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Clinical Trial
. 2015 Jan 20;33(3):244-50.
doi: 10.1200/JCO.2014.56.2728. Epub 2014 Nov 3.

Olaparib monotherapy in patients with advanced cancer and a germline BRCA1/2 mutation

Bella Kaufman  1 , Ronnie Shapira-Frommer  1 , Rita K Schmutzler  1 , M William Audeh  1 , Michael Friedlander  1 , Judith Balmaña  1 , Gillian Mitchell  1 , Georgeta Fried  1 , Salomon M Stemmer  1 , Ayala Hubert  1 , Ora Rosengarten  1 , Mariana Steiner  1 , Niklas Loman  1 , Karin Bowen  1 , Anitra Fielding  1 , Susan M Domchek  2
Affiliations
Clinical Trial

Olaparib monotherapy in patients with advanced cancer and a germline BRCA1/2 mutation

Bella Kaufman et al. J Clin Oncol. .

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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Conflict of interest statement

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

Figures

Fig 1.
Fig 1.
Progression-free survival.
Fig 2.
Fig 2.
Overall survival.
See this image and copyright information in PMC

Comment in

References

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