FDA News

FDA approves Lynparza, first treatment for BRCA-mutated breast cancer

The FDA expanded the indication of olaparib to include patients with germline BRCA-mutated, HER-2-negative metastatic breast cancer who were previously treated with chemotherapy.

Olaparib (Lynparza; AstraZeneca, Merck) — a poly ADP-ribose polymerase inhibitor — is indicated for the treatment of patients with BRCA-mutated, advanced ovarian cancer who have received three or more chemotherapy treatments and for the maintenance treatment of patients with recurrent epithelial ovarian, fallopian tube or primary peritoneal cancer whose tumors have completely or partially responded to chemotherapy.

Patients are selected for olaparib therapy based on the BRCAnalysis CDx (Myriad Genetic Laboratories) gene test, which also received expanded indication from the FDA to include detection of BRCA mutations in blood samples from patients with breast cancer.

The FDA based these expanded indications on the randomized OlympiAD clinical trial of 302 patients with HER-2-negative metastatic breast cancer with a germline BRCA mutation who researchers randomly assigned 2:1 to receive olaparib (300 mg orally twice daily) or physician’s choice of capecitabine, vinorelbine or eribulin (Halaven, Eisai) chemotherapy. All patients previously received chemotherapy in the neoadjuvant, adjuvant or metastatic setting.

Results showed olaparib prolonged PFS compared with chemotherapy (7 months vs. 4.2 months; HR = 0.58; 95% CI, 0.43-0.8), which served as the study’s primary efficacy endpoint.

“This class of drugs has been used to treat advanced, BRCA-mutated ovarian cancer and has now shown efficacy in treating certain types of BRCA-mutated breast cancer,” Richard Pazdur, MD. director of the FDA’s Oncology Center of Excellence and acting director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research, said in a press release. “This approval demonstrates the current paradigm of developing drugs that target the underlying genetic causes of a cancer, often across cancer types.”

Common side effects included anemia, neutropenia, leukopenia, nausea, fatigue, vomiting, nasopharyngitis, respiratory tract infection, influenza, diarrhea, arthralgia/myalgia, dysgeusia, headache, dyspepsia, decreased appetite, constipation, and inflammation and stomatitis.

Severe side effects included development of myelodysplastic syndrome/acute myeloid leukemia and pneumonitis.

Olaparib can harm a developing fetus; therefore, women should be advised of potential risk, use effective contraception and not breastfeed.

Olaparib previously received priority review for this indication.

 

The FDA expanded the indication of olaparib to include patients with germline BRCA-mutated, HER-2-negative metastatic breast cancer who were previously treated with chemotherapy.

Olaparib (Lynparza; AstraZeneca, Merck) — a poly ADP-ribose polymerase inhibitor — is indicated for the treatment of patients with BRCA-mutated, advanced ovarian cancer who have received three or more chemotherapy treatments and for the maintenance treatment of patients with recurrent epithelial ovarian, fallopian tube or primary peritoneal cancer whose tumors have completely or partially responded to chemotherapy.

Patients are selected for olaparib therapy based on the BRCAnalysis CDx (Myriad Genetic Laboratories) gene test, which also received expanded indication from the FDA to include detection of BRCA mutations in blood samples from patients with breast cancer.

The FDA based these expanded indications on the randomized OlympiAD clinical trial of 302 patients with HER-2-negative metastatic breast cancer with a germline BRCA mutation who researchers randomly assigned 2:1 to receive olaparib (300 mg orally twice daily) or physician’s choice of capecitabine, vinorelbine or eribulin (Halaven, Eisai) chemotherapy. All patients previously received chemotherapy in the neoadjuvant, adjuvant or metastatic setting.

Results showed olaparib prolonged PFS compared with chemotherapy (7 months vs. 4.2 months; HR = 0.58; 95% CI, 0.43-0.8), which served as the study’s primary efficacy endpoint.

“This class of drugs has been used to treat advanced, BRCA-mutated ovarian cancer and has now shown efficacy in treating certain types of BRCA-mutated breast cancer,” Richard Pazdur, MD. director of the FDA’s Oncology Center of Excellence and acting director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research, said in a press release. “This approval demonstrates the current paradigm of developing drugs that target the underlying genetic causes of a cancer, often across cancer types.”

Common side effects included anemia, neutropenia, leukopenia, nausea, fatigue, vomiting, nasopharyngitis, respiratory tract infection, influenza, diarrhea, arthralgia/myalgia, dysgeusia, headache, dyspepsia, decreased appetite, constipation, and inflammation and stomatitis.

Severe side effects included development of myelodysplastic syndrome/acute myeloid leukemia and pneumonitis.

Olaparib can harm a developing fetus; therefore, women should be advised of potential risk, use effective contraception and not breastfeed.

Olaparib previously received priority review for this indication.