Targeted therapy for BRCA-related cancer reduces recurrence in early-stage breast cancer

PARP inhibitor olaparib lowered the risk of cancer returning in people with inherited BRCA mutations, raising importance of genetic testing for people with early-stage breast cancer
ASCO Coverage
Breast Cancer News
June 8, 2021
By: 
Eric Fitzsimmons, Copy Editor and Content Coordinator

Results from the phase III OlympiA trial found that adding the PARP inhibitorinfo-icon olaparib (Lynparza) to treatment for people with inherited mutations in the genes BRCA1 or BRCA2 who have been diagnosed with stageinfo-icon II or III, HER2-negative breast cancer resulted in fewer cases of cancer returning after 3 years.

Results from the OlympiA trial were presented on June 6 as part of the American Society of Clinicalinfo-icon Oncologyinfo-icon Annual Meeting. Doctors discussing the results say they will change the way doctors treat early-stage breast cancers in people with an inheritedinfo-icon BRCA mutationinfo-icon. The findings also highlight the importance of genetic testing for an inherited mutation, with results now having a direct impact on treatment decisions.

Background

Certain inherited mutations, or changes, in genes known as BRCA1info-icon and BRCA2info-icon put a person at a higher risk of developing breast and ovarian cancerinfo-icon. It is not currently recommended that everyone diagnosed with breast cancer get genetic testinginfo-icon that identifies mutations including those in the BRCA genes. These geneticinfo-icon changes are inherited from your parents and certain factors, such as a family history of breast cancer, being diagnosed at a young age, and having family members test positive for a BRCA mutation, may lead your doctor to recommend genetic testing. Knowing about a BRCA mutation may influence surgical decisions to limit the risk of a future cancer diagnosisinfo-icon. PARPinfo-icon inhibitors are the first medicines to be approved to specifically treat breast cancer in people with an inherited BRCA mutation, but have not been used in early-stage breast cancerinfo-icon.

Olaparibinfo-icon is a PARP inhibitor approved to treat people who have inherited BRCA mutations and a metastaticinfo-icon breast cancer diagnosis that is HER2-negative. PARP inhibitors can cause cancer cells to die by stopping an enzyme in the body, known as poly (ADP-ribose) polymerase, or PARP, from repairing cancer cellinfo-icon DNA in people with BRCA mutations. Olaparib is a pill, usually taken twice a day, at least 12 hours apart.

The OlympiA study looked at adding olaparib to standard treatment in people with certain breast cancers that had a high risk of returning. Participants in the study had

  • a diagnosis of stage II or stage III breast cancerinfo-icon
  • breast cancer that was either hormone receptorinfo-icon-positive and HER2-negative or triple negative
  • tested positive for an inherited mutation on the BRCA1 or BRCA2 geneinfo-icon
  • finished treatment including surgeryinfo-icon, chemotherapyinfo-icon (given either before or after surgery), and radiation therapyinfo-icon, if recommended by their medical team
  • cancer with certain features that indicate a high risk of cancer returning:
    • They were given chemotherapy before surgery and there were still signs of cancer at the time of surgery.
    • They were given chemotherapy after surgery and had a large tumorinfo-icon or multiple lymphinfo-icon nodes with signs of cancer.

The study’s 1,836 participants were randomly assigned to one of two trial treatments:

  • One year of olaparib pills, taken twice daily.
  • One year of placeboinfo-icon pills, taken twice daily.

Participants with hormone receptor-positive breast cancer could take hormonal therapyinfo-icon along with olaparib.

The primary endpointinfo-icon, the measurement researchers use to see if olaparib worked better than placebo in this setting, was invasive disease-free survival, the rate of people who did not have cancer return in the study period.

Results

Early results from the OlympiA trial found that people given olaparib were less likely to have cancer return after 3 years than were people given a placebo.

The chance that a person was living without cancer returning 3 years after starting the OlympiA study was

  • 85.9 percent for people given olaparib
  • 77.1 percent for people given placebo

The difference was statistically significantinfo-icon, meaning that it was not likely caused by chance.

The study also found a statistically significant difference in the rate of people who were living without breast cancer traveling to other parts of the body after 3 years:

  • 87.5 percent of people given olaparib.
  • 80.4 percent of people given placebo.

OlympiA also found that people given olaparib were less likely to die of any cause after 3 years than were people given placebo, but this difference was not statistically significant. The overall survival data presented here followed patients for a medianinfo-icon of 2.5 years, but it is common for data on overall survival to take longer before showing a difference that is statistically significant. The OlympiA trial is ongoing and researchers will continue to follow participants to see if adding olaparib to treatment really leads to living longer.

People taking olaparib experienced side effects that researchers expected with this medicineinfo-icon. The most common side effects reported on olaparib were

  • nauseainfo-icon — experienced by 57 percent of participants
  • fatigueinfo-icon — experienced by 40 percent of participants
  • anemiainfo-icon — experienced by 24 percent of participants

Most of the cases for these side effects were gradeinfo-icon 1 or 2, meaning they are considered mild or moderate and do not need hospital care. Most side effects of grade 3 or higher were anemia and neutropeniainfo-icon, meaning there were low counts of certain types of blood cells.

What this means for you

The results of OlympiA were featured in the plenary session, which highlights the most notable findings of the ASCO Annual Meeting, and are expected to change how doctors treat early-stage breast cancer. If you are in active treatment now, have an inherited BRCA mutation, and meet the other requirements, your doctor may recommend adding olaparib to your treatment plan. These were early results, and some questions are still being studied, including the effect on overall survival and whether all the subgroups in this population benefit equally. But Nadine Tung, MD, who discussed the findings and the changing role of PARP inhibitors as a result, says the large difference in rates of cancer returning make it very likely that olaparib will appear in doctors’ practices soon.

Additionally, the fact that treatment with olaparib is linked to a person’s having a BRCA mutation may change how we look at genetic testing for an inherited mutation. According to Dr. Tung, less than half the people who guidelines recommend should get genetic testing actually get it. Minority populations and underserved communities are among the least likely to get genetic testing for an inherited mutation currently.

Until now, genetic testing for an inherited mutation could guide decisions about lowering your risk of future cancer. But with the OlympiA results, a positive BRCA result can affect your treatment now. These findings make it more important that people recommended for genetic testing for inherited mutations be identified and referred for those tests. Dr. Tung says that this study may shift that perspective even further, from the practice of giving genetic tests only to people with certain backgrounds toward expecting genetic testing to almost everyone diagnosed with early-stage breast cancer.

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