In the Journals

Olaparib induced tumor response in patients with germline BRCA1/BRCA2 mutations

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December 1, 2014

Olaparib monotherapy induced responses across tumor types in patients with germline BRCA1 or BRCA2 mutations, according to results of a multicenter phase 2 study.

The findings suggest olaparib (Lynparza, AstraZeneca) warrants further investigation in phase 3 trials, the researchers concluded.

Susan M. Domchek, MD, of Abramson Cancer Center at the University of Pennsylvania, and colleagues evaluated 468 adults with advanced solid tumors and known germline BRCA1 or BRCA2 mutations.

Eligible patients had one of the following recurrent cancers: ovarian cancer resistant to prior platinum; breast cancer after three or more chemotherapy regimens for metastatic disease; pancreatic cancer with prior gemcitabine treatment; or prostate cancer that progressed on hormonal and one systemic therapy.

All patients received 400 mg twice-daily olaparib, an oral PARP inhibitor that has demonstrated activity in BRCA-associated breast and ovarian cancers. Treatment continued until cancer progression. If toxicities developed, doses were decreased to 200 mg or 100 mg as needed.

Tumor response rate served as the primary endpoint. Secondary endpoints included objective response rate, PFS and response duration.

The analysis included 298 evaluable patients. Researchers reported an overall tumor response rate of 26.2% (95% CI, 21.3-31.6). They reported the following response rates based on tumor type: prostate cancer, 50% (95% CI, 15.7-84.3); ovarian cancer, 31.1% (95% CI, 24.6-38.1); pancreatic cancer, 21.7% (95% CI, 7.5-43.7); and breast cancer, 12.9% (95% CI, 5.7-23.9).

Overall, 42% (95% CI, 36-47.4) demonstrated stable disease at 8 weeks or beyond. Rates by tumor type were 47% for patients with breast cancer, 40% for those with ovarian cancer, 35% for patients with pancreatic cancer and 25% for those with prostate cancer.

The most common adverse events were fatigue, nausea and vomiting. About half of patients (54%) experienced grade ≥3 adverse events, the most common of which was anemia (17%).

Disclosure: The researchers report research funding from, employment or leadership positions with, consultant or advisory roles with, honoraria from or stock ownership in AbbVie, AstraZeneca and Clovis Oncology.

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