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Adjuvant Olaparib New Standard for BRCA-Mutated Breast Cancer

Due to the ongoing COVID-19 pandemic, the American Society of Clinical Oncology (ASCO) Annual Meeting was held virtually for the second year in a row. During 4 – 6 June, more than 32,000 participants from around the globe gathered online to hear about the latest results from cutting-edge research on cancer treatments, new technologies, and drug pipelines, and to discuss state-of-the-art multidisciplinary patient care. The theme of ASCO 2021 was ‘Equity: Every Patient. Every Day. Everywhere.’ Among the few thousand abstracts, around 550 were discussed during oral sessions, scientific symposia, and poster discussion sessions. Furthermore, five late-breaking abstracts (LBAs) that may directly impact clinical practice in the near future were presented during the plenary session.

Andrew Tutt, MB, ChB, PhD, FMedSci (The Institute of Cancer Research and King’s College London, UK) presented results from a primary analysis of the global, randomized, placebo-controlled, phase III OlympiA trial (LBA1), which tested adjuvant therapy with the poly (ADP-ribose) polymerase (PARP) inhibitor, olaparib, in BRCA1/2 mutation carriers with high-risk human epidermal growth factor 2 (HER2)-negative early breast cancer after treatment with local therapy and neoadjuvant or adjuvant chemotherapy. The OlympiA trial included 1836 patients who were randomly assigned to receive olaparib (300 mg twice daily) or placebo, for 1 year. They were stratified according to hormone receptor status, timing of previous chemotherapy (neoadjuvant or adjuvant), and prior use of platinum-based chemotherapy. The primary endpoint of the trial was invasive disease-free survival (IDFS), and secondary endpoints included distant disease-free survival (DDFS), overall survival (OS), safety, and quality of life. The median follow-up was 2.5 years for the intention-to-treat (ITT) population.

Treatment with olaparib significantly prolonged IDFS compared with placebo (hazard ratio [HR] 0.58; P<0.0001). At 3 years, 85.9% of patients treated with olaparib were alive and free of invasive disease versus 77.1% with placebo (a difference of 8.8%). Similarly, DDFS was significantly longer in patients receiving adjuvant olaparib (HR, 0.57; P<0.001). At 3 years, 87.5% of patients in the olaparib group were free of distant disease versus 80.4% in the placebo group (a difference of 7.1%). There was also a trend towards improved survival with olaparib, with a 3-year OS difference of 3.7%, but this was not statistically significant. Planned subgroup analysis showed no statistical evidence of a different treatment effect with olaparib in any subgroup compared with the overall ITT population; however, further follow-up is required. The toxicity profile of olaparib was consistent with previous experience. Grade 3 or greater adverse events (AEs) were infrequent: the most common were anemia (7.8%) and neutropenia (4.8%). Importantly, there was no increase in myelodysplastic syndrome or acute myeloid leukemia with olaparib. AEs led to dose reductions in 25% of patients and permanent treatment discontinuation in 9.9% of patients (versus 5.2% and 4.2% with placebo, respectively). There was one death in the olaparib group and two deaths in the placebo group. Treatment with olaparib did not significantly affect global health-related quality-of-life scores.

In his conclusion, Dr Tutt pointed out that the trial provides evidence that germline BRCA1/2 sequencing is an important biomarker for the selection of systemic therapy in early breast cancer. A discussant of the abstract, Dr Nadine Tung, MD (Dana-Farber Harvard Cancer Center, Boston, US) called the data practice-changing, and emphasized the importance of identifying patients with early breast cancer and germline BRCA1/2 mutations in order to guide treatment decisions. She noted that less than 50% of patients are currently being offered genetic testing. Dr Tung also indicated that OlympiA raises several questions, including whether PARP inhibitors should be used for all patients with germline BRCA1/2 mutations, the optimal duration of therapy, whether there is a survival benefit with longer follow-up, and the impact of a longer follow-up on the safety profile of olaparib.

The OlympiA trial results were published in the New England Journal of Medicine.

References

Tutt ANJ, et al. ASCO 2021. Abstract LBA01.

Tutt ANJ, et al. N Engl J Med. 2021 June 3 [Online ahead of print].