, by Genentech), mainly during the maintenance phase.

Of note, several of the study’s authors received funding or were consultants/members of advisory boards for AbbVie. Three are employees and stockholders of the company.