Veliparib is an investigational oral poly(ADP-ribose) polymerase inhibitor, or PARP inhibitor, studied primarily with platinum chemotherapy in ovarian cancer, breast cancer, lung cancer, and other solid tumors.
Veliparib is not approved by the US Food and Drug Administration or European Medicines Agency. Its most important Phase 3 programs evaluated veliparib with carboplatin and paclitaxel, followed by maintenance veliparib.
What Is Veliparib?
Veliparib is an oral small-molecule inhibitor of PARP1 and PARP2, enzymes that help cancer cells repair damaged DNA.
PARP inhibition prevents efficient repair of single-strand DNA breaks. During DNA replication, unrepaired damage develops into more serious double-strand breaks. Tumors with deficient homologous recombination repair, including some cancers with BRCA1 or BRCA2 mutations, are particularly vulnerable to this process.
Veliparib has relatively limited PARP-trapping activity compared with some other PARP inhibitors. Its development therefore focused heavily on combining PARP inhibition with DNA-damaging chemotherapy.
Veliparib was previously known as ABT-888.
What Is The Dose Of Veliparib?
There is no approved veliparib dose because the drug remains investigational.
The principal regimen used in the Phase 3 BROCADE3 breast cancer trial was:
Veliparib 120 mg orally twice daily on Days −2 through 5 of each 21-day chemotherapy cycle.
Veliparib was administered with carboplatin and paclitaxel. Patients who discontinued chemotherapy could continue veliparib at 300 mg twice daily, with escalation to 400 mg twice daily when tolerated.
The Phase 3 VELIA ovarian cancer trial used:
- 150 mg orally twice daily continuously during six 21-day cycles of carboplatin and paclitaxel
- Followed by 300 mg twice daily, increasing to 400 mg twice daily when tolerated, during maintenance treatment
These are clinical-trial regimens rather than approved prescribing recommendations.
How Is Veliparib Administered?
Veliparib is taken orally as capsules rather than administered by intravenous infusion or injection.
Depending on the clinical-trial protocol, veliparib was administered either:
- Intermittently around chemotherapy days
- Continuously twice daily
- As maintenance treatment after chemotherapy
Public trial records do not provide one universal instruction regarding administration with food, missed doses, vomiting after administration, or capsule handling. These instructions were determined by each study protocol.
Does Veliparib Require An In-Line Filter?
Veliparib does not require an in-line filter because it is taken orally.
No dilution, infusion bag, intravenous tubing, or line-flushing procedure is required for veliparib itself. Separate preparation and filtration instructions apply to intravenous carboplatin, paclitaxel, or other combination treatments.
Is Premedication Required?
Veliparib does not have a standard drug-specific premedication regimen.
Patients receiving carboplatin and paclitaxel require chemotherapy-related premedications, including antiemetics and agents used to reduce paclitaxel hypersensitivity reactions. Supportive treatment depends on the complete regimen rather than veliparib alone.
Are Dose Reductions Used?
Clinical trials permitted temporary interruption, dose reduction, or permanent discontinuation for toxicity.
Dose modifications were commonly considered for:
- Thrombocytopenia
- Neutropenia
- Anemia
- Nausea or vomiting
- Fatigue
- Persistent gastrointestinal toxicity
- Clinically important nonhematologic adverse effects
In maintenance phases, escalation from 300 mg to 400 mg twice daily occurred only when the lower dose was tolerated.
What Is Known About Veliparib Pharmacokinetics?
Veliparib is orally bioavailable and was developed for twice-daily administration.
Clinical pharmacokinetic studies supported the 120 mg twice-daily intermittent regimen used with carboplatin and paclitaxel in BROCADE3. Higher continuous doses of 300–400 mg twice daily were used when veliparib was administered without concurrent chemotherapy.
Complete approved guidance regarding metabolism, drug interactions, renal impairment, hepatic impairment, and food effects is unavailable because veliparib never received regulatory approval.
Are Renal Or Hepatic Dose Adjustments Required?
No validated renal- or hepatic-impairment dose recommendations have been established.
Clinical studies generally required adequate kidney, liver, and bone-marrow function. Renal function was particularly relevant because patients frequently received platinum chemotherapy, which has its own organ-function requirements and dose-adjustment rules.
What Did Clinical Trials Show?
The Phase 3 VELIA trial evaluated veliparib with first-line carboplatin and paclitaxel, followed by veliparib maintenance, in advanced high-grade serous ovarian cancer.
The veliparib-throughout regimen improved progression-free survival compared with chemotherapy alone, with the largest benefit observed among patients with BRCA-mutated or homologous recombination-deficient tumors. The combination also increased anemia, thrombocytopenia, nausea, and fatigue.
The Phase 3 BROCADE3 trial evaluated veliparib with carboplatin and paclitaxel in HER2-negative advanced breast cancer with germline BRCA1 or BRCA2 mutations.
Watch more: Learn about the Phase 3 BROCADE3 trial evaluating veliparib with carboplatin and paclitaxel in BRCA-mutated advanced breast cancer.
The addition of veliparib significantly improved progression-free survival. However, the final analysis did not establish a clear overall-survival advantage.
Veliparib was also evaluated in lung cancer, glioblastoma, ovarian cancer, and other malignancies, but no study led to regulatory approval.
Watch More: For an expert overview of the Phase 3 BROCADE3 trial, watch: Véronique Diéras, MD – BROCADE3 Phase 3 Trial (ESMO 2019)
What Are The Side Effects Of Veliparib?
Reported adverse effects include:
- Anemia
- Thrombocytopenia
- Neutropenia
- Nausea
- Vomiting
- Fatigue
- Diarrhea
- Reduced appetite
- Headache
Hematologic toxicity became more prominent when veliparib was combined with carboplatin and paclitaxel. In VELIA, anemia and thrombocytopenia occurred more frequently with the veliparib-containing regimen than with chemotherapy alone.
Read more about Paolo Tarantino: Final OS from BROCADE3 phase 3 trial on OncoDaily.
Mirna Antabian, MD
FAQ
Is Veliparib Approved?
No. Veliparib remains investigational and has no FDA- or EMA-approved indication.
Is Veliparib Chemotherapy?
No. Veliparib is an oral targeted PARP1 and PARP2 inhibitor. It was frequently studied with chemotherapy.
How Is Veliparib Taken?
Veliparib is taken orally, usually twice daily. The exact dose and schedule depend on the clinical-trial regimen.
Does Veliparib Require An Infusion Filter?
No. Veliparib is an oral medication and does not require an in-line filter.
What Cancers Was Veliparib Mainly Studied In?
Its largest clinical programs involved advanced ovarian cancer and germline BRCA-mutated, HER2-negative advanced breast cancer.