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The European Medicines Agency’s Committee for Medicinal Products for Human Use has recommended the approval of olaparib for the adjuvant treatment of patients with germline BRCA-mutated, HER2-negative, high-risk, early breast cancer who have received neoadjuvant or adjuvant chemotherapy.
The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended the approval of olaparib (Lynparza) for the adjuvant treatment of patients with germline BRCA-mutated, HER2-negative, high-risk, early breast cancer who have received neoadjuvant or adjuvant chemotherapy.1
The positive opinion is based on primary findings from the phase 3 OlympiA trial (NCT02032823) presented during the 2021 ASCO Annual Meeting and published in the New England Journal of Medicine in June 2021.1,2
Results from this analysis demonstrated a statistically significant and clinically meaningful improvement in the primary end point of invasive disease-free survival (iDFS), reducing the risk of invasive breast cancer recurrences and second cancers or death by 42% vs placebo (HR, 0.58; 99.5% CI, 0.41-0.82; P < .0001).
Overall survival (OS) data, which were presented in March 2022 at the European Society for Medical Oncology Virtual Plenary, showed olaparib demonstrated a statistically significant and clinically meaningful improvement in the key secondary end point of OS, reducing the risk of death by 32% vs placebo (HR, 0.68; 98.5% CI, 0.47-0.97; P = .0091).
“For patients with high-risk, early-stage breast cancer, the risk of recurrence remains unacceptably high, and cancer will return for more than one in four of these patients. [This] recommendation is hopeful news for patients in Europe, as we move closer to setting a potential new standard of care that improves OS in patients suitable for treatment with olaparib,” Andrew Tutt, MD, PhD, global chair of the OlympiA trial and professor of Oncology at The Institute of Cancer Research, London and King’s College London, stated in a press release.
In March 2022, the FDA approved olaparib for the adjuvant treatment of patients with germline BRCA-mutated, HER2-negative, high-risk early breast cancer who have previously received chemotherapy either before or after surgery, which was also based on the findings from OlympiA.3
The multicenter, double-blind, parallel-group, placebo-controlled, international trial evaluated the efficacy and safety of olaparib vs placebo as adjuvant treatment in patients with germline BRCA-mutant, HER2-negative, high-risk early breast cancer following definitive local treatment and neoadjuvant or adjuvant chemotherapy.
OlympiA enrolled 1836 patients with HER2-negative breast cancer harboring a germline BRCA mutation. Patients were randomized 1:1 to receive 300 mg of oral olaparib twice daily for 1 year (n = 921) or placebo (n = 915). Additionally, patients had to have been treated for stage II or III breast cancer, and have completed surgery and chemotherapy, with or without radiotherapy.
Inclusion criteria also required that patients have a high risk of disease recurrence. Those who had received prior treatment with a PARP inhibitor were not eligible for enrollment.
The primary endpoint was iDFS, defined as the time from randomization to the date of the first locoregional or distant recurrence or new cancer or death from any cause. Secondary end points included distant disease-free survival, OS, health-related quality of life, and safety.
“If approved, [olaparib] will provide a new targeted treatment option for patients with germline BRCA-mutated, HER2-negative, early breast cancer in Europe. By treating patients as early as possible in their disease, we hope to avoid life-threatening recurrence and give people more time with their loved ones,” Susan Galbraith, executive vice president of Oncology R&D at AstraZeneca, stated in a press release.
The safety and tolerability profile of olaparib in OlympiA was in line with that observed in prior studies. The most common adverse effects (AEs) occurring in at least 10% of patients who received olaparib were nausea (57%), fatigue (42%), anemia (24%), vomiting (23%), headache (20%), diarrhea (18%), leukopenia (17%), neutropenia (16%), decreased appetite (13%), dysgeusia (12%), dizziness (11%) and stomatitis (10%).
The most common grade 3 or greater AEs for olaparib were anemia (9%), neutropenia (5%), leukopenia (3%) and fatigue (1.8%). Approximately 10% of patients who received olaparib discontinued treatment due to an AE.
“Patients with germline BRCA-mutated, HER2-negative early breast cancer will often develop breast cancer at an earlier age than those without BRCA mutations, impacting people in their prime. Today’s positive opinion brings us closer to our goal of offering a much-needed new treatment option to these patients in Europe,” Eliav Barr, MD, senior vice president, head of Global Clinical Development, and chief medical officer of Merck Research Laboratories, stated in a press release.