|The following article features coverage from the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting. Click here to read more of Cancer Therapy Advisor‘s conference coverage.|
Adjuvant treatment with olaparib after completion of neoadjuvant or adjuvant chemotherapy, significantly improved invasive disease-free survival (IDFS) and distant disease-free survival (DDFS) in patients with germline BRCA1/2 (gBRCA) mutations and high-risk human epidermal growth factor receptor 2 (HER2)-negative early-stage breast cancer, according to new research presented during the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting plenary session.
Olaparib, a poly (ADP-ribose) polymerase (PARP) inhibitor that targets a DNA repair defect is approved for patients with gBRCA mutations and metastatic breast cancer.
Approximately 5% of all patients with breast cancer are carriers of gBRCA mutations. “Outcome is good for many patients with gBRCA mutations and early breast cancer receiving standard treatments but recurrence rates remain high for some and so additional or adjuvant novel targeted treatments are needed,” said lead author Andrew Tutt, FMedSci, FMedSci, PhD, MBChB, who is head of the Division of Breast Cancer Research and director of the Breast Cancer Now Toby Robins Research Centre at the Institute of Cancer Research and Guy’s Hospital King’s College in London.
He discussed the results of OlympiA, which is a first randomized, placebo-controlled, multicenter phase 3 study (ClinicalTrials.gov Identifier: NCT02032823) to investigate the use of olaparib as adjuvant therapy following adjuvant or neoadjuvant chemotherapy in patients with gBRCA mutations and HER2-negative primary breast cancer.
The study enrolled 1836 patients with HER2-negative breast cancer and gBRCA mutations who completed standard treatment (surgery and chemotherapy with or without radiotherapy) but had a high risk of cancer recurrence. Of the enrolled patients, 49.9% received adjuvant chemotherapy and 50.1% received neoadjuvant chemotherapy. Patients were randomly assigned 1:1 to receive either olaparib (921 patients) or placebo (915 patients) for 1 year. The primary endpoint of the study was IDFS in the intention-to-treat population. The secondary endpoints were DDFS, overall survival (OS), safety, and health-related quality of life.
At a median follow-up of 2.5 years, patients treated with olaparib had a longer IDFS than those who received placebo (hazard ratio [HR], 0.58; 99.5% CI, 0.41-0.82; P <.0001). DDFS was significantly longer with olaparib than with placebo (HR, 0.57; 99.5% CI, 0.39-0.83; P <.0001). The 3-year DDFS rate was 87.5% in patients treated with olaparib and 80.4% in patients treated with placebo, indicating a difference of 7.1% (95% CI, 3.0-11.1).
Even though patients treated with olaparib had fewer deaths than those treated with a placebo, the OS was not significantly different between the olaparib and placebo arms at the median follow-up of 2.5 years. Follow-up studies are ongoing.
The most common adverse events in patients treated with olaparib were anemia (8.7%), neutropenia (4.8%), leukopenia (3.0%), fatigue (1.8%), and lymphocytopenia (1.2%). Compared to placebo, olaparib did not increase serious adverse events (SAEs) and adverse events of special interest (AESI). The rate of SAE in patients within the olaparib and placebo arms were 8.7% and 8.4%, respectively. AESI occurred in 2.6% of patients in the olaparib arm and 4.6% of patients in the placebo arm.
“Patients who received olaparib after surgery and chemotherapy were more likely to be alive without cancer and avoid metastasis than the patients who received placebo,” said Dr Tutt.
“Olympia’s findings highlight the need for genetic testing for BRCA mutations in patients diagnosed with high-risk, early-stage breast cancer. These results could have an important impact on treatment decisions for this patient population, possibly including the use of a PARP inhibitor in the adjuvant setting,” said Lori J. Pierce, MD, FASTRO, FASCO, the president of ASCO during a press briefing.
Disclosure: The study was funded by the National Cancer Institute and, Pharmaceutical/Biotech Company OlympiA, which is a partnership between Breast International Group (BIG), NRG Oncology, the US National Cancer Institute (NCI), Frontier Science & Technology Research Foundation (FSTRF), AstraZeneca and MSD. The trial is sponsored by NRG Oncology in the United States and by AstraZeneca outside the United States. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.
Read more of Cancer Therapy Advisor’s coverage of the 2021 ASCO Annual Meeting by visiting the conference page.
Tutt A, Garber JE, Kaufman B, et al. OlympiA: A phase III, multicenter, randomized, placebo-controlled trial of adjuvant olaparib after (neo)adjuvant chemotherapy in patients with germline BRCA1/2 mutations and high-risk HER2-negative early breast cancer. J Clin Oncol.2021;39: (suppl 15; abstr LBA1). doi:10.1200/JCO.2021.39.15_suppl.LBA