medwireNews: The OlympiA study has demonstrated a significant reduction in the risk for recurrence and disease progression with adjuvant olaparib versus placebo in patients with HER2-negative, early-stage breast cancer and germline BRCA mutations.
The findings were published in The New England Journal of Medicine to coincide with their presentation at the 2021 ASCO Annual Meeting by Andrew Tutt, from the Institute of Cancer Research in London, UK.
The double-blind phase 3 trial recruited patients with a pathogenic or likely pathogenic BRCA1 or BRCA2 variant who had received definitive local treatment and neoadjuvant or adjuvant chemotherapy for high-risk, HER2-negative primary breast cancer. The majority (around 82%) had triple-negative disease, while the remaining participants were hormone receptor-positive.
Judy Garber reports on the phase 3 OlympiA study suggesting that adjuvant olaparib could be an option for the treatment of patients with early-stage breast cancer and germline BRCA variants (5:00).
In the prespecified event-driven interim analysis, conducted at a median follow-up of 2.5 years, the primary endpoint of invasive disease-free survival (IDFS) was significantly improved for the 921 participants who were randomly assigned to receive the PARP inhibitor olaparib at dose of 300 mg twice daily for up to a year compared with the 915 instead given placebo.
The risk for an invasive disease event was 42% lower for olaparib- than placebo-treated patients and the respective 3-year IDFS rates were 85.9% and 77.1%, giving a between-group difference of 8.8 percentage points.
Olaparib treatment was also associated with a significant distant (D)DFS benefit, with a reduction in the risk for a distant disease event of 43% relative to placebo. The DDFS rates at 3 years were 87.5% and 80.4%, equating to a difference of 7.1 percentage points.
Tutt noted in a press conference that there were fewer deaths in the olaparib than placebo group (n=59 vs 86), but overall survival did not differ significantly between the groups “at this very early timepoint.”
He added that “the side effects of olaparib were consistent with that already known and with the previous studies and the approved labels.”
The incidence of grade 3 or worse adverse events (AEs) was higher in the olaparib than placebo arm, at 24.3% versus 11.3%, with anemia (8.7 vs 0.3%), decreased neutrophil count (4.8 vs 0.8%), decreased white cell count (3.0 vs 0.3%), and fatigue (1.8 vs 0.4%) the most common events.
The rate of serious AEs was comparable between olaparib- and placebo-treated participants, at 8.7% and 8.4%, respectively. And none of the AEs of special interest – including pneumonitis, myelodysplastic syndrome or acute myeloid leukemia – “occurred at a higher frequency in the olaparib group than in the placebo group,” write the study authors, but they stress the need for longer follow-up.
A quarter of patients given olaparib needed a dose reduction compared with 5.2% of those who received placebo, and a respective 9.9% and 4.2% of patients discontinued study treatment permanently.
“These results suggest olaparib for 1 year after standard of care treatments provides meaningful benefit to germline BRCA mutation carriers with high recurrence risk, HER2-negative breast cancer,” commented Tutt.
And he concluded: “They also show that germline testing for BRCA1/2 mutations provides important information that can influence systemic therapy in early breast cancer.”
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2021 ASCO Annual Meeting; 4–8 June
N Engl J Med 2021; doi:10.1056/NEJMoa2105215