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Veliparib is a PARP inhibitor that AbbVie tested with chemotherapy in breast cancer. It added nothing to carboplatin before surgery (BrighTNess) and lengthened progression-free but not overall survival with carboplatin and paclitaxel in inherited BRCA advanced disease (BROCADE3), so it was never licensed.
Veliparib inhibits the catalytic activity of PARP1 and PARP2 but traps PARP on DNA far less than olaparib or talazoparib, which is why it could be combined with full-dose chemotherapy where the other PARP inhibitors cannot. That property was tested in two phase 3 breast cancer trials. In BrighTNess (634 patients, stage II to III triple-negative disease) paclitaxel with carboplatin and veliparib gave a pathological complete response in 53 percent against 58 percent with paclitaxel and carboplatin and 31 percent with paclitaxel alone, so the gain came from carboplatin; at 4.5 years the event-free survival hazard ratio for the veliparib arm against carboplatin alone was 1.12. In BROCADE3 (509 patients with a germline BRCA1 or BRCA2 mutation and HER2-negative advanced breast cancer, up to two prior chemotherapy lines) adding veliparib to carboplatin and paclitaxel improved median progression-free survival from 12.6 to 14.5 months (hazard ratio 0.71, p 0.0016) but final overall survival was 32.4 versus 28.2 months (hazard ratio 0.92, p 0.43), with grade 3 or worse neutropenia in 81 versus 84 percent and thrombocytopenia in 40 versus 28 percent. AbbVie did not file for approval in breast cancer; veliparib remains an investigational agent and the two trials are the reference for why weak PARP trapping with chemotherapy did not translate into survival.
Catalytic inhibition of PARP1 and PARP2 with minimal PARP-DNA trapping; sensitises to platinum and alkylating chemotherapy. Connects to PARP and BRCA1 / BRCA2 (HRD).
1.Veliparib slips into a pocket on PARP.
Background: ADC sequencing, Antigen escape (antigen loss, lineage switch), BCG-unresponsive, Castration-resistant prostate cancer (CRPC), Circulating tumour DNA (ctDNA). Also on OnCo: Resistance atlas · Lines of therapy.
| Adverse event | Any grade | Grade 3+ |
|---|---|---|
| Neutropenia (grade 3 or worse), with carboplatin and paclitaxel BROCADE3 veliparib arm; 84 percent in the placebo arm | - | 81% |
| Thrombocytopenia (grade 3 or worse) BROCADE3 veliparib arm; 28 percent with placebo | - | 40% |
Rates read from the source. Blank cells mean the figure was not sourced, not that it is zero.
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Query for this drug: (TITLE:"Veliparib" OR ABSTRACT:"Veliparib" OR TITLE:"ABT-888" OR ABSTRACT:"ABT-888") AND (cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma). Results are unfiltered search hits about Veliparib, not a curated reading list.
Shares PARP, PARP inhibitors, BRCA1 / BRCA2 (HRD), Triple-negative breast cancer (TNBC).
Shares BROCADE3, PARP, PARP inhibitors, BRCA1 / BRCA2 (HRD).
Shares PARP inhibitors, BRCA1 / BRCA2 (HRD), Triple-negative breast cancer (TNBC), HR-positive / HER2-negative breast cancer.
Shares BROCADE3, PARP, PARP inhibitors, BRCA1 / BRCA2 (HRD).
Shares PARP, PARP inhibitors, BRCA1 / BRCA2 (HRD), Triple-negative breast cancer (TNBC).
Shares PARP, BRCA1 / BRCA2 (HRD), Triple-negative breast cancer (TNBC), HR-positive / HER2-negative breast cancer.
Shares BrighTNess, PARP inhibitors, BRCA1 / BRCA2 (HRD), Early triple-negative breast cancer.
Shares PARP, PARP inhibitors, BRCA1 / BRCA2 (HRD).