An address on normal schools of agriculture for Farmers' institute workers delivered... before the Pa. farmers' normal institute, held at Bellefonte, Pa., Oct. 11-14, 1904

Hamilton, J. Roland; Hamilton, John

doi:10.5962/bhl.title.21526

Cited by 1 publication

(2 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…One explanation for rapid progression on 2L endocrine monotherapy after palbociclib progression is pantumor cell release from G 1 /S blockade increasing proliferation following discontinuation of the CDK4/6i. Of note, this phenomenon was not observed in a pooled analysis of postprogression treatments after 1L ribociclib in the MONALEESA-2, MONALEESA-3, and MONALEESA-7 studies, wherein the mPFS for single-agent ET following progression on ribociclib was 8 months . In summary, these data suggest that improvements in PFS achieved while on palbociclib are not maintained during subsequent therapies, and this may contribute to the lack of an OS benefit.…”

Section: Endocrine Sensitivity After Cdk4/6imentioning

confidence: 79%

“…Determining optimal sequencing of CDK4/6i is critical, as recent data suggest loss of endocrine sensitivity following progression on CDK4/6i, with PFS of 2 to 3 months and response rates less than 5% . Most patients received prior palbociclib, and preliminary data from the pooled 2L data from MONALEESA-2, MONALEESA-3, and MONALEESA-7 suggest this may not be the case with ribociclib . Given limited therapeutic options in the post-CDK4/6i setting, it is vital to address existing knowledge gaps.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Cyclin-Dependent Kinase 4/6 Inhibitors for Treatment of Hormone Receptor–Positive, ERBB2-Negative Breast Cancer

et al. 2023

View full text Add to dashboard Cite

ImportanceCombination therapy with cyclin-dependent kinase 4 and 6 inhibitors (CDK4/6i: palbociclib, ribociclib, abemaciclib) and endocrine therapy (ET) has been a major advance for the treatment of hormone receptor–positive (HR+), ERBB2 (formerly HER2)–negative (ERBB2−) advanced or metastatic breast cancer.ObservationsRandomized phase 3 studies demonstrated that the addition of CDK4/6i reduced the hazard risk of disease progression by approximately half compared with hormonal monotherapy (an aromatase inhibitor, tamoxifen, or fulvestrant) in the first-line (1L) and/or second-line (2L) setting. Hence, the US Food and Drug Administration and European Medicines Agency approved 3 CDK4/6i, in both 1L and 2L settings. However, differences among the CDK4/6i regarding mechanisms of action, adverse effect profiles, and overall survival (OS) are emerging. Both abemaciclib and ribociclib have demonstrated efficacy in high-risk HR+ early breast cancer. While ET with or without CDK4/6i is accepted as standard treatment for persons with advanced HR+ ERBB2− metastatic breast cancer, several key issues remain. First, why are there discordances in OS in the metastatic setting and efficacy differences in the adjuvant setting? Additionally, apart from HR status, there are few biomarkers predictive of response to CDK4/6i plus ET, and these are not used routinely. Despite the clear OS advantage noted in the 1L and 2L metastatic setting with some CDK4/6i, a subset of patients with highly endocrine-sensitive disease do well with ET alone. Therefore, an unanswered question is whether some patients can postpone CDK4/6i until the 2L setting, particularly if financial toxicity is a concern. Finally, given the lack of endocrine responsiveness following progression on some CDK4/6i, strategies to optimally sequence treatment are needed.Conclusions and RelevanceFuture research should focus on defining the role of each CDK4/6i in HR+ breast cancer and developing a biomarker-directed integration of these agents.

show abstract

Section: Endocrine Sensitivity After Cdk4/6imentioning

confidence: 79%

Section: Introductionmentioning

confidence: 99%