OS benefit of abemaciclib in HR-positive/HER2-negative advanced breast cancer not (yet) statistically significant

Results from the second interim analysis of the phase 3 MONARCH 3 showed that treatment with abemaciclib plus a non-steroidal aromatase inhibitor (NSAI) numerically increased overall survival (OS) in post-menopausal patients with HR-positive/HER2-negative advanced breast cancer compared with placebo plus NSAI in the first-line setting.

In the MONARCH 2 trial (NCT02107703), abemaciclib along with fulvestrant demonstrated significant OS benefit in pre- and post-menopausal patients with HR-positive/HER2-negative advanced breast cancer and disease progression on prior endocrine therapy [1]. The phase 3 MONARCH 3 trial (NCT02246621) investigated the efficacy of abemaciclib plus NSAI in the first-line setting in 493 post-menopausal patients with HR-positive/HER2-negative advanced breast cancer.

Previously, the MONARCH 3 trial already demonstrated a robust progression-free survival (PFS) benefit (HR 0.540; P<0.0001) of abemaciclib/NSAI versus placebo/NSAI, which led to a global regulatory approval of the treatment [2,3]. As per the gold standard for efficacy assessment, a demonstration of the OS benefit of abemaciclib/NSAI was requested by the EMA. Prof. Matthew Goetz (Mayo Clinic Rochester, MN, USA) presented the results of the pre-specified second interim OS analysis (data cut-off 2 July 2021), which was scheduled after ∼252 events in the intention-to-treat population (80% of planned events for final OS analysis) [4].

With 70.2 months of median follow-up, the median OS was 67.1 months for abemaciclib plus NSAI versus 54.5 months for placebo plus NSAI (HR 0.754; P=0.0301). This P-value is not statistically significant due to the pre-defined statistical analysis plan, because of multiple analyses of this endpoint, each with a specific statistical power. In the subgroup of patients with visceral disease (sVD; n=263) median OS was 65.1 months versus 48.8 months in the abemaciclib plus NSAI and placebo plus NSAI arms, respectively (HR 0.708; P=0.0392). This is again not statistically significant due to the statistical analysis plan.

Median chemotherapy-free survival in the intention-to-treat population favoured abemaciclib plus NSAI over placebo plus NSAI (46.7 vs 30.6 months; HR 0.636). No new safety concerns were observed after prolonged exposure to abemaciclib.

“In the second interim OS analysis from MONARCH 3, a numerically longer OS was observed in both the intention-to-treat and the sVD population with the addition of abemaciclib to NSAI,” summarised Prof. Goetz. “Neither met the threshold for formal statistical significance, but data are maturing favourably.” The final OS analysis is expected in 2023.

1. Sledge GW, et al. JAMA Oncol. 2020;6(1):116–124.
2. Goetz MP, et al. J Clin Oncol. 2017;35(32):3638–3646.
3. Johnston S, et al. NPJ Breast Cancer. 2019;5:5.
4. Goetz M, et al. MONARCH 3: Interim overall survival (OS) results of abemaciclib plus a nonsteroidal aromatase inhibitor (NSAI) in patients (pts) with HR+, HER2- advanced breast cancer (ABC). Abstract LBA15, ESMO Congress 2022, 09–13 September, Paris, France.

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Posted on 16 November, 202218 March, 2024