medwireNews: Updated results from the OlympiA trial indicate that use of adjuvant olaparib significantly improves overall survival (OS) compared with placebo for patients with HER2-negative, early-stage breast cancer who have germline BRCA1/2 mutations.
The second prespecified analysis from the phase 3 study was presented at the ESMO Virtual Plenary by Andrew Tutt (Institute of Cancer Research, London, UK).
The first interim analysis, after a median 2.5 years of follow-up, showed that use of the adjuvant PARP inhibitor after definitive local therapy and neoadjuvant or adjuvant chemotherapy for high-risk disease was associated with a significant improvement in both invasive and distant disease-free survival (DFS) but did not demonstrate a significant gain in OS.
The current, second interim analysis, after a median 3.5 years of follow-up, now shows a significant improvement in OS with olaparib 300 mg twice daily for 1 year (n=921) versus placebo (n=915), with 4-year rates of 89.8% versus 86.4% and a hazard ratio (HR) for death of 0.68.
Tutt explained that the OS subgroup analysis “remains constrained by low numbers of events at what remains short follow-up” but the OS benefit of adjuvant olaparib use was “consistent and without evidence of significant heterogeneity across major subgroups” including chemotherapy regimen and BRCA1/2 and hormone receptor status.
In addition, the updated invasive DFS finding with a HR of 0.63 in favor of olaparib use was “consistent with previous estimates” and had “tightening confidence intervals,” the presenter said. A similar pattern was also found for the updated distant DFS findings, with a HR of 0.61, and subgroup analyses for both invasive and distant DFS were again “consistent” in favor of olaparib use.
The safety profile was in line with that previously reported for olaparib, with grade 3 or more serious adverse events (AEs) occurring in 24.5% of olaparib-treated patients and 11.3% of controls. Nausea, anemia, and fatigue were associated with permanent treatment discontinuation, with discontinuation rates of 10.8% and 4.6% in the olaparib and control arms, respectively.
There were no new or excess cases of the special interest AEs of myelodysplastic syndrome or acute myeloid leukemia, pneumonitis, and new primary malignancies in the olaparib arm, nor any AEs leading to death since the initial report, the presenter added.
“Olaparib after local treatment and neoadjuvant or adjuvant chemotherapy significantly improves [invasive] DFS, [distant] DFS and OS with limited and manageable toxicity and without new safety signals,” Tutt summarized.
Describing germline BRCA1/2 testing as “an important companion diagnostic for adjuvant treatment decisions in breast cancer,” the presenter concluded that the US FDA has now approved olaparib for use in patients with these mutations and HER2-negative, high-risk early-stage breast cancer disease after neoadjuvant or adjuvant chemotherapy.
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