FDA’s Extension of Lynparza Approval an ‘Exciting Thing’ for Certain Patients With Breast Cancer

The Food and Drug Administration’s (FDA) recent decision to extend the approved indication of Lynparza (olaparib) gives patients with germline BRCA-mutated HER2-negative high-risk early-stage breast cancer a uniquely sensitive drug option that can target the cancer while leaving normal cells alone, according to an expert.

“We really like that the unique sensitivity is only there for patients who have these germline mutations,” Dr. Charles Geyer, co-director of University of Pittsburgh Medical Center’s National Clinical Trials Network and chief scientific officer of the National Surgical Adjuvant Breast and Bowel Project Foundation, said in an interview with CURE®. “It’s an exciting thing for them. (For the patient it is like), ‘the thing that caused us to get cancer, now we have an effective therapy specific to that that helps us have a much better likelihood of (having an) outcome.’”

The FDA first approved Lynparza in 2018 for the treatment of patients with BRCA-positive, HER2-negative metastatic breast cancer who have previously received chemotherapy. The extended indication is for an additional group of patients with early-stage breast cancer who were previously treated with chemotherapy before or after surgery to remove the affected tumors. Moreover, the recent approval is indicated for patients with early-stage disease who are at a high risk for disease recurrence.

The agency’s most recent decision to OK the expanded label indication was based on data from the phase 3 OlympiA trial. The findings from this trial showed that treatment with Lynparza (921 patients) reduced the risk of invasive breast cancer recurrences, second cancers or death by 42% versus placebo (915 patients). Additionally, newly released data showed that the study drug reduced the risk of death by 32% when compared with placebo.

Of note, the extended approval of Lynparza is indicated for use in the adjuvant setting, meaning additional treatment given to a patient after they had already received primary treatment.

In the trial, patients had already received chemotherapy, underwent surgery to remove the tumor or were administered radiation therapy. Then, they were randomized to received either a year of Lynparza or placebo.

The goal, according to Geyer, was to see if more therapy after initial treatment would improve patient outcomes and reduce the risk of disease recurrence.

At three years of follow-up, Geyer noted, the invasive disease free survival (defined as treatment that keeps the patient alive without a recurrence of disease) rate was 77% in patients who received placebo after initial treatment. That rate jumped to 86% in the group that received Lynparza for up to a year.

He also explained that invasive disease free survival outcomes, meaning the patient remained alive without the disease spreading to distant organs such as the liver, were more favorable in those who were randomized to receive Lynparza (88% versus 81%).

Side effect profile

Geyer said that 24% of patients who received Lynparza reported experiencing side effects that are considered severe and interfere with a person’s ability to do normal daily activities (known as grade 3). Although this was an increase in occurrence from the 11% of patients in the placebo group, he noted that the real focus should be on the fact that 76% of patients on Lynparza didn’t experience a grade 3 event.

“We had to reduce the dose in only one in four patients,” he said. “So, three out of four patients tolerated the starting dose just fine.”

One of the most common side effects, he explained, was nausea. More than half (57%) of the patients who were treated with Lynparza reported experiencing the side effect. However, Geyer mentioned, the nausea tended to be mild in nature and patients were advised to consume a light meal while taking their medication.

There were also some cases of anemia, which occurred in approximately 24% of patients. Geyer explained that patients should be monitored with routine bloodwork since anemia can be associated with an increase in fatigue. However, most of the cases were manageable.

“Only 6% of patients had to receive a blood transfusion,” he said. “And when they (needed a transfusion), only 2% had more than one.”

Goal of treatment

The study results that led the FDA to approve this recent indication, as Geyer said, are all very important clinical benefits for patients with germline BRCA-mutated HER2-negative high-risk early-stage breast cancer.

He said that he tells his patients that the goal of therapy is to do everything in his power that is reasonable to push the patient’s chance for staying cancer free as high as possible.

And although Geyer noted that surgery alone can cure some patients, he said that’s not always the case for a small subset of patients with aggressive types of breast cancer. That’s why the results that led to this approval are promising.

“The combination of the efficacy and the safety data, (allows) us to say this is really quite reasonable for patients to consider,” he concluded.

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