LBA17 Overall survival (OS) results from the phase III MONALEESA-2 (ML-2) trial of postmenopausal patients (pts) with hormone receptor positive/human epidermal growth factor receptor 2 negative (HR+/HER2−) advanced breast cancer (ABC) treated with endocrine therapy (ET) ± ribociclib (RIB)

Hortobágyi, G. N.; Stemmer, S. M.; Burris, HA; Yap, Yoon Sim; Sonke, Gabe S.; Hart, Lowell L.; Campone, M.; Petráková, Katarína; Winer, Eric P.; Janni, W; Conte, P.F.; Cameron, David; André, Fabrice; Arteaga, CL; Zarate, Juan Pablo; Chakravartty, Arunava; Taran, Tanya; Gac, Fabienne Le; Serra, Patrizia; O’Shaughnessy, Joyce

doi:10.1016/j.annonc.2021.08.2090

Cited by 64 publications

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“…Breast cancer that develops in premenopausal women may have biologic differences from that which develops in postmenopausal women [18]. According to recently updated OS data with ribociclib, we can compare OS of 41 months [3] in premenopausal women to 51 months [19] in postmenopausal patients treated with ET alone (control arm) in the MBC frontline setting. It can be expected that the premenopausal breast cancer biology would be more aggressive than postmenopausal one.…”

Section: Discussionmentioning

confidence: 99%

Exploratory analysis of biomarkers associated with clinical outcomes from the study of palbociclib plus endocrine therapy in premenopausal women with hormone receptor-positive, HER2-negative metastatic breast cancer

et al. 2022

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Background: Palbociclib plus endocrine therapy (ET) demonstrated significant progression-free survival (PFS) benefit in Young Pearl, a randomized phase ll trial comparing palbociclib þ ET versus capecitabine in premenopausal women with hormone receptor positive, HER2 negative metastatic breast cancer (MBC). This exploratory analysis investigated potential biomarkers of palbociclib plus ET on PFS. Patients and methods: Of 178 patients randomized (92 palbociclib plus ET; 86 capecitabine), we performed targeted sequencing (141 patients) and whole transcriptome sequencing (165 patients) using baseline tumor samples to examine genomic alteration in relation to drug response on PFS. Hazard ratios (HRs) were estimated using unstratified Cox proportional hazards models. Results: PIK3CA (41%) and TP53 (33%) mutations and CCND1 copy number variation (29%) were found most frequently in targeted sequencing of 141 patients. ESR1 mutations were found only in 3.5% of patients of this population. Luminal type showed better prognosis in palbociclib þ ET arm but no impact on PFS difference in capecitabine arm. High TMB, TP53 mutation, PTEN loss of function mutation and RB1 pathway alteration showed worse prognosis in palbociclib plus ET arm. Patients with BRCA2 pathogenic mutations showed worse prognosis regardless of PAM50 subtypes. AURKA mutation/amplification, BRIP1/ MYC/RAD51C amplification were significantly associated to the patients with short PFS <6 month. Conclusion: Of palbociclib plus ET, luminal type showed better prognosis and BRCA2 pathogenic mutation showed worse prognosis regardless luminal/non-luminal type. Further exploration of molecular variables is warranted to determine and validate biomarkers of efficacy and resistance.

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Section: Discussionmentioning

confidence: 99%

Exploratory analysis of biomarkers associated with clinical outcomes from the study of palbociclib plus endocrine therapy in premenopausal women with hormone receptor-positive, HER2-negative metastatic breast cancer

et al. 2022

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“…This difference was statistically significant. The therapeutic benefit was detectable across almost all subgroups, but in the analysis of de novo metastatic patients vs. patients after relapse a trend was noted, as the positive effect favouring ribociclib was mainly seen in the group of de novo patients [3].…”

Section: Introductionmentioning

confidence: 92%

Update Breast Cancer 2021 Part 5 – Advanced Breast Cancer

Lüftner

Schütz

Stickeler

et al. 2022

Geburtshilfe Frauenheilkd

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Despite the COVID 19 pandemic and mostly virtual congresses, innovation in the treatment of breast cancer patients continues at an unabated pace. This review summarises the current developments. Initial overall survival data for CDK4/6 inhibitor treatment in combination with an aromatase inhibitor as the first advanced line of therapy in treatment-naive postmenopausal patients have been published. Similarly, a trial comparing trastuzumab-deruxtecan versus trastuzumab-emtansine revealed a clear benefit regarding progression-free survival. Understanding of biomarkers making checkpoint inhibitor therapy particularly effective is increasing, and new compounds such as oral selective estrogen receptor destabilisers (SERDs) are entering clinical development and completing the first phase III trials.

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“…The last generation of CDK4/6 inhibitors (CDKi) includes palbociclib (PD 0332991), ribociclib (LEE011), and abemaciclib (LY2835219), which are currently approved for the treatment of advanced and/or metastatic hormone receptor-positive/HER2-neu-negative (HR+/HER2−) breast cancer in combination with hormonal therapy. These combinations have significantly improved clinical outcomes when compared to anti-estrogen monotherapy, as demonstrated by the randomized phase III trials PALOMA, MONALEESA, and MONARCH [ 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 ]. Although these drugs have reported comparable clinical benefits, there are unique differences in their substrate selectivity and pharmacodynamics [ 17 , 18 , 19 ] that could explain the varying differences observed in certain clinical settings.…”

Section: Introductionmentioning

confidence: 99%

Biological Effects of Cyclin-Dependent Kinase Inhibitors Ribociclib, Palbociclib and Abemaciclib on Breast Cancer Bone Microenvironment

Iuliani

Simonetti

Ribelli

et al. 2022

IJMS

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The CDK4/6 inhibitors (CDKi) palbociclib, ribociclib, and abemaciclib are currently approved in combination with anti-estrogen therapy for the treatment of advanced and/or metastatic hormone receptor-positive/HER2-neu-negative breast cancer patients. Given the high incidence of bone metastases in this population, we investigated and compared the potential effects of palbociclib, ribociclib, and abemaciclib on the breast cancer bone microenvironment. Primary osteoclasts (OCs) and osteoblasts (OBs) were obtained from human monocyte and mesenchymal stem cells, respectively. OC function was evaluated by tartrate-resistant acid phosphatase assay and real-time PCR; OB activity was assessed by an alizarin red assay. OB/breast cancer co-culture models were generated via the seeding of MCF-7 cells on a layer of OBs, and tumor cell proliferation was analyzed using flow cytometry. Here, we showed that ribociclib, palbociclib, and abemaciclib exerted similar inhibitory effects on the OC differentiation and expression of bone resorption markers without affecting OC viability. On the other hand, the three CDKi did not affect the ability of OB to produce bone matrix, even if the higher doses of palbociclib and abemaciclib reduced the OB viability. In OB/MCF-7 co-culture models, palbociclib demonstrated a lower anti-tumor effect than ribociclib and abemaciclib. Overall, our results revealed the direct effects of CDKi on the tumor bone microenvironment, highlighting differences potentially relevant for clinical practice.

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LBA17 Overall survival (OS) results from the phase III MONALEESA-2 (ML-2) trial of postmenopausal patients (pts) with hormone receptor positive/human epidermal growth factor receptor 2 negative (HR+/HER2−) advanced breast cancer (ABC) treated with endocrine therapy (ET) ± ribociclib (RIB)

Abstract: LBA17Overall survival (OS) results from the phase III MONALEESA-2 (ML-2) trial of postmenopausal patients (pts) with hormone receptor positive/human epidermal growth factor receptor 2 negative (HR+/HER2L) advanced breast cancer (ABC) treated with endocrine therapy (ET) ± ribociclib (RIB)

Cited by 64 publications

References 0 publications

Exploratory analysis of biomarkers associated with clinical outcomes from the study of palbociclib plus endocrine therapy in premenopausal women with hormone receptor-positive, HER2-negative metastatic breast cancer

Exploratory analysis of biomarkers associated with clinical outcomes from the study of palbociclib plus endocrine therapy in premenopausal women with hormone receptor-positive, HER2-negative metastatic breast cancer

Update Breast Cancer 2021 Part 5 – Advanced Breast Cancer

Biological Effects of Cyclin-Dependent Kinase Inhibitors Ribociclib, Palbociclib and Abemaciclib on Breast Cancer Bone Microenvironment

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