Olaparib Approval Expands Breast Cancer Treatment Options

The FDA based its approval on OlympiA trial data, which show the PARP inhibitor has the ability to reduce risks of invasive breast cancer recurrence, second cancers, and death, and to improve overall survival.

Lynparza (olaparib; AstraZeneca/Merck) has been approved by the FDA for the adjuvant treatment of deleterious/suspected deleterious germline BRCA-mutated (gBRCAm), human epidermal growth factor receptor 2 (HER2)-negative high-risk early breast cancer in adult patients who have received adjuvant or neoadjuvant chemotherapy.

This latest indication for olaparib adds to excitement about the poly (ADP-ribose) polymerase (PARP) inhibitor, which is also being investigated for use in prostate cancer and has current indications in the United States, European Union, and Japan for ovarian cancer, gBRCAm HER-2 negative metastatic breast cancer following chemotherapy, and gBRCAm HER-2 negative hormone receptor–positive metastatic breast cancer following endocrine therapy.

An additional indication in the EU and Japan is for patients with locally advanced breast cancer.

“This important approval gives early-stage high-risk breast cancer patients in the US with a germline BRCA mutation a new targeted therapy option in the adjuvant setting starting today. Lynparza reduced the risk of disease recurrence in these patients, and now new data confirm it also significantly extended patients’ lives versus placebo,” said Dave Fredrickson, executive vice president, oncology business unit, AstraZeneca, in a statement. “These data underline the importance of germline BRCA testing as soon as possible after diagnosis to help identify patients who may be eligible for Lynparza.”

The FDA based its approval on updated data from the randomized, double-blind, placebo-controlled international OlympiA trial, which show the PARP inhibitor has the ability to reduce risks of invasive breast cancer recurrence, second cancers, and death, and to improve overall survival. Data were first presented at the 2021 American Society of Clinical Oncology Annual Meeting, from among 1836 patients.

With primary and secondary end points of invasive disease-free survival (IDFS) and overall survival, respectively, statistically significant improvements were seen for both compared with placebo:

  • 42% reduced risk of IDFS (HR, 0.58; 95% CI, 0.46-0.74; P < .0001)
  • 32% reduced risk of death (HR, 0.68; 95% CI, 0.50-0.91; P = .0091)

For this study, the authors defined IDFS as, “time from randomization to the date of the first loco-regional or distant recurrence or new cancer or death from any cause.”

The most common adverse events overall in OlympiA were nausea (57%), fatigue (42%), and anemia (24%), with top grade 3 AEs being anemia (9%), neutropenia (5%), and leukopenia (3%). Thirty-one percent of trial participants required dose interruptions and 23% required dose reductions, with anemia being cited as the most common reason in both cases, at 11% and 8%, respectively. An additional 10% discontinued olaparib treatment, most because of nausea (2%).

OlympiA’s treatment protocol comprised 1 year of 300-mg twice-daily olaparib administered orally vs placebo—this is also the recommended olaparib dose—and to be included in the trial patients had to have a history of at least 6 cycles of neoadjuvant or adjuvant chemotherapy containing anthracyclines, taxanes, or both.

Close to twice as many events were seen in the placebo vs olaparib arm (20% vs 12%), with IDFS at 3 years in the treatment arm besting the placebo arm by 9 percentage points: 86% vs 77%. In addition, the treatment arm had a third fewer deaths: 75 (8%) vs 109 (12%).

These results are especially noteworthy because breast cancer is the most diagnosed cancer worldwide and they highlight the importance of genetic testing among women with high-risk breast cancer disease, to increase their targeted treatment options. Inherited breast cancers are typically more aggressive and deadly, despite their 5% to 10% occurrence as a breast cancer, and women with BRCA mutations have a 72% lifetime risk of breast cancer vs 12% for women overall.

BRCA mutations cause cell instability because they inhibit cell repair by inhibiting protein production or preventing its proper function. The result is a greater likelihood of developing cancer-related genetic alterations.