A phase I study of veliparib (ABT-888) in combination with weekly carboplatin and paclitaxel in advanced solid malignancies and enriched for triple-negative breast cancer (TNBC).

Pahuja, Shalu; Beumer, Jan H.; Appleman, Leonard Joseph; Tawbi, Hussein Abdul-Hassan; Stoller, Ronald G.; Lee, James J.; Lin, Yan; Ding, Fei; Yu, Jing; Belani, Chandra P.; Chen, Alice; Giranda, Vincent L.; Shepherd, Stacie Peacock; Chu, Edward; Puhalla, Shannon

doi:10.1200/jco.2015.33.15_suppl.1015

Cited by 26 publications

(17 citation statements)

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“…Several early phase studies with the other PARPis demonstrated similar signals of efficacy in BRCAmutant breast cancer ( Table 2). [29][30][31][32][33][34][35][36][37][38][39][40][41][42][43][44][45][46][47] Multiple phase 2 studies further demonstrated activity of olaparib in patients who had metastatic breast cancer with germline BRCA mutations. [30][31][32] In a phase 2 study, Tutt et al investigated the effects of olaparib monotherapy in 54 patients who had centrally confirmed, germline BRCA-mutant breast cancer.…”

Section: Single-agent Parpis In Metastatic Breast Cancermentioning

confidence: 99%

“…In a dose escalation study of veliparib plus carboplatin and paclitaxel in patients with advanced solid tumors, promising activity was observed, with an ORR of 57% in the breast cancer cohort. Additional phase 1 data from patients with breast cancer established the recommended phase 2 dose of veliparib as 150 mg twice daily (on days −2 to +5) with carboplatin (area under the curve 2) and paclitaxel (80 mg/m 2 ) on days 1, 8, and 15 . Because of myelosuppression, this dose is lower than the single agent maximum tolerated dose.…”

Section: Clinical Development In Breast Cancermentioning

confidence: 99%

“…21,22 Given these preclinical data, several clinical trials are studying combination therapy with the goal of potentiating the effect of cytotoxic chemotherapy (Table 2). 34,35,[42][43][44][45][46][47]51 In particular, veliparib has been explored as part of combination therapy. In a dose escalation study of veliparib plus carboplatin and paclitaxel in patients with advanced solid tumors, promising activity was observed, with an ORR of 57% in the breast cancer cohort.…”

Section: Parpis In Combination With Chemotherapy In Metastatic Breastmentioning

confidence: 99%

“…Additional phase 1 data from patients with breast cancer established the recommended phase 2 dose of veliparib as 150 mg twice daily (on days 22 to 15) with carboplatin (area under the curve 2) and paclitaxel (80 mg/m 2 ) on days 1, 8, and 15. 46 Because of myelosuppression, this dose is lower than the single agent maximum tolerated dose. The subsequent randomized phase 2 BROCADE trial studied the combination of veliparib and temozolomide or carboplatin/paclitaxel in patients with platinum-naive, BRCA-mutant, metastatic breast cancer.…”

Section: Parpis In Combination With Chemotherapy In Metastatic Breastmentioning

confidence: 99%

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PARP inhibitors in breast cancer: Bringing synthetic lethality to the bedside

Turk

Wisinski

2018

Cancer

117

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Individuals with breast and ovarian cancer susceptibility gene 1 (BRCA1) or BRCA2 germline mutations have a significantly increased lifetime risk for breast and ovarian cancers. BRCA-mutant cancer cells have abnormal homologous recombination (HR) repair of DNA. In these tumors, the base excision repair (BER) pathway is important for cell survival. The poly(adenosine diphosphate-ribose) polymerase (PARP) enzymes play a key role in BER, and PARP inhibitors are effective in causing cell death in BRCA-mutant cells while sparing normal cells-a concept called synthetic lethality. PARP inhibitors are the first cancer therapeutics designed to exploit synthetic lethality. Recent clinical trials in BRCA-mutant, metastatic breast cancer demonstrated improved outcomes with single-agent PARP inhibitors (olaparib and talazoparib) over chemotherapy. However, resistance to PARP inhibitors remains a challenge. Primarily due to myelosuppression, the combination of PARP inhibitors with chemotherapy has been difficult. Novel combinations with chemotherapy, immunotherapy, and other targeted therapies are being pursued. In this review, the authors discuss current knowledge of PARP inhibitors in BRCA-mutant breast cancer and potential future directions for these agents. Cancer 2018;124:2498-506. © 2018 American Cancer Society.

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Section: Single-agent Parpis In Metastatic Breast Cancermentioning

confidence: 99%

Section: Clinical Development In Breast Cancermentioning

confidence: 99%

Section: Parpis In Combination With Chemotherapy In Metastatic Breastmentioning

confidence: 99%

Section: Parpis In Combination With Chemotherapy In Metastatic Breastmentioning

confidence: 99%

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PARP inhibitors in breast cancer: Bringing synthetic lethality to the bedside

Turk

Wisinski

2018

Cancer

117

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“…However, various encouraging, and effective, veliparib combination trials have been presented or reported in 2015. Promising preliminary results have been reported in combination with irinotecan (27) and along with carboplatin/paclitaxel (28) in patients with triple negative breast cancer (TNBC). Preliminary phase I results of veliparib in combination with intravenous and intraperitoneal paclitaxel/cisplatin +/- bevacizumab in the adjuvant setting have achieved safe recommended phase II dose of Veliparib at 150mg BID (29).…”

Section: Introductionmentioning

confidence: 99%

Delivering on the promise

Coyne

Chen

Kummar

2015

Current Opinion in Oncology

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Purpose of the review Authors present the rationale, clinical development, and current status of Poly (adenosine diphospohate [ADP]) ribose polymerase (PARP) inhibitors (PARPi) as anticancer agents. Recent Findings The recent approval of olaparib in heavily pre-treated patients with advanced ovarian cancer carrying a BRCA1/2 mutation represents a significant therapeutic advance for patients with this difficult to treat disease. Though olaparib is the first agent in this class to be approved, multiple PARPis are in various stages of clinical development, including in combination with other treatment modalities such as radiation, anti-angiogenic agents, and cytotoxic chemotherapies. Summary Clinical benefit has been observed with PARPis in patients with advanced BRCA1/2 mutant ovarian and breast cancers. Various PARPis, either as single agents or in combination, are being evaluated in the neoadjuvant, adjuvant and metastatic settings.

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