Study: New PARP inhibitor veliparib showed benefit as first-line treatment for ovarian cancer

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At a glance Clinical trials
What is first-line treatment?  Guidelines              
What is maintenance therapy? Questions for your doctor 
What does this mean for me? Resources and reference


This study is about: 

Whether veliparib slows down progression of advanced ovarian cancer when used during chemotherapy and continued alone afterwards as a maintenance therapy.

Why is this study important? 

Veliparib is a type of medication known as a PARP inhibitor. Some PARP inhibitors have been approved for treatment of a variety of cancers. This study asks if veliparib can delay tumor progression when given with chemotherapy and then continued as a maintenance therapy for women with untreated, advanced-stage ovarian cancer. Veliparib is a new PARP inhibitor that has not yet received FDA approval to treat ovarian cancer.

To date, no PARP inhibitors have been approved to be used in combination with chemotherapy. This study is novel in that it was the first completed phase III trial that looked at combined use of a PARP inhibitor with primary chemotherapy. (Phase III trials are the last phase of drug testing that can determine if a drug will be approved.) This and other studies may lead to approval of PARP inhibitors as frontline therapies for some women with advanced ovarian cancer.

Study findings:

Researchers showed that cancer progressed more slowly in women who were treated with veliparib during and after chemotherapy compared with women treated with chemotherapy alone.

  • Participants who took veliparib went 6 months longer before their cancer returned or worsened, compared with those treated with chemotherapy alone.
  • Participants with an inherited or tumor mutation in BRCA1 or BRCA2 who took veliparib had almost 13 additional months before cancer returned or worsened, compared with women who were treated with chemotherapy alone.
  • Among participants whose tumor had a feature called HRD-positive (homologous recombination deficiency), those who took veliparib had an additional 11½  months before cancer returned or worsened, compared with those who had chemotherapy alone.

Compared with the chemotherapy alone group, participants in the veliparib group had a higher incidence of:

  • tiredness
  • nausea and vomiting
  • low red blood cell count (anemia)
  • low white blood cell count (leukopenia)\
  • low platelet count (thrombocytopenia)

What is first-line treatment?

First-line treatment is the initial treatment given for a disease, such as cancer. Second-line treatments are used for cancers that return or do not respond to treatment. 

For most women diagnosed with ovarian cancer, first-line treatment usually involves surgery and several months of chemotherapy. Women whose cancer responds well may stop treatment altogether or stop treatment and start maintenance therapy

Women whose cancer comes back receive second-line treatment, which may be a new course of chemotherapy or another type of treatment. Third-line treatment is recommended for cancers that return or do not respond to treatment.


What is maintenance therapy?

Maintenance therapy is given after chemotherapy to try to keep the cancer from returning. The goal is to extend the length of time before recurrence or to turn remission into a long-term cure.

What does this mean for me? 

Currently, veliparib has not received FDA approval for ovarian cancer.  However, it is a part of the PARP inhibitor drug class. Three PARP inhibitors have received FDA approval as a maintenance therapy in individuals with ovarian cancer who have had a partial response to chemotherapy as an initial treatment:

  • Lynparza (olaparib)
  • Rubraca (rucaparib)
  • Zejula (niraparib)

If you have advanced ovarian cancer, you may want to ask your healthcare provider about PARP inhibitor options for your treatment. Because people with inherited mutations in BRCA respond better to PARP inhibitors in general, you may want to consider genetic testing if you have not already had it done. If you know that you have an inherited BRCA mutation or other cancer gene mutation, it is important to inform your healthcare provider, as it may change their treatment recommendations.

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This article is relevant for:

Women with advanced-stage ovarian cancer

This article is also relevant for:

Metastatic cancer

Ovarian cancer survivors

People with a genetic mutation linked to cancer risk

Women under 45

Women over 45

Platinum sensitive ovarian cancer

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Questions to Ask Your Doctor

  • What are the best treatments for my ovarian cancer given my personal and family history?
  • Should I consider having genetic testing for inherited cancer mutations?
  • What are my options for maintenance therapy after chemotherapy?
  • What type of side effects should I expect from a PARP inhibitor?
  • Do I qualify for any clinical trials?

Open Clinical Trials

Who covered this study?


PARP inhibitors take big step toward changing practice This article rates 4.0 out of 5 stars

Kaiser Permanente

A promising treatment for ovarian cancer This article rates 3.0 out of 5 stars


Frontline veliparib shows intriguing PFS findings in VELIA trial This article rates 2.0 out of 5 stars

How we rated the media


Study background: 

Veliparib is an investigational drug that belongs to the drug class of PARP inhibitors that can be taken orally. In early-phase clinical trials, veliparib was shown to hinder tumor progression when administered alone or combined with initial treatment with chemotherapy in patients with advanced ovarian cancer (with or without BRCA mutations).

Veliparib has not yet received FDA approval for ovarian cancer. Three PARP inhibitors (olaparib, niraparib and rucaparib) have been approved as a maintenance therapy for ovarian cancer in patients who have had a complete or partial response to platinum chemotherapy. However, research is limited showing the safety and effectiveness of PARP inhibitors when they are taken during chemotherapy and continued after chemotherapy in a maintenance role.

Researchers of this study wanted to know:  

Whether veliparib is safe and effective in delaying cancer progression when administered with initial chemotherapy and continued as a maintenance monotherapy in women with newly diagnosed stage III and IV ovarian cancers (including fallopian and peritoneal cancers).

Populations looked at in this study: 

The study included 1,140 women age 18 and older with newly diagnosed and untreated stage III and IV ovarian cancer.

Blood samples were taken from all patients to test for an inherited BRCA mutation. In addition, a tumor sample from each participant was tested to see if it had an acquired BRCA mutation or a feature called homologous-recombinant deficiency (HRD-positive)—a deficiency characterized by the inability to repair breaks in DNA. A total of 298 patients (26 percent of participants) had an inherited mutation or tumor mutation in BRCA (identified as the BRCA group). The HRD-positive group consisted of 627 patients (55 percent of participants). The HRD-positive group included the patients whose tumors had a BRCA mutation and patients whose tumor had HRD.

Study design:                    

The phase III trial was conducted at 202 sites in 10 countries from July 2015 to July 2017.  

Patients were randomized in a 1:1:1 ratio to one of the following treatment groups:

  1. Placebo group (375 patients): Received placebo and chemotherapy, followed by maintenance therapy with placebo only.
  2. Veliparib-combination group (383 patients): Received veliparib and chemotherapy, followed by maintenance therapy with placebo only.
  3. Veliparib-throughout group (382 patients): Received veliparib and chemotherapy, followed by maintenance therapy with veliparib only.

Each treatment group went through six cycles of chemotherapy (carboplatin and paclitaxel) followed by 30 cycles of maintenance therapy. All cycles throughout the study lasted 21 days each. During chemotherapy, veliparib or placebo was given as a tablet of 150 mgs twice daily, and from 300 to 400 milligrams twice daily during maintenance therapy. Carboplatin and paclitaxel (chemotherapy) were administered once every 21 days.

The primary endpoint was progression-free survival—the amount of time it takes for cancer to return or worsen after treatment.

  • Primary endpoint was compared between the veliparib-throughout group and the placebo group).

The secondary endpoints included:

  1. the progression-free survival in the veliparib-combination group versus the veliparib-throughout group
  2. overall survival of all study participants

Study findings:   

All patients randomized to the veliparib-throughout group had a median progression-free survival of 23.5 months as compared with 17.5 months for patients in the placebo throughout group. 

  • Within the BRCA group (patients with an inherited BRCA mutation or whose tumor has a BRCA mutation), those taking veliparib throughout had a median progression-free survival of 34.7 months as compared with 22 months in those taking placebo throughout.
  • Within the HRD-positive group (patients whose tumors had BRCA mutations or HRD, which includes the BRCA group above), median progression-free survival of patients taking veliparib throughout was 31.9 months compared with 20.5 months for those taking placebo throughout.

There was no significant difference in median progression-free survival among patients who received veliparib-combined treatment versus those who received either veliparib-throughout or placebo-throughout.  More studies are needed to determine the benefits of veliparib-combined treatment with chemotherapy only in women with newly diagnosed advanced ovarian cancer.

Researchers reported that overall survival among patients could not be determined yet.

The most common side effects attributed by any treatment with veliparib included:

  • tiredness
  • nausea
  • low red blood cell counts (anemia)
  • low white blood cell counts (leukopenia)
  • low platelet counts (thrombocytopenia)

The veliparib-throughout group, compared with the other treatment groups, was most likely to discontinue the trial due to adverse events unrelated to tumor progression. Discontinuation rates for this reason per group were 22 percent for veliparib-throughout, 9 percent for veliparib-only, and 3 percent for the control groups respectively.

Strengths and Limitations:

A major strength of the study was that it showed veliparib-throughout treatment to be effective in patients with a BRCA mutation, and also in patients without a BRCA mutation. This is important because PARP inhibitors are often referred or studied in the context of benefiting patients with BRCA-related cancer.

As for limitations, the researchers highlighted that the trial design did not include a “veliparib maintenance-only” group and therefore did not address the sole contribution of veliparib as a maintenance therapy in extending progression-free survival. This makes it challenging to determine how veliparib maintenance therapy may compare with other PARP inhibitors already approved for ovarian cancer treatment.

Limitations that were not mentioned by the researchers included:

  • Lack of diversity across race/ethnicity—racial categories for patients included only “White,” “Asian” and “other.”
  • Absence of data concerning veliparib’s impact in patients with other inherited mutations that may contribute to HRD-positive status.
  • Lack of data pertaining to overall survival of patients after they completed treatment.
  • There is no comparison to other PARP inhibitors, so it is unknown which drug is most effective in this setting.


This current study adds to previous trials with veliparib which showed the drug to be safe when used as a monotherapy or combined with chemotherapy in patients with advanced-stage ovarian cancer with or without a BRCA mutation.

Veliparib is currently in phase III trials as treatment for ovarian, breast and lung cancers. The FDA granted orphan drug status to veliparib for the treatment of advanced squamous non–small cell lung cancer.


A combined regimen of chemotherapy (carboplatin and paclitaxel) and veliparib, followed by veliparib maintenance therapy led to significantly longer progression-free survival than chemotherapy alone in patients with advanced ovarian cancer—regardless of HRD or BRCA mutation status. Patients with BRCA tumor mutations responded better than those without BRCA tumor mutations.

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Posted 8/18/20 

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