FDA approves Lynparza for new breast cancer indication
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The FDA expanded the approval of olaparib to include a new breast cancer indication.
The approval applies to use of the agent as adjuvant treatment for patients with germline BRCA-mutated, HER2-negative high-risk early breast cancer who received chemotherapy in the neoadjuvant or adjuvant settings.
Olaparib (Lynparza; AstraZeneca, Merck) is a poly(ADP-ribose) polymerase (PARP) inhibitor approved in the United States for multiple cancer indications.
The FDA based the new indication on results of the randomized phase 3 OlympiA study, which included 1,836 patients with germline BRCA-mutated, HER2-negative, stage II to stage III breast cancer who underwent surgery. Patients received standard neoadjuvant (50.1%) or adjuvant (49.9%) chemotherapy with or without radiotherapy, and all patients were deemed at high risk for cancer recurrence.
Researchers randomly assigned patients 1:1 to receive 1 year of continuous treatment with 300 mg oral olaparib twice daily (n = 921; median age, 42 years; range, 36-49) or placebo (n = 915; median age, 43 years; range, 36-50).
Invasive DFS — which included local or metastatic recurrence, other new cancers and death of any cause — in the intent-to-treat population served as the study’s primary endpoint. Secondary endpoints included distant DFS, OS and safety.
As Healio previously reported, results showed olaparib reduced risk for invasive breast cancer recurrence, second cancers or death by 42% compared with placebo (HR = 0.58; 95% CI, 0.46-0.74).
Olaparib also appeared associated with a 32% reduced risk for death (HR = 0.68; 95% CI, 0.5-0.91), as well as an improvement in 3-year DFS (85.9% vs. 77.1%; difference, 8.8 percentage points; 95% CI, 4.5-13).
Olaparib exhibited a safety profile consistent with that observed in prior trials.
The most common adverse events observed among olaparib-treated patients included nausea (57% for olaparib vs. 23% for placebo), fatigue (42% vs. 28%), anemia (24% vs. 3.9%), vomiting (23% vs. 8%), headache (20% vs. 17%), diarrhea (18% vs. 14%), leukopenia (17% vs. 6%), neutropenia (16% vs. 7%), decreased appetite (13% vs. 6%), dysgeusia (12% vs. 4.8%), dizziness (11% vs. 7%) and stomatitis (10% vs. 4.5%).
The most common grade 3 or higher adverse events in the olaparib group included anemia (9%), neutropenia (5%), leukopenia (3%) and fatigue (1.8%).
Thirty-one percent of patients assigned olaparib required dose interruptions due to adverse events; 23% required dose reductions for the same reason, and 10% discontinued olaparib treatment due to adverse events.
“[This] approval of olaparib is great news for patients with a specific inherited form of breast cancer. Most breast cancers are identified in the early stages, and many patients will do very well, but for those with higher-risk disease at diagnosis, the risk of cancer returning can be high, and new treatment options are needed,” Andrew Tutt, MD, global chair of the OlympiA trial and professor of oncology at The Institute of Cancer Research and King’s College London, said in a Merck-issued press release. “OlympiA has shown that identifying a [BRCA1/BRCA2] mutation in women with high-risk disease opens the additional option of eligibility for olaparib treatment, which reduced the risk of recurrence and improved survival for these patients.”
The FDA also approved the BRACAnalysis CDx test (Myriad Genetics) as a companion diagnostic to identify patients with germline BRCA-mutated HER2-negative, high-risk early-stage breast cancer who may benefit from olaparib.
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