7 oktober 2023: Bron: Annals of Oncology, Published:September 04, 2023
Resultaten van analyses van DNA van in bloed circulerend tumorweefsel = ctDNA bij patiënten met HR+/HER2- gevorderde uitgezaaide borstkanker die in de MONALEESA studies zijn behandeld met Ribociclib plus endocriene therapie / hormoontherapie laat zien dat bepaalde genmutaties een positief effect hebben op de behandeling en andere genmutaties een negatief effect op het uiteindelijke resultaat van de behandeling met CDK4/6 remmers.
Mutaties in ERBB2, FAT3, FRS2, MDM2, SFRP1 en ZNF217 gingen gepaard met grotere progressievrije overlevingstijd geassocieerd met de toevoeging van ribociclib aan ET.
Een hoge tumormutatielast en mutaties in ANO1, CDKN2A/2B/2C en RB1 gingen gepaard met minder gevoeligheid voor ribociclib plus ET.
Zie onderstaande grafieken:
Figure 2 PFS in patients with gene alterations associated with improved outcomes with RIB.
De resultaten uit deze studie is niet meer zo belangrijk voor de patiënten die al een behandeling kregen of nog krijgen met CDK4/6 remmers maar is natuurlijk wel belangrijk voor nieuwe patiënten met deze vorm van borstkanker. En toont weer maar eens het belang van een analyse van DNA van in bloed circulerend tumorweefsel = ctDNA die naar mijn mening bij elke vorm van gevorderde en dus vaak uitgezaaide kanker met solide tumoren zou moeten worden uitgevoerd. Of vooraf of na 1 maand na de start van een behandeling.
Het volledige studierapport is gratis in te zien of te downloaden. Klik op de titel van het abstract:
Pooled ctDNA analysis of MONALEESA phase III advanced breast cancer trials
Highlights
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We report an exploratory analysis of the association of gene alteration status and PFS across MONALEESA-2, -3, and -7.
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This analysis used the largest pooled biomarker dataset of the CDK4/6 inhibitor ribociclib in ABC to date.
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ERBB2, FAT3, FRS2, MDM2, SFRP1, and ZNF217 alterations were associated with increased sensitivity to ribociclib.
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ANO1, CDKN2A/2B/2C, and RB1 alterations and high TMB were associated with decreased sensitivity to ribociclib.
Background
The phase III MONALEESA trials tested the efficacy and safety of the cyclin-dependent kinase (CDK)4/6 inhibitor ribociclib with different endocrine therapy partners as first- or second-line treatment of hormone receptor–positive/human epidermal growth factor receptor 2–negative advanced breast cancer (ABC). Using the largest pooled biomarker dataset of the CDK4/6 inhibitor ribociclib in ABC to date, we identified potential biomarkers of response to ribociclib.
Patients and methods
Baseline circulating tumour DNA from patients in the MONALEESA trials was assessed using next-generation sequencing. An analysis of correlation between gene alteration status and progression-free survival (PFS) was carried out to identify potential biomarkers of response to ribociclib.
Results
Multiple frequently altered genes were identified. Alterations in ERBB2, FAT3, FRS2, MDM2, SFRP1, and ZNF217 were associated with a greater PFS benefit with ribociclib versus placebo. Patients with high tumour mutational burden (TMB) and with ANO1, CDKN2A/2B/2C, and RB1 alterations exhibited decreased sensitivity to ribociclib versus placebo.
Conclusions
Although exploratory, these results provide insight into alterations associated with the improved response to ribociclib treatment and may inform treatment sequencing in patients with actionable alterations following progression on CDK4/6 inhibitors. Validation of potential biomarkers identified here and development of prospective trials testing their clinical utility are warranted.
ClinicalTrials.gov identifiers
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Article info
Publication history
Published online: September 04, 2023
Publication stage
In Press Journal Pre-ProofIdentification
Copyright
© 2023 The Authors. Published by Elsevier Ltd on behalf of European Society for Medical Oncology.
User license
Creative Commons Attribution – NonCommercial – NoDerivs (CC BY-NC-ND 4.0) |
ScienceDirect
Access this article on ScienceDirectFigures
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Figure 1Oncoprint of genes altered in ≥3% of patients and genes of interest. -
Figure 2PFS in patients with gene alterations associated with improved outcomes with RIB.
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Figure 2PFS in patients with gene alterations associated with improved outcomes with RIB. -
Figure 3PFS in patients with gene alterations associated with decreased RIB activity. -
Figure 4Prognostic and predictive relationship between PFS and TMB. -
Figure 4Prognostic and predictive relationship between PFS and TMB. -
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