Olaparib well tolerated in people with early-stage BRCA+, HER2- disease

Early results of a quality-of-life study presented on December 10 at the San Antonio Breast Cancer Symposium found that olaparib did not worsen or prolong side effects when given after chemotherapy for BRCA+, HER2-, high-risk, early-stage breast cancer.

Background

Around 5 to 10  percent of breast cancers are linked to changes in the BRCA 1 or 2 genes. These changes (mutations) are passed down through families. Genetic testing is used to identify people who have the genetic mutation (described as BRCA+). People who are BRCA+ have a higher risk of breast, ovarian, pancreatic, and prostate cancers.

Research focuses on preventing, finding early, and treating BRCA+ cancers. Medicines showing the most success are PARP inhibitors, a type of targeted therapy.

In 2018, the U.S. Food and Drug Administration approved the PARP inhibitor olaparib (Lynparza) for BRCA+, HER2- metastatic breast cancer. It was the first medicine approved specifically for BRCA+ cancer. This approval was based on the phase III OlympiAD trial of people with BRCA+ metastatic breast cancer.

In 2021, early results from the phase III OlympiA trial showed that olaparib given after chemotherapy extended the time participants were disease-free. This trial included people with BRCA+, HER2-, high-risk, early-stage cancer.

Chemotherapy works by attacking fast-growing cancer cells. In doing so, it can kill healthy cells sometimes causing side effects like hair loss, mouth sores, nausea, and fatigue. In people with early-stage breast cancer, fatigue can be very debilitating and delay recovery by one to two years. The study team looked at whether the addition of olaparib would lengthen the recovery time even more.

Results

Researchers looked at the impact of olaparib after standard treatment for high-risk, early-stage BRCA+ breast cancer on quality of life. The OlympiA trial participants completed surveys at the start of the study and again following treatment with olaparib or a placebo. The results are based on patient reported outcomes (PRO).

The OlympiA trial had 1,836 participants. Of these, 1,535 make up the quality-of-life study group. Eighty-five were excluded for lack of consent, failure to start treatment, and related reasons. An additional 216 did not complete follow-up surveys. The group was representative of the larger study in age, race, and geography.

In general, olaparib was well tolerated. People taking olaparib had slightly more nausea and vomiting at the 6- and 12-month marks. Fatigue was slightly higher at 6 and 12 months as well, but not enough to be considered clinically meaningful. There was no difference in any of these symptoms at 18 and 24 months. Differences were also not seen in diarrhea, physical functioning, and emotional functioning.

What it means for people with early-stage BRCA+, HER2- disease

We already knew that olaparib after chemotherapy had medical benefit. Now we know it is well tolerated by patients and does not affect quality of life in a way that delays recovery. This is significant news for this high-risk group for whom recurrence is a major concern.

This study had some limitations. For example, we do not know anything about the 216 people who did not participate in follow-up. It is possible they were sicker or in some way unlike the study group.

The study also did not address all quality-of-life topics of interest to women with BRCA-driven early-stage cancer, many of whom are younger. Final results of this research are still to come. Hopefully we will learn more about the possible impact on fertility, sexual health, and other priority concerns.