Adjuvant Olaparib Approved for BRCA+, High-Risk Early Breast Cancer

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The FDA has approved olaparib (Lynparza) as an earlier line of adjuvant therapy in patients with BRCA-mutated, HER2-negative, high-risk early breast cancer, marking the first approved therapy to treat early, BRCA-mutated cancer.

The BRCA1- and BRCA2-mutated population has been established as an especially at-risk population for aggresive and recurrent breast cancers. Olaparibn's earlier line approval may mark a shift in prioritizing the role of genetic testing in the diagnosis and treatment of patients with breast cancer.

“Today’s approval of olaparib is great news for patients with a specific inherited form of breast cancer," Professor Andrew Tutt, global chair of the OlympiA trial and professor of oncology at The Institute of Cancer Research, London and King’s College London, said in a press release.¹

The approval is based on data from the phase 3 OlympiA trial (NCT02032823), in which participants who have previously received chemotherapy treated with olaparib either before or after surgery demonstrated a 42% improvement in invasive disease-free survival (iDFS) compared with placebo (HR, 0.58; 95% CI, 0.46-0.74; P <.0001).^2,3

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Adjuvant olaparib also decreased risk of disease progression or death by 32% compared with placebo (HR, 0.68; 95% CI, 0.50-0.91; P = .0091). Data on OS were presented at the European Society for Medical Oncology (ESMO) virtual plenary on March 16, 2022. There were 75 deaths (8%) in the olaparib arm and 109 deaths (12%) in the placebo arm (HR, 0.68 [95% CI, 0.50-0.91]; P = .0091).⁴

"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 unacceptably high and new treatment options are needed. OlympiA has shown that identifying a BRCA1/2 mutation in women with high risk disease opens the additional option of eligibility for olaparib treatment, which reduces the risk of recurrence and improves survival for these breast cancer patients," Tutt added.¹

The multicenter, randomized, placebo-controlled OlympiA trial 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.

The primary end point for the study was iDFS; secondary end points included distant disease-free survival (DDFS), overall survival (OS), health-related quality of life, and safety.

Additional findings indicated that patients who received olaparib experienced a 43% reduction in DDFS, including metastatic disease, new cancer, and death due to any cause (stratified HR, 0.57; 99.5% CI, 0.39-0.83; P < .0001). The difference in the 3-year DDFS rate between olaparib and placebo was 7.1% (87.5% vs 80.4%, respectively; 95% CI, 3.0%-11.1%).

The therapy was generally well-tolerated, with adverse events (AEs) reported in the olaparib arm consistent with previous data on the therapy. Additionally, olaparib did not increase serious AEs, including hospital admissions or occurrences of other cancers, such as leukemia.

However, grade 3 or higher AEs were reported more often in patients who received olaparib, and included anemia (9%), neutropenia (5%), leukopenia (3%), and fatigue (2%).

The most common AEs of any-grade reported in patients who received olaparib included nausea (57%), fatigue (40%), anemia (23%), vomiting (23%), and headache (20%). The most common AEs of any-grade reported in the placebo arm were fatigue (27%), nausea (23%), headache (17%), diarrhea (14%), and arthralgia (12%).

“This important approval gives early-stage breast cancer patients in the US with a germline BRCA mutation a new targeted therapy option in the adjuvant setting starting today. Lynparza reduces the risk of disease recurrence in these high-risk patients and now new data confirm it also significantly extends patients’ lives versus placebo. These data underline the importance of germline BRCA testing as soon as possible after diagnosis to identify patients that may be eligible for Lynparza," Dave Fredrickson, executive vice president, Oncology Business Unit, AstraZeneca, added to the statement.¹

References

1. Lynparza approved in the US as adjuvant treatment for patients with germline BRCA-mutated HER2-negative high-risk early breast cancer. AstraZeneca. News release. March 11, 2022. Accessed March 11, 2022. https://bit.ly/3tQePcn
2. Tutt ANJ, Garber JE, Kaufman B, et al. Adjuvant olaparib for patients with BRCA1- or BRCA2-mutated breast cancer. N Engl J Med. 2021;384(25):2394-2405. doi:10.1056/NEJMoa2105215
3. Tutt A, Garber JE, Kaufman B, et al. OlympiA: a phase III, multicenter, randomized, placebo-controlled trial of adjuvant olaparib after (neo)adjuvant chemotherapy in patients with germline BRCA1/2 mutations and high-risk HER2-negative early breast cancer. J Clin Oncol. 2021;39(suppl 15):LBA1. doi:10.1200/JCO.2021.39.15_suppl.LBA1
4. FDA approves olaparib for adjuvant treatment of high-risk early breast cancer. News release. ESMO. March 18, 2022. https://www.esmo.org/oncology-news/fda-approves-olaparib-for-adjuvant-treatment-of-high-risk-early-breast-cancer