Experts present data
Contributing to the growing body of evidence for KISQALI
Overall survival (OS) in patients (pts) with advanced breast cancer (ABC) with visceral metastases (mets), including those with liver mets, treated with ribociclib (RIB) plus endocrine therapy (ET) in the MONALEESA (ML)-3 and -7 trials.
Yardley DA, Nusch A, Yap Y-S, et al.
Summary
- A subanalysis of the MONALEESA-3 and MONALEESA-7 clinical trials evaluated overall survival in patients with visceral metastases
- There was a focus on those with liver metastases, whose prognosis is especially poor
- Overall survival benefit with KISQALI + ET vs control arm in patients with visceral metastases was consistent with that seen in the ITT populations of both trials
- A substantial overall survival benefit vs control arm was seen in patients with liver metastases
Denise A. Yardley, MD, shares highlights
Study design
- In MONALEESA-3, postmenopausal patients received KISQALI + fulvestrant or placebo + fulvestrant as 1L or 2L treatment
- In MONALEESA-7, premenopausal patients received KISQALI + ET or placebo + ET
Broad analysis reveals potential biomarkers of response or resistance to KISQALI2
Pooled ctDNA analysis of the MONALEESA (ML) phase III advanced breast cancer (ABC) trials.
André F, Su F, Solovieff N, et al.
Summary
- The largest biomarker analysis of any CDK4/6 inhibitor in aBC leveraged data from patients across the 3 KISQALI MONALEESA trials
- This analysis identified several potential markers of response and resistance to KISQALI
- Response: FRS2, PRKCA, MDM2, ERBB2, AKT1, and BRCA1/2
- Resistance: CHD4, BCL11B, ATM, or CDKN2A/2B/2C
Fabrice André, MD, shares highlights
Analysis Methods
- Baseline ctDNA from 1503 patients enrolled in MONALEESA-2, MONALEESA-3, and MONALEESA-7 was assessed using NGS with a targeted panel of 557 genes
- Genes with an alteration frequency of ≥2% seen in ≥15 patients per treatment arm were included, for a total of 83 genes
- A genetic alteration was defined as the presence of mutation, short insertion/deletion, or copy number alteration
- Cox proportional hazard model of PFS was fit with gene-by-treatment interaction
- Genes with interaction P<0.10 and genes of interest were investigated
Results
- A trend for increased PFS benefit with KISQALI vs the control arm was seen among patients with alterations in:
- FRS2 and PRKCA (treatment interaction P<0.05)
- MDM2, ERBB2, AKT1, and BRCA1/2 (P>0.05 but considered actionable)
- Little or no added PFS benefit with KISQALI vs the control arm was seen among patients with alterations in:
- CHD4, BCL11B, ATM, or CDKN2A/2B/2C (P interaction <0.10; HR>0.80)
CompLEEment-1 findings add to the body of evidence for KISQALI3
Updated results from the phase IIIb CompLEEment-1 study of ribociclib (RIB) plus letrozole (LET) in the treatment of HR+, HER2– advanced breast cancer (ABC).
De Laurentiis M, Borštnar S, Campone M, et al.
Summary
- This analysis confirmed the safety and efficacy of KISQALI + letrozole in a large, diverse cohort of patients with HR+/HER2– aBC that closely resembled real-world clinical practice (N=3246)
- Safety and efficacy data were consistent with findings from the MONALEESA trials
- CompLEEment-1 was the largest CDK4/6 inhibitor trial in aBC to date
Michelino De Laurentiis, MD, shares highlights
Study design
- Patients with HR+/HER2– aBC, ≤1 line of prior chemotherapy, and no prior ET for aBC were enrolled
- This diverse population included premenopausal and postmenopausal women, patients with an ECOG PS of 2, and patients who had stable CNS lesions
- 1.2% (n=39) of patients were male
- The primary end points were safety and tolerability
Results
Patient disposition:
- 3246 patients received ≥1 dose of KISQALI
- The median duration of follow-up was 25.4 months
- The median treatment exposure was 17.8 months
