nextMONARCH: Abemaciclib Monotherapy or Combined With Tamoxifen for Metastatic Breast Cancer

Hamilton, Erika; Cortés, Javier; Ozyilkan, Ozgür; Chen, Shin‐Cheh; Manikhas, A.; Jérusalem, Guy; Hegg, Roberto; Huober, Jens; Chapman, Sonya C.; Lü, Yi; Hardebeck, Molly Catherine; Bear, Melissa; Johnston, Erica L.; Martı́n, Miguel

doi:10.1016/j.clbc.2020.09.011

Cited by 32 publications

(38 citation statements)

References 17 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This is consistent with the safety profile observed in subsequent studies; besides diarrhea, the most common AEs of any grade reported in patients receiving abemaciclib plus NSAI in MONARCH 3 included neutropenia (41.3%), fatigue (40.1%), infections (39.1%), nausea (38.5%), and abdominal pain (29.1%) (7), although the rates of fatigue, nausea, and abdominal pain were higher in this study (Parts A-D). Similar to patients in Part C of our study, the most common AEs reported for patients receiving abemaciclib plus tamoxifen in the nextMONARCH study included diarrhea (53.8%), neutropenia (41.0%), anemia (39.7%), infections (32.1%), nausea (30.8%), fatigue (29.5%), leukopenia (26.9%), and abdominal pain (26.9%) (13). In Parts A-D of this Phase 1b study, no unexpected safety signals were observed, and treatment discontinuation due to AEs was not common (11 patients, 16.4%).…”

Section: Discussionsupporting

confidence: 65%

“…Subsequent studies have evaluated the efficacy and tolerability of abemaciclib in combination with ET in patients with advanced breast cancer or MBC, including fulvestrant (MONARCH 2), NSAI (MONARCH 3), and tamoxifen (nextMONARCH) ( 7 , 8 , 13 ). In the MONARCH 2 trial, abemaciclib plus fulvestrant significantly improved the PFS (median 16.4 vs. 9.3 months) and ORR (48.1% vs. 21.3%) compared with placebo plus fulvestrant and exhibited a good safety profile in patients with HR+, HER2– advanced breast cancer who had progressed while receiving ET ( 8 ).…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Abemaciclib in Combination With Endocrine Therapy for Patients With Hormone Receptor-Positive, HER2-Negative Metastatic Breast Cancer: A Phase 1b Study

et al. 2022

Self Cite

View full text Add to dashboard Cite

BackgroundCyclin-dependent kinases (CDK) 4 and 6 regulate G1 to S cell cycle progression and are often altered in cancers. Abemaciclib is a selective inhibitor of CDK4 and CDK6 approved for administration on a continuous dosing schedule as monotherapy or as combination therapy with an aromatase inhibitor or fulvestrant in patients with advanced or metastatic breast cancer. This Phase 1b study evaluated the safety and tolerability, pharmacokinetics, and antitumor activity of abemaciclib in combination with endocrine therapy for metastatic breast cancer (MBC), including aromatase inhibitors (letrozole, anastrozole, or exemestane) or tamoxifen.Patients and MethodsWomen ≥18 years old with hormone receptor positive (HR+), human epidermal growth factor receptor 2 negative (HER2-) MBC were eligible for enrollment. Eligibility included measurable disease or non-measurable but evaluable bone disease by Response Evaluation Criteria in Solid Tumours (RECIST) v1.1, Eastern Cooperative Oncology Group performance status 0–1, and no prior chemotherapy for metastatic disease. Adverse events were graded by the National Cancer Institute Common Terminology Criteria for Adverse Events v4.0 and tumor response were assessed by RECIST v1.1.ResultsSixty-seven patients were enrolled and received abemaciclib 200 mg every 12 hours in combination with letrozole (Part A, n=20), anastrozole (Part B, n=16), tamoxifen (Part C, n=16), or exemestane (Part D, n=15). The most common treatment-emergent adverse events (TEAE) were diarrhea, fatigue, nausea, and abdominal pain. Grade 4 TEAEs were reported in five patients (one each with hyperglycemia, hypertension, neutropenia, procedural hemorrhage, and sepsis). There was no effect of abemaciclib or endocrine therapy on the pharmacokinetics of any combination study drug. Across all treated patients, the median progression-free survival was 25.4 months (95% confidence interval: 18.0, 35.8). The objective response rate was 38.9% in 36 patients with measurable disease.ConclusionsAbemaciclib in combination with multiple endocrine therapy options exhibited manageable safety and promising antitumor activity in patients with HR+, HER2- MBC.Clinical Trial Registrationhttps://clinicaltrials.gov/, identifier NCT02057133

show abstract

Section: Discussionsupporting

confidence: 65%

Section: Discussionmentioning

confidence: 99%

Abemaciclib in Combination With Endocrine Therapy for Patients With Hormone Receptor-Positive, HER2-Negative Metastatic Breast Cancer: A Phase 1b Study

et al. 2022

Self Cite

View full text Add to dashboard Cite

show abstract

“…Another trial using abemaciclib sought to see if this difference was observed using a different CDK4/6 inhibitor, which is important because abemaciclib is the only one currently approved in some cases as a monotherapy. The nextMONARCH trial included HR+/HER2-metastatic breast cancer patients who previously received chemotherapy and divided them into three groups [78]. The monotherapy group received 150 mg abemaciclib every 12 h. Another group was given 200 mg abemaciclib every 12 h, along with loperamide to help manage the common adverse effect of early-onset diarrhea that is experienced with high doses of abemaciclib.…”

Section: Antiestrogensmentioning

confidence: 99%

Resistance to CDK4/6 Inhibitors in Estrogen Receptor-Positive Breast Cancer

Scheidemann

Shajahan-Haq

2021

IJMS

View full text Add to dashboard Cite

Estrogen receptor-positive (ER+) breast cancer is the most common form of breast cancer. Antiestrogens were the first therapy aimed at treating this subtype, but resistance to these warranted the development of a new treatment option. CDK4/6 inhibitors address this problem by halting cell cycle progression in ER+ cells, and have proven to be successful in the clinic. Unfortunately, both intrinsic and acquired resistance to CDK4/6 inhibitors are common. Numerous mechanisms of how resistance occurs have been identified to date, including the activation of prominent growth signaling pathways, the loss of tumor-suppressive genes, and noncanonical cell cycle function. Many of these have been successfully targeted and demonstrate the ability to overcome resistance to CDK4/6 inhibitors in preclinical and clinical trials. Future studies should focus on the development of biomarkers so that patients likely to be resistant to CDK4/6 inhibition can initially be given alternative methods of treatment.

show abstract

“…The use of CDK4/6 inhibitors is standard in combination with the endocrine therapy of an AI, whereas a combination with fulvestrant is preferable in patients who show progressive disease or relapse under AI [ 11 ]. Abemaciclib has also been approved as an monotherapeutic agent in heavily pretreated HR+, HER2− MBC patients [ 12 ]. CDK4/6 inhibitors have significantly improved the progression-free survival (PFS) by several months, compared to endocrine treatment alone, in prospective, randomized clinical trials ( Table 1 ) [ 13 ].…”

Section: The Rationale Of Targeting Cdk4/6 For Breast Cancer Therapymentioning

confidence: 99%

Targeted Therapy in HR+ HER2− Metastatic Breast Cancer: Current Clinical Trials and Their Implications for CDK4/6 Inhibitor Therapy and beyond Treatment Options

Elfgen

Bjelic‐Radisic

2021

Cancers

View full text Add to dashboard Cite

A metastatic state of breast cancer (MBC) affects hundreds of thousands of women worldwide. In hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2−) MBC, cyclin-dependent kinase (CDK)4/6 inhibitors can improve the progression-free survival (PFS), as well as the overall survival (OS), in selected patients and have been established as first- and second-line therapies. However, as MBC remains uncurable, resistance to CDK4/6 inhibitors occurs and requires alternative treatment approaches. Data on targeted therapy continue to mature, and the number of publications has been constantly rising. This review provides a summary and update on the clinical relevance, patient selection, ongoing trials of CDK4/6 inhibitors, and further targeted therapy options. It focuses on clinical aspects and practicability, as well as adverse events and patient-reported outcomes.

show abstract

nextMONARCH: Abemaciclib Monotherapy or Combined With Tamoxifen for Metastatic Breast Cancer

Cited by 32 publications

References 17 publications

Abemaciclib in Combination With Endocrine Therapy for Patients With Hormone Receptor-Positive, HER2-Negative Metastatic Breast Cancer: A Phase 1b Study

Abemaciclib in Combination With Endocrine Therapy for Patients With Hormone Receptor-Positive, HER2-Negative Metastatic Breast Cancer: A Phase 1b Study

Resistance to CDK4/6 Inhibitors in Estrogen Receptor-Positive Breast Cancer

Targeted Therapy in HR+ HER2− Metastatic Breast Cancer: Current Clinical Trials and Their Implications for CDK4/6 Inhibitor Therapy and beyond Treatment Options

Contact Info

Product

Resources

About