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 . 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) .
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.
- Sledge GW, et al. JAMA Oncol. 2020;6(1):116–124.
- Goetz MP, et al. J Clin Oncol. 2017;35(32):3638–3646.
- Johnston S, et al. NPJ Breast Cancer. 2019;5:5.
- 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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Table of Contents: ESMO 2022
Letter from the Editor
High pathological responses to neoadjuvant immune checkpoint inhibition in locally advanced dMMR colon cancer
Fruquintinib: a potential new treatment for patients with refractory mCRC
Second-line avelumab is effective in patients with MSI-H/dMMR mCRC
Upper Gastrointestinal Cancer
Deep learning models predict the risk of relapse and the mutational profile in GIST
Addition of pembrolizumab to lenvatinib does not improve OS in advanced HCC
New, highly selective inhibitor of FGFR2 driver alterations and resistance mutations
Chemo-immunotherapy in gastric cancer is more effective when administered in parallel
Tumour infiltrating lymphocytes identify patients with immunogenic triple-negative breast cancer
OS benefit of abemaciclib in HR-positive/HER2-negative advanced breast cancer not (yet) statistically significant
OS benefit of sacituzumab govitecan in pre-treated HR-positive/HER2-negative metastatic breast cancer
A pathway from air pollution to lung cancer in non-smokers identified
Selective KRASG12C inhibitor sotorasib demonstrates superior PFS and ORR compared to docetaxel in previously treated patients with NSCLC
Promising clinical activity of tepotinib plus osimertinib in NSCLC with MET amplification after progression on first-line osimertinib
High pathological responses in borderline resectable NSCLC patients after induction with dual immunotherapy and concurrent chemoradiotherapy
Treatment with tumour-infiltrating lymphocytes for advanced melanoma outperforms ipilimumab
Neoadjuvant pembrolizumab outperforms adjuvant pembrolizumab in resectable stage III–IV melanomas
Survival-benefit of neoadjuvant T-VEC maintained over 5 years of follow-up
Baseline ctDNA predicts survival in resected stage III–IV melanoma
Genitourinary Cancer – Prostate Cancer
Overall survival benefit of abiraterone in mHSPC is maintained for 7 years
Limited benefit of adding long-term ADT to post-operative radiotherapy in prostate cancer
Intensified ADT benefits biochemical progression-free survival in biochemically relapsed prostate cancer
Genitourinary Cancer – Non-Prostate Cancer
Adjuvant nivolumab plus ipilimumab does not improve survival in patients with localised RCC at high risk of relapse after nephrectomy
Triple therapy improves progression-free survival in patients with advanced RCC versus dual therapy
Adjuvant atezolizumab does not improve outcomes for patients with RCC and increased risk of recurrence
OS benefit for advanced ovarian cancer patients treated with maintenance olaparib
Maintenance tegafur-uracil does not improve survival in locally advanced cervical cancer
Head and Neck Cancer
Adding first-line pembrolizumab to CRT in locally advanced HNSCC does not significantly prolong survival or event-free survival
5-FU-free chemotherapy combination as an alternative for first-line treatment of recurrent or metastatic HNSCC
Epstein Barr virus-specific autologous cytotoxic T lymphocytes do not improve survival in nasopharyngeal carcinoma