In a recent phase 3 trial, Lynparza improved progression-free survival in patients with BRCA-positive, HER2-negative breast cancer.
Progression-free survival (PFS) was improved with Lynparza (olaparib) versys standard chemotherapy for patients with BRCA-positive, HER2-negative breast cancer, according to the findings from OLYMPIAD, a phase 3 trial announced by AstraZeneca, the manufacturer of the PARP inhibitor.
The company is continuing to evaluate the study data and plans to present the full results at an upcoming medical meeting, as well as communicate with regulatory authorities regarding the results. The initial safety data are consistent with previous Lynparza studies, according to AstraZeneca.
“These results are positive news for patients with BRCA-mutated metastatic breast cancer, a disease with a high unmet need, and are the first positive phase 3 data for a PARP inhibitor beyond ovarian cancer. This is highly encouraging for the development of our broad portfolio which aims to treat multiple cancers by targeting DNA damage response pathways,” Sean Bohen, M.D., Ph.D., executive vice president, Global Medicines Development, and chief medical officer at AstraZeneca, said in a statement.
The phase 3 multicenter OLYMPIAD trial included 302 patients with HER2-negative metastatic breast cancer who harbored germline BRCA1 or BRCA2 mutations. The study was conducted in 19 countries across Europe, Asia, North America and South America.
Patients were randomized to Lynparza (300 mg twice daily) or physician’s choice of standard chemotherapy (capecitabine, vinorelbine or eribulin). The primary endpoint of the trial was PFS per a blinded independent review. Secondary endpoints included overall survival, time to second progression or death, objective response rate (ORR) and effect on health-related quality of life.
Positive results for Lynparza in this setting were previously shown in a phase 2 proof-of-concept trial (NCT00494234) published in the The Lancet in 2010. The study was conducted at 16 centers in Australia, Germany, Spain, Sweden, the United Kingdom and the United States.
The study assigned women with recurrent, advanced breast cancer and BRCA1 or BRCA2 mutations to two sequential cohorts. The first cohort (27 patients) received continuous oral Lynparza at the maximum-tolerated dose (400 mg twice daily) and the second cohort (27 patients) received 100 mg twice daily.
The median number of prior chemotherapy regimens was three (range, 1-5 in cohort 1, and 2-4 in cohort 2). The primary efficacy endpoint was ORR. Among patients in the 400-mg cohort, the ORR was 41 percent, and the ORR was 22 percent for the 100-mg cohort.
Most of the reported adverse events (AEs) were low grade. In the 400-mg cohort, the most common AEs included fatigue (grade 1/2, 11 patients [41 percent]; grade 3 or 4, four patients [15 percent]), nausea (grade 1/2, 11 patients [41 percent]; grade 3/4, four patients [15 percent]), vomiting (grade 1/2, three patients [11 percent]; grade 3/4, three patients [11 percent]), and anemia (grade 1/2, one patients [4 percent]; grade 3/4, three patients [11 percent]).
In the 100-mg short, the most common AEs were nausea (grade 1/2, 11 patients [41 percent]; no grade 3/4) and fatigue (grade 1/2, seven patients [26 percent]; grade 3/4, one patient [4 percent]).
BRCA testing in the OLYMPIAD trial was done using Myriad Genetics BRACAnalysis CDx test. The test detected positive germline BRCA1/2 mutations in 98 percent (297/302) of the patients enrolled in the trial.
"We believe the results of the OLYMPIAD trial support use of the BRACAnalysis CDx test to help inform treatment decisions in the metastatic breast cancer setting and will expand the patient population who can benefit from BRCA testing," Johnathan Lancaster, M.D., Ph.D., chief medical officer of Myriad Genetic Laboratories, said in a statement. "This study underscores Myriad's commitment to our pharmaceutical partners and to advancing the field of personalized medicine so that new, effective treatment options are available to patients."
The FDA approved Lynparza in December 2014 for the treatment of women with BRCA-positive advanced ovarian cancer following treatment with three or more prior lines of chemotherapy. The BRACAnalysis CDx test was simultaneously approved as a companion diagnostic.