Adjuvant olaparib after adjuvant or neoadjuvant chemotherapy improves outcomes in patients with germline BRCA1/2 mutations and high-risk, HER2-negative early breast cancer, according to the second prespecified analysis of the phase 3 OlympiA trial.1

Olaparib improved overall survival (OS), invasive disease-free survival (IDFS), and distant disease-free survival (DDFS), compared with placebo.

These results were presented in an ESMO Virtual Plenary presentation by Andrew Tutt, MB ChB, PhD, of the Institute of Cancer Research in London, United Kingdom.


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OlympiA is the first phase 3 trial (ClinicalTrials.gov Identifier: NCT02032823) designed to evaluate the efficacy of a PARP inhibitor as adjuvant therapy in patients with germline BRCA-mutated, HER2-negative, high-risk early breast cancer.

The double-blind study enrolled 1836 patients. Those in the neoadjuvant group received 6 or more cycles of neoadjuvant chemotherapy, followed by surgery, with or without radiotherapy. Those in the adjuvant group underwent surgery and then received 6 or more cycles of adjuvant chemotherapy, with or without radiotherapy.

Patients in the neoadjuvant and adjuvant groups were randomly assigned to receive olaparib (n=921) or placebo (n=915), both taken twice daily for 1 year. Baseline characteristics were similar between the treatment arms.

Results of the first preplanned interim analysis, with a median follow-up of 2.5 years, showed significant improvement in the IDFS and DDFS outcomes with olaparib compared with placebo (both P <.001).2 However, the OS difference did not meet the prespecified level for significance.

At the second interim analysis, the median follow-up was 3.5 years.1 The 4-year OS rate was 89.8% in the olaparib arm and 86.4% in the placebo arm (hazard ratio [HR], 0.68; 98.5% CI, 0.47-0.97; P =.009).

The improvements observed in IDFS and DDFS were sustained with the longer follow-up. The 4-year IDFS rate was 82.7% in the olaparib arm and 75.4% in the placebo arm (HR, 0.63; 95% CI, 0.50-0.78). The DDFS rate was 86.5% and 79.1%, respectively (HR, 0.61; 95% CI, 0.48-0.77).

The safety data remained consistent with the known side effects of olaparib, according to Dr Tutt. Grade 3 or higher adverse events observed in more than 1% of patients treated with olaparib included anemia (9%), neutropenia (5%), leukopenia (3%), and fatigue (2%).

There was no increase in the incidence of serious adverse events, and there were no new cases of myelodysplastic syndromes or acute myeloid leukemia with olaparib.

“Olaparib after local treatment and neoadjuvant or adjuvant therapy significantly improved IDFS, DDFS, and OS with limited and manageable toxicity and without new safety signals,” Dr Tutt concluded. “Germline BRCA1 and BRCA2 sequencing is an important companion diagnostic for adjuvant treatment decisions in breast cancer.”

Disclosures: This research was supported by AstraZeneca in collaboration with Merck & Co., Inc., Myriad Genetic Laboratories, Inc., and other organizations. Dr Tutt and colleagues declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.

References

  1. Tutt ANJ, Garber J, Gelber RD, et al. Pre-specified event driven analysis of overall survival (OS) in the OlympiA phase III trial of adjuvant olaparib (OL) in germline BRCA1/2 mutation (gBRCAm) associated breast cancer. Presented at 2022 ESMO Virtual Plenary Series; March 16, 2022. Abstract VP1-2022.
  2. Tutt ANJ, Garber JE, Kaufman B, et al. Adjuvant olaparib for patients with BRCA1- or BRCA2-mutated breast cancer. N Eng J Med. 2021;384(25):2394-2405. doi:10.1056/NEJMoa2105215