Cyclin-dependent kinase 4 and 6 inhibitors for hormone receptor-positive breast cancer: past, present, and future

Finn, 2016, Palbociclib and letrozole in advanced breast cancer, N Engl J Med, 375, 1925, 10.1056/NEJMoa1607303 Hortobagyi, 2016, Ribociclib as first-line therapy for HR-positive, advanced breast cancer, N Engl J Med, 375, 1738, 10.1056/NEJMoa1609709 Goetz, 2017, MONARCH 3: abemaciclib as initial therapy for advanced breast cancer, J Clin Oncol, 35, 3638, 10.1200/JCO.2017.75.6155 Turner, 2015, Palbociclib in hormone-receptor-positive advanced breast cancer, N Engl J Med, 373, 209, 10.1056/NEJMoa1505270 Turner, 2018, Overall survival with palbociclib and fulvestrant in advanced breast cancer, N Engl J Med, 379, 1926, 10.1056/NEJMoa1810527 Sledge, 2017, MONARCH 2: abemaciclib in combination with fulvestrant in women with HR+/HER2- advanced Breast cancer who had progressed while receiving endocrine therapy, J Clin Oncol, 35, 2875, 10.1200/JCO.2017.73.7585 Sledge, 2019, The effect of abemaciclib plus fulvestrant on overall survival in hormone receptor-positive, ERBB2-negative breast cancer that progressed on endocrine therapy-MONARCH 2: a randomized clinical trial, JAMA Oncol, 6, 116, 10.1001/jamaoncol.2019.4782 Slamon, 2018, Phase III randomized study of ribociclib and fulvestrant in hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer: MONALEESA-3, J Clin Oncol, 36, 2465, 10.1200/JCO.2018.78.9909 Slamon, 2019, Overall survival with ribociclib plus fulvestrant in advanced breast cancer, N Engl J Med Tripathy, 2018, Ribociclib plus endocrine therapy for premenopausal women with hormone-receptor-positive, advanced breast cancer (MONALEESA-7): a randomised phase 3 trial, Lancet Oncol, 19, 904, 10.1016/S1470-2045(18)30292-4 Im, 2019, Overall survival with ribociclib plus endocrine therapy in breast cancer, N Engl J Med, 381, 307, 10.1056/NEJMoa1903765 Weinberg, 1995, The retinoblastoma protein and cell cycle control, Cell, 81, 323, 10.1016/0092-8674(95)90385-2 Wang, 1994, The retinoblastoma tumor suppressor protein, Adv Cancer Res, 64, 25, 10.1016/S0065-230X(08)60834-9 Fry, 2004, Specific inhibition of cyclin-dependent kinase 4/6 by PD 0332991 and associated antitumor activity in human tumor xenografts, Mol Cancer Ther, 3, 1427, 10.1158/1535-7163.1427.3.11 Millar, 2009, Cyclin D1b protein expression in breast cancer is independent of cyclin D1a and associated with poor disease outcome, Oncogene, 28, 1812, 10.1038/onc.2009.13 Arnold, 2005, Cyclin D1 in breast cancer pathogenesis, J Clin Oncol, 23, 4215, 10.1200/JCO.2005.05.064 Bosco, 2007, RB in breast cancer: at the crossroads of tumorigenesis and treatment, Cell Cycle, 6, 667, 10.4161/cc.6.6.3988 Treré, 2009, High prevalence of retinoblastoma protein loss in triple-negative breast cancers and its association with a good prognosis in patients treated with adjuvant chemotherapy, Ann Oncol, 20, 1818, 10.1093/annonc/mdp209 Arima, 2008, Rb depletion results in deregulation of E-cadherin and induction of cellular phenotypic changes that are characteristic of the epithelial-to-mesenchymal transition, Cancer Res, 68, 5104, 10.1158/0008-5472.CAN-07-5680 Butt, 2005, Downstream targets of growth factor and oestrogen signalling and endocrine resistance: the potential roles of c-Myc, cyclin D1 and cyclin E, Endocr Relat Cancer, 12, S47, 10.1677/erc.1.00993 Musgrove, 1994, Cyclin D1 induction in breast cancer cells shortens G1 and is sufficient for cells arrested in G1 to complete the cell cycle, Proc Natl Acad Sci USA, 91, 8022, 10.1073/pnas.91.17.8022 Nair, 2008, Regulation of hormonal therapy resistance by cell cycle machinery, Gene Ther Mol Biol, 12, 395 Thangavel, 2011, Therapeutically activating RB: reestablishing cell cycle control in endocrine therapy-resistant breast cancer, Endocr Relat Cancer, 18, 333, 10.1530/ERC-10-0262 Altucci, 1997, Estrogen induces early and timed activation of cyclin-dependent kinases 4, 5, and 6 and increases cyclin messenger ribonucleic acid expression in rat uterus, Endocrinology, 138, 978, 10.1210/endo.138.3.5002 Geum, 1997, Estrogen-induced cyclin D1 and D3 gene expressions during mouse uterine cell proliferation in vivo: differential induction mechanism of cyclin D1 and D3, Mol Reprod Dev, 46, 450, 10.1002/(SICI)1098-2795(199704)46:4<450::AID-MRD2>3.0.CO;2-N Roberts, 2012, Multiple roles of cyclin-dependent kinase 4/6 inhibitors in cancer therapy, J Natl Cancer Inst, 104, 476, 10.1093/jnci/djs002 Yu, 2001, Specific protection against breast cancers by cyclin D1 ablation, Nature, 411, 1017, 10.1038/35082500 Yu, 2006, Requirement for CDK4 kinase function in breast cancer, Cancer Cell, 9, 23, 10.1016/j.ccr.2005.12.012 Toogood, 2005, Discovery of a potent and selective inhibitor of cyclin-dependent kinase 4/6, J Med Chem, 48, 2388, 10.1021/jm049354h Finn, 2009, PD 0332991, a selective cyclin D kinase 4/6 inhibitor, preferentially inhibits proliferation of luminal estrogen receptor-positive human breast cancer cell lines in vitro, Breast Cancer Res, 11, R77, 10.1186/bcr2419 Finn, 2015, The cyclin-dependent kinase 4/6 inhibitor palbociclib in combination with letrozole versus letrozole alone as first-line treatment of oestrogen receptor-positive, HER2-negative, advanced breast cancer (PALOMA-1/TRIO-18): a randomised phase 2 study, Lancet Oncol, 16, 25, 10.1016/S1470-2045(14)71159-3 Gelbert, 2014, Preclinical characterization of the CDK4/6 inhibitor LY2835219: in-vivo cell cycle-dependent/independent anti-tumor activities alone/in combination with gemcitabine, Invest New Drugs, 32, 825, 10.1007/s10637-014-0120-7 Rader, 2013, Dual CDK4/CDK6 inhibition induces cell-cycle arrest and senescence in neuroblastoma, Clin Cancer Res, 19, 6173, 10.1158/1078-0432.CCR-13-1675 Dickson, 2014, Molecular pathways: CDK4 inhibitors for cancer therapy, Clin Cancer Res, 20, 3379, 10.1158/1078-0432.CCR-13-1551 Zhang, 2014, Antiproliferative effects of CDK4/6 inhibition in CDK4-amplified human liposarcoma in vitro and in vivo, Mol Cancer Ther, 13, 2184, 10.1158/1535-7163.MCT-14-0387 Tate, 2014, Semi-mechanistic pharmacokinetic/pharmacodynamic modeling of the antitumor activity of LY2835219, a new cyclin-dependent kinase 4/6 inhibitor, in mice bearing human tumor xenografts, Clin Cancer Res, 20, 3763, 10.1158/1078-0432.CCR-13-2846 Asghar, 2015, The history and future of targeting cyclin-dependent kinases in cancer therapy, Nat Rev Drug Discov, 14, 130, 10.1038/nrd4504 Dean, 2010, Therapeutic CDK4/6 inhibition in breast cancer: key mechanisms of response and failure, Oncogene, 29, 4018, 10.1038/onc.2010.154 Malumbres, 2004, Mammalian cells cycle without the D-type cyclin-dependent kinases Cdk4 and Cdk6, Cell, 118, 493, 10.1016/j.cell.2004.08.002 Cristofanilli, 2016, Lancet Oncol, 17, 425, 10.1016/S1470-2045(15)00613-0 Park, 2019, A randomized phase II study of palbociclib plus exemestane with GNRH agonist versus capecitabine in premenopausal women with hormone receptor-positive metastatic breast cancer (KCSG-BR 15-10, NCT02592746), J Clin Oncol, 37, 10.1200/JCO.2019.37.15_suppl.1007 Dickler, 2017, MONARCH 1, a phase II study of abemaciclib, a CDK4 and CDK6 inhibitor, as a single agent, in patients with refractory HR+/HER2– metastatic breast cancer, Clin Cancer Res, 23, 5218, 10.1158/1078-0432.CCR-17-0754 Wander, 2019, A multicenter analysis of abemaciclib after progression on palbociclib in patients (pts) with hormone receptor-positive (HR+)/HER2- metastatic breast cancer (MBC), J Clin Oncol, 37, 10.1200/JCO.2019.37.15_suppl.1057 dos Anjos, 2019, A large retrospective analysis of CDK 4/6 inhibitor retreatment in ER+ metastatic breast cancer (MBC), J Clin Oncol, 37, 10.1200/JCO.2019.37.15_suppl.1053 Spring, 2017, Clinical management of potential toxicities and drug interactions related to cyclin-dependent kinase 4/6 inhibitors in breast cancer: practical considerations and recommendations, Oncologist, 22, 1039, 10.1634/theoncologist.2017-0142 Kim, 2013, Abstract PR02: LEE011: an orally bioavailable, selective small molecule inhibitor of CDK4/6– reactivating Rb in cancer, Mol Cancer Ther, 12 Brufsky, 2017, Long-term management of patients with hormone receptor-positive metastatic breast cancer: Concepts for sequential and combination endocrine-based therapies, Cancer Treat Rev, 59, 22, 10.1016/j.ctrv.2017.06.004 Singh, 2018, A U.S. Food and Drug Administration pooled analysis of outcomes of older women with hormone-receptor positive metastatic breast cancer treated with a CDK4/6 inhibitor as initial endocrine based therapy, Cancer Res, 78, GS05 Baselga, 2012, Everolimus in postmenopausal hormone-receptor-positive advanced breast cancer, N Engl J Med, 366, 520, 10.1056/NEJMoa1109653 André, 2019, Alpelisib for PIK3CA-mutated, hormone receptor-positive advanced breast cancer, N Engl J Med, 380, 1929, 10.1056/NEJMoa1813904 Costa, 2020, PTEN loss mediates clinical cross-resistance to CDK4/6 and PI3Kα inhibitors in breast cancer, Cancer Discov, 10, 72, 10.1158/2159-8290.CD-18-0830 Drago, 2019, FGFR1 gene amplification mediates endocrine resistance but retains TORC sensitivity in metastatic hormone receptor positive (HR+) breast cancer, Clin Cancer Res, 25, 6443, 10.1158/1078-0432.CCR-19-0138 Herrera-Abreu, 2016, Early adaptation and acquired resistance to CDK4/6 inhibition in estrogen receptor-positive breast cancer, Cancer Res, 76, 2301, 10.1158/0008-5472.CAN-15-0728 Condorelli, 2018, Polyclonal RB1 mutations and acquired resistance to CDK 4/6 inhibitors in patients with metastatic breast cancer, Ann Oncol, 29, 640, 10.1093/annonc/mdx784 O'Leary, 2018, The genetic landscape and clonal evolution of breast cancer resistance to palbociclib plus fulvestrant in the PALOMA-3 Trial, Cancer Discov, 8, 1390, 10.1158/2159-8290.CD-18-0264 Bertucci, 2019, Genomic characterization of metastatic breast cancers, Nature, 569, 560, 10.1038/s41586-019-1056-z Caldon, 2012, Cyclin E2 overexpression is associated with endocrine resistance but not insensitivity to CDK2 inhibition in human breast cancer cells, Mol Cancer Ther, 11, 1488, 10.1158/1535-7163.MCT-11-0963 Turner, 2019, Cyclin E1 expression and palbociclib efficacy in previously treated hormone receptor-positive metastatic breast cancer, J Clin Oncol, 37, 1169, 10.1200/JCO.18.00925 Yang, 2017, Acquired CDK6 amplification promotes breast cancer resistance to CDK4/6 inhibitors and loss of ER signaling and dependence, Oncogene, 36, 2255, 10.1038/onc.2016.379 Cornell, 2019, MicroRNA-mediated suppression of the TGF-β pathway confers transmissible and reversible CDK4/6 inhibitor resistance, Cell Rep, 26, 2667, 10.1016/j.celrep.2019.02.023 Wander, 2018, Whole exome sequencing (WES) in hormone-receptor positive (HR+) metastatic breast cancer (MBC) to identify mediators of resistance to cyclin-dependent kinase 4/6 inhibitors (CDK4/6i), Proc Am Soc Clin Oncol, 36 Nayar, 2019, Acquired HER2 mutations in ER+ metastatic breast cancer confer resistance to estrogen receptor-directed therapies, Nat Genet, 51, 207, 10.1038/s41588-018-0287-5 Medford, 2019, Blood-based monitoring identifies acquired and targetable driver HER2 mutations in endocrine-resistant metastatic breast cancer, NPJ Precis Oncol, 3, 18, 10.1038/s41698-019-0090-5 Mao, 2018, Abstract PD4-01: The role of FGF/FGFR axis in resistance to SERDs and CDK4/6 inhibitors in ER+ breast cancer, Cancer Res, 78, PD4 Formisano, 2019, Aberrant FGFR signaling mediates resistance to CDK4/6 inhibitors in ER+ breast cancer, Nat Commun, 10, 10.1038/s41467-019-09068-2 Li, 2018, Loss of the FAT1 tumor suppressor promotes resistance to CDK4/6 inhibitors via the Hippo pathway, Cancer Cell, 34, 893, 10.1016/j.ccell.2018.11.006 Olson, 2019, Development of a selective CDK7 covalent inhibitor reveals predominant cell-cycle phenotype, Cell Chem Biol, 26, 792, 10.1016/j.chembiol.2019.02.012 Goel, 2017, CDK4/6 inhibition triggers anti-tumour immunity, Nature, 548, 471, 10.1038/nature23465 Pan, 2017, 20-year risks of breast-cancer recurrence after stopping endocrine therapy at 5 years, N Engl J Med, 377, 1836, 10.1056/NEJMoa1701830 Ma, 2017, NeoPalAna: neoadjuvant palbociclib, a cyclin-dependent kinase 4/6 inhibitor, and anastrozole for clinical stage 2 or 3 estrogen receptor-positive breast cancer, Clin Cancer Res, 23, 4055, 10.1158/1078-0432.CCR-16-3206 Martin M, Hurvitz SA, Chan D, et al. Final results of NeoMONARCH: a phase 2 neoadjuvant study of abemaciclib in postmenopausal women with hormone receptor positive (HR+), HER2 negative breast cancer (BC). 2017 San Antonio Breast Cancer Symposium; San Antonio, Texas, USA Dec 5–9, 2017 (abstr PD5-01). Johnston, 2019, Randomized phase II study evaluating palbociclib in addition to letrozole as neoadjuvant therapy in estrogen receptor-positive early breast cancer: PALLET trial, J Clin Oncol, 37, 178, 10.1200/JCO.18.01624 Cottu, 2018, Letrozole and palbociclib versus chemotherapy as neoadjuvant therapy of high-risk luminal breast cancer, Ann Oncol, 29, 2334, 10.1093/annonc/mdy448 Prat, 2020, Ribociclib plus letrozole versus chemotherapy for postmenopausal women with hormone receptor-positive, HER2-negative, luminal B breast cancer (CORALLEEN): an open-label, multicentre, randomised, phase 2 trial, Lancet Oncol, 21, 33, 10.1016/S1470-2045(19)30786-7 Arnedos, 2018, Modulation of Rb phosphorylation and antiproliferative response to palbociclib: the preoperative-palbociclib (POP) randomized clinical trial, Ann Oncol, 29, 1755, 10.1093/annonc/mdy202 Bardia, 2019, Triplet therapy (continuous ribociclib, everolimus, exemestane) in HR+/HER2− advanced breast cancer postprogression on a CDK4/6 inhibitor (TRINITI-1): efficacy, safety, and biomarker results, J Clin Oncol, 37, 10.1200/JCO.2019.37.15_suppl.1016 Tolaney, 2019, LBA23MonarcHER: a randomized phase II study of abemaciclib plus trastuzumab with or without fulvestrant versus trastuzumab plus standard-of-care chemotherapy in women with HR+, HER2+ advanced breast cancer (ABC), Ann Oncol, 30, v861, 10.1093/annonc/mdz394.012 Matutino, 2018, CDK4/6 inhibitors in breast cancer: beyond hormone receptor-positive HER2-negative disease, Ther Adv Med Oncol, 10, 10.1177/1758835918818346 Tan, 2019, Trilaciclib plus chemotherapy versus chemotherapy alone in patients with metastatic triple-negative breast cancer: a multicentre, randomised, open-label, phase 2 trial, Lancet Oncol, 20, 1587, 10.1016/S1470-2045(19)30616-3 Gao, 2019, CDK 4/6 inhibitor treatment for patients with hormone receptor-positive, HER2-negative, advanced or metastatic breast cancer: a US Food and Drug Administration pooled analysis, Lancet Oncol