Olaparib Improves Progression-Free Survival in BRCA-Associated Breast Cancer


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The PARP INHIBITOR olaparib (Lynparza) improved progression-free survival in women with HER2-negative metastatic breast cancer that was either hormone receptor–positive or triple-negative in patients who had a germline BRCA mutation.1,2 These results of the international, randomized, open-label, phase III OlympiAD trial suggest olaparib could become a new treatment option for BRCA-associated metastatic breast cancer.

For the primary endpoint, median progression-free survival was 7 months with olaparib vs 4.2 months with chemotherapy, representing a 42% improvement that was highly statistically significant (P = .0009).

Mark E. Robson, MD

Mark E. Robson, MD

“This is the first demonstration of improved outcomes with a PARP inhibitor compared with standard treatment in women with BRCA-associated breast cancer,” said lead author Mark E. Robson, MD, Clinic Director of the Clinical Genetics Service and medical oncologist at Memorial Sloan Kettering Cancer Center in New York. “It is especially encouraging to see that olaparib was effective against triple-negative breast cancers that arise in women with inherited germline BRCA mutations, a type of breast cancer that is particularly difficult to treat and often occurs in younger women.”

The study was published online in The New England Journal of Medicine2 to coincide with the presentation during the Plenary Session at the 2017 ASCO Annual Meeting.1

See Mark E. Robson, MD, interviewed on The ASCO Post Newsreels. 

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Olaparib is one of three PARP inhibitors approved by the U.S. Food and Drug Administration (FDA) for the treatment of BRCA-associated ovarian cancer that failed to respond to previous treatments. No PARP inhibitor has been approved for the treatment of breast cancer.

Study Details

The OlympiAD trial randomized 302 patients in a 2:1 ratio to receive olaparib tablets (n = 205) or standard chemotherapy (n = 97), which was physician’s choice among capecitabine, eribulin (Halavan), or vinorelbine. Patients had failed to respond to prior anthracycline and taxane and had received more than two chemotherapies for metastatic disease. At baseline, patients were evenly split between hormone receptor–positive and triple-negative breast cancer. The minority had de novo metastatic breast cancer.

Dr. Robson explained that the dose of the olaparib tablet used in the trial (300 mg twice daily) was different from the FDA-approved dose of 400 mg twice daily because the drug was administered in a new tablet formulation that provides similar drug exposure but is more convenient for patients than the currently available capsule formulation.

Olaparib in Metastatic Breast Cancer

  • Olaparib improved progression-free survival in BRCA-associated metastatic breast cancer compared with chemotherapy, with fewer side effects and improved quality of life.
  • Overall survival data are not yet mature and are awaited.
  • Further study is needed to define biomarkers for benefit.

Overall survival data are not yet mature. At press time, median overall survival was similar in both arms—19.3 months with olaparib and 19.6 months with chemotherapy. Overall survival will be presented when 60% of expected deaths occur. The time to investigator-assessed second disease progression or death was 13.2 months with olaparib vs 9.3 months with chemotherapy, reflecting a 43% improvement favoring olaparib (P = .0033). The objective response rate also favored olaparib—60% vs 29% for chemotherapy—and the complete response rate was 9% vs 2%, respectively.

At the time of data cutoff, 82% discontinued treatment in the olaparib arm vs 97% in the chemotherapy arm. The median duration on treatment was twice as long with olaparib than chemotherapy: 8.2 vs 3.4 months.

Fewer grade 3 or higher adverse events were reported on the olaparib arm: 36.6% vs 50.5% for patients treated with chemotherapy. Grade 3 or higher anemia was more common with olaparib, whereas grade 3 or higher neutropenia was more frequently reported in the chemotherapy arm.

Patients taking olaparib had an improved quality of life compared with those on chemotherapy. On the European Organisation for Research and Treatment of Cancer 30-item core quality-of-life questionnaire, a 7.5-point difference favored olaparib (P = .0035).

Additional Commentary

At a press conference, ASCO President Daniel F. Hayes MD, commented on the OlympiAD trial: “This represents a major step forward in translational medicine for HER2-negative breast cancer,” he stated. He noted that the study population was confined to women with inherited BRCA mutations, so results are not generalizable to the general population. “But if we use it in this precise population,” he said, “olaparib has fewer side effects and works better than chemotherapy. It makes patients feel better, and hopefully they will live longer.”

He continued, “Studies in combination are ongoing now. This study is the first step. I believe we will see trials of this drug earlier in the course of disease and in the adjuvant setting. We will need to know long-term toxicity and understand the mechanisms of resistance.” ■

DISCLOSURE: Drs. Robson and Hayes reported no conflicts of interest.

REFERENCES

1. Robson ME, et al: OlympiAD: Phase III trial of olaparib monotherapy versus chemotherapy for patients with HER2-negative metastatic breast cancer and germline BRCA mutation. 2017 ASCO Annual Meeting. Abstract LBA4. Presented June 4, 2017.

2. Robson ME, et al: Olaparib for metastatic breast cancer in patients with a germline BRCA mutation. N Engl J Med. June 4, 2017 (early release online).


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Formal discussant of this paper, Allison Kurian, MD, MSc, of Stanford University School of Medicine, said: “I think these results are practice-changing. Toxicity and quality of life were better with olaparib [Lynparza].”

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