Circulating Biomarkers of CDK4/6 Inhibitors Response in Hormone Receptor Positive and HER2 Negative Breast Cancer
Abstract
:Simple Summary
Abstract
1. Introduction
2. Biomarkers of Resistance to CDK4/6i on ctDNA
2.1. Biomarkers of De Novo CDK4/6i Resistance on ctDNA
2.2. Dynamics of ctDNA Biomarkers
2.3. Circulating Biomarkers of Acquired Resistance on ctDNA
3. The Role of Thymidine Kinase-1 Serum Activity
4. Additional Circulating Biomarkers
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Name | Phase | Setting | Treatments | Results |
---|---|---|---|---|
PALOMA-3 [4] | 3 | MBC II line | Pal and Ful vs. Plb and Ful | 9.2 vs. 3.8 months PFS HR 0.42, 95% CI 0.32–0.56 |
NEOPALANA [20] | 2 | Neoadjuvant | Ana → Ana and Pal → Ana | 87% vs. 26% CCCA |
TREND [21] | 2 | MBC ≥ II line | Pal vs. Pal and ET earlier line | 60% vs. 54% CBR |
PEARL [22] | 3 | MBC (AI-resistant) | Cohort 1: Pal and Exe vs. Cap Cohort 2: Pal and Ful vs. Cap | Cohort 2: 7.5 vs. 10.0 months PFS HR 1.13, 95% CI 0.85–1.50 Cohorts 1 + 2, ESR1 wt: 8.0 vs. 10.6 months PFS HR: 1.11, 95% CI: 0.87–1.41 |
MONARCH-2 [9] | 3 | MBC II line | Abema and Ful vs. Plb + Ful | 16.4 vs. 9.3 months PFS HR 0.553, 95% CI 0.449–0.681 |
MONALEESA-2 [6] | 3 | MBC I line | Ribo and Let vs. Plb and Let | NR vs. 14.7 months PFS HR 0.56, 95% CI 0.43–0.72 |
MONALEESA-3 [10] | 3 | MBC I-II line | Ribo and Ful vs. Plb and Ful | 20.5 vs. 12.8 months PFS HR 0.593, 95% CI 0.480–0.732 |
MONALEESA-7 [11] | 3 | MBC I line | Ribo and Tam or NSAI and Gos vs. Plb and Tam or NSAI and Gos | 23.8 vs. 13.0 months PFS HR 0.55, 95% CI 0.44–0.69 |
Clinical trial | Correlative Studies | Methods | Main Circulating Biomarkers |
---|---|---|---|
PALOMA-3 [4] | O’Leary et al. [23] | Targeted panel | TP53, FGFR1, TF |
Cristofanilli et al. [24] | ddPCR | PIK3CA | |
Fribbens et al. [25] | ddPCR | ESR1 | |
O’Leary et al. [26] | ddPCR | PIK3CA, ESR1 dynamics | |
O’Leary et al. [27] | Targeted panel | acquired mutations | |
NEOPALANA [20] | Bagegni et al. [28] | Divitum | TKa |
TREND [21] | McCartney et al. [29] | Divitum | TKa |
Galardi et al. [30] | CellSearch | CTC | |
MONARCH-2 [9] | Tolaney et al. [31] | ddPCR | PIK3CA, ESR1 |
MONALEESA-2 [6] | Andre et al. [32] | Targeted panel | CHD4, ATM, FRS2, PRKCA, CDKN2A/2B/2C, AKT1 |
Hortobagyi et al. [33] | Targeted panel | PIK3CA, TP53, RTK | |
MONALEESA-3 [10] | Andre et al. [32] | Targeted panel | CHD4, ATM, FRS2, PRKCA, CDKN2A/2B/2C, AKT1 |
Neven et al. [34] | Targeted panel | PIK3CA, ESR1, TP53, FGFR1, CC, RTK | |
MONALEESA-7 [11] | Andre et al. [32] | Targeted panel | CHD4, ATM, FRS2, PRKCA, CDKN2A/2B/2C, AKT1 |
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Migliaccio, I.; Leo, A.; Galardi, F.; Guarducci, C.; Fusco, G.M.; Benelli, M.; Di Leo, A.; Biganzoli, L.; Malorni, L. Circulating Biomarkers of CDK4/6 Inhibitors Response in Hormone Receptor Positive and HER2 Negative Breast Cancer. Cancers 2021, 13, 2640. https://doi.org/10.3390/cancers13112640
Migliaccio I, Leo A, Galardi F, Guarducci C, Fusco GM, Benelli M, Di Leo A, Biganzoli L, Malorni L. Circulating Biomarkers of CDK4/6 Inhibitors Response in Hormone Receptor Positive and HER2 Negative Breast Cancer. Cancers. 2021; 13(11):2640. https://doi.org/10.3390/cancers13112640
Chicago/Turabian StyleMigliaccio, Ilenia, Angela Leo, Francesca Galardi, Cristina Guarducci, Giulio Maria Fusco, Matteo Benelli, Angelo Di Leo, Laura Biganzoli, and Luca Malorni. 2021. "Circulating Biomarkers of CDK4/6 Inhibitors Response in Hormone Receptor Positive and HER2 Negative Breast Cancer" Cancers 13, no. 11: 2640. https://doi.org/10.3390/cancers13112640