Safety and efficacy of the oral PARP inhibitor olaparib (AZD2281) in combination with paclitaxel for the first- or second-line treatment of patients with metastatic triple-negative breast cancer: Results from the safety cohort of a phase I/II multicenter trial.

Dent, Rebecca; Lindeman, GJ; Clemons, M; Wildiers, Hans; Chan, Antony C. S.; McCarthy, Nicole; Singer, CF; Lowe, E.S.; Kemsley, Karin; Carmichael, J.

doi:10.1200/jco.2010.28.15_suppl.1018

Cited by 57 publications

(43 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Curiously, the addition of iniparib to chemotherapy did not appear to enhance toxicity and there was no difference in dose reduction rates between the study arms. This is contrary to experience with various other combinations of chemotherapy with other PARP inhibitors where enhanced myelosuppression is invariably seen [35,36]. The explanation for the remarkably positive results seen with iniparib is not clear.…”

Section: How To Optimize the Potential Of Parp Inhibitors?contrasting

confidence: 82%

PARP Inhibitors in BRCA Gene-Mutated Ovarian Cancer and Beyond

Banerjee

Kaye

2011

Curr Oncol Rep

View full text Add to dashboard Cite

Poly(ADP-ribose)polymerase (PARP) inhibitors are showing considerable promise for the treatment of BRCA mutation-associated ovarian and breast cancer. This approach exploits a synthetic lethal strategy to target the specific DNA repair pathway in cancers that harbor mutations in the BRCA1 or BRCA2 genes. Accumulating evidence suggests that PARP inhibitors may have a wider application in the treatment of sporadic, high-grade serous ovarian cancers and other cancers including endometrial cancer. In this review, we discuss the clinical development of PARP inhibitors in ovarian cancer and explore challenges that need to be addressed if the full potential of these agents is to be realized.

show abstract

Section: How To Optimize the Potential Of Parp Inhibitors?contrasting

confidence: 82%

PARP Inhibitors in BRCA Gene-Mutated Ovarian Cancer and Beyond

Banerjee

Kaye

2011

Curr Oncol Rep

View full text Add to dashboard Cite

show abstract

“…Olaparib was well tolerated in combination with weekly paclitaxel in a phase I study in patients with triple-negative breast cancer, however, acceptable dose intensity (ie, missed/delayed doses) was not achieved because of neutropenia, despite secondary prophylaxis with GCSF. Despite the low dose intensity, preliminary analysis of this study demonstrated promising efficacy, with investigator-assessed RECIST response rates of 37% (confirmed partial responses) and 53% (confirmed plus unconfirmed partial responses) [23]. Increased myelotoxicity has been seen in many combination studies with PARP inhibitors, however, another study showed that the combination of gemcitabine/carboplatin with an intravenously administered PARP inhibitor was well tolerated, delivering an improved median overall survival of 12.3 months compared with 7.7 months in the chemotherapy only arm in patients with metastatic triple-negative breast cancer [24].…”

Section: Discussionmentioning

confidence: 92%

Safety and tolerability of the poly(ADP-ribose) polymerase (PARP) inhibitor, olaparib (AZD2281) in combination with topotecan for the treatment of patients with advanced solid tumors: a phase I study

et al. 2011

View full text Add to dashboard Cite

show abstract

“…Results from a phase I/II trial were presented last year. Among the 19 patients advanced breast cancer patients enrolled so far, 37% had investigator confirmed partial responses with the combination of olaparib and paclitaxel, but with higherthan-expected incidence of neutropenia [Dent et al 2010]. On the other hand, a second study using the same compound did not observe any objective responses when administered as single agent in 24 patients with advanced TNBC [Gelmon et al 2010].…”

Section: Dna Repair Pathways: Parp Inhibitorsmentioning

confidence: 99%

Triple-negative breast cancer: are we making headway at least?

et al. 2012

View full text Add to dashboard Cite

Abstract:The so-called triple-negative breast cancer, as defined by tumors that lack estrogen receptor, progesterone receptor and human epidermal growth factor receptor 2 (HER2) overexpression, has generated growing interest in recent years despite representing less than 20% of all breast cancers. These tumors constitute an important clinical challenge, as they do not respond to endocrine treatment and other targeted therapies. As a group they harbor an aggressive clinical phenotype with early development of visceral metastases and a poor long-term prognosis. While chemotherapy remains effective in triple-negative disease, research continues to further identify potential new targets based on phenotypical and molecular characteristics of these tumors. In this respect, the presence of a higher expression of different biomarkers including epidermal growth factor receptor, vascular endothelial growth factor receptor, fibroblast growth factor receptor and Akt activation has led to a proliferation of clinical trials assessing the role of inhibitors to these pathways in triple-negative tumors. Moreover, the described overlap between triple-negative and basal-like tumors, and the similarities with tumors arising in the BRCA1 mutation carriers has offered potential therapeutic avenues for patients with these cancers including poly (ADP-ribose) polymerase inhibitors and a focus on a higher sensitivity to alkylating chemotherapy agents. Results from these trials have shown some benefit in small subgroups of patients, even in single-agent therapy, which reflects the heterogeneity of triple-negative breast cancer and highlights the need for a further subclassification of these types of tumors for better prognosis identification and treatment individualization.

show abstract

Safety and efficacy of the oral PARP inhibitor olaparib (AZD2281) in combination with paclitaxel for the first- or second-line treatment of patients with metastatic triple-negative breast cancer: Results from the safety cohort of a phase I/II multicenter trial.

Cited by 57 publications

References 0 publications

PARP Inhibitors in BRCA Gene-Mutated Ovarian Cancer and Beyond

PARP Inhibitors in BRCA Gene-Mutated Ovarian Cancer and Beyond

Safety and tolerability of the poly(ADP-ribose) polymerase (PARP) inhibitor, olaparib (AZD2281) in combination with topotecan for the treatment of patients with advanced solid tumors: a phase I study

Triple-negative breast cancer: are we making headway at least?

Contact Info

Product

Resources

About