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Olaparib Monotherapy in Patients With Advanced Cancer and a Germline BRCA1/2 Mutation

Open access
Kaufman, Bella, Shapira-Frommer, Ronnie, Schmutzler, Rita K., Audeh, M. William, Friedlander, Michael, Balmaña, Judith, Mitchell, Gillian, Fried, Georgeta, Stemmer, Salomon M., Hubert, Ayala, Rosengarten, Ora, Steiner, Mariana, Loman, Niklas, Bowen, Karin, Fielding, Anitra, Domchek, Susan M.·2015·Journal of Clinical Oncology

Abstract

Purpose: Olaparib is an oral poly (ADP-ribose) polymerase inhibitor with activity in germline BRCA1 and BRCA2 (BRCA1/2) –associated breast and ovarian cancers. We evaluated the efficacy and safety of olaparib in a spectrum of BRCA1/2-associated cancers. Patients and Methods: This multicenter phase II study enrolled individuals with a germline BRCA1/2 mutation and recurrent cancer. Eligibility included ovarian cancer resistant to prior platinum; breast cancer with ≥ three chemotherapy regimens for metastatic disease; pancreatic cancer with prior gemcitabine treatment; or prostate cancer with progression on hormonal and one systemic therapy. Olaparib was administered at 400 mg twice per day. The primary efficacy end point was tumor response rate. Results: A total of 298 patients received treatment and were evaluable. The tumor response rate was 26.2% (78 of 298; 95% CI, 21.3 to 31.6) overall and 31.1% (60 of 193; 95% CI, 24.6 to 38.1), 12.9% (eight of 62; 95% CI, 5.7 to 23.9), 21.7% (five of 23; 95% CI, 7.5 to 43.7), and 50.0% (four of eight; 95% CI, 15.7 to 84.3) in ovarian, breast, pancreatic, and prostate cancers, respectively. Stable disease ≥ 8 weeks was observed in 42% of patients (95% CI, 36.0 to 47.4), including 40% (95% CI, 33.4 to 47.7), 47% (95% CI, 34.0 to 59.9), 35% (95% CI, 16.4 to 57.3), and 25% (95% CI, 3.2 to 65.1) of those with ovarian, breast, pancreatic, or prostate cancer, respectively. The most common adverse events (AEs) were fatigue, nausea, and vomiting. Grade ≥ 3 AEs were reported for 54% of patients; anemia was the most common (17%). Conclusion: Responses to olaparib were observed across different tumor types associated with germline BRCA1/2 mutations. Olaparib warrants further investigation in confirmatory studies.

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Metadata

Authors
Kaufman, B., Shapira-Frommer, R., Schmutzler, R. K., Audeh, M. W., Friedlander, M., Balmaña, J., Mitchell, G., Fried, G., Stemmer, S. M., Hubert, A., Rosengarten, O., Steiner, M., Loman, N., Bowen, K., Fielding, A., & Domchek, S. M.
Venue
Journal of Clinical Oncology
Published
2015-01-20
Volume
33
Issue
3
Pages
244-250
ISSN
  • 0732-183X (ISSN-L)
  • 1527-7755
OpenAlex
W2111437716
Cited by
1,671
References
5
FWCI
68.22
Type
journal article
Language
en
Open access
bronze

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CoChat. (2026). Citation check: Olaparib Monotherapy in Patients With Advanced Cancer and a Germline BRCA1/2 Mutation. https://app.cochat.ai/papers/10.1200/jco.2014.56.2728
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Kaufman, B., Shapira-Frommer, R., Schmutzler, R. K., Audeh, M. W., Friedlander, M., Balmaña, J., Mitchell, G., Fried, G., Stemmer, S. M., Hubert, A., Rosengarten, O., Steiner, M., Loman, N., Bowen, K., Fielding, A., & Domchek, S. M. (2015). Olaparib Monotherapy in Patients With Advanced Cancer and a Germline BRCA1/2 Mutation. Journal of Clinical Oncology. https://doi.org/10.1200/jco.2014.56.2728

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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).

Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.