Verzenio – pro
Verzenio was initially s FDA approved in combination with fulvestrant to treat women with hormone receptor (HR)–positive, human epidermal growth factor receptor 2 (HER2)–negative advanced breast cancer or breast cancer that has spread to other parts of the body (metastatic), whose disease has progressed after hormonal therapy alone to treat adults with HR–positive, HER2–negative advanced breast cancer or metastatic breast cancer whose disease has progressed after hormonal therapy and prior chemotherapy.
FDA also approved Verzenio (abemaciclib) in combination with an aromatase inhibitor (AI) as initial endocrine-based therapy for the treatment of postmenopausal women with hormone receptor-positive (HR+), human epidermal growth factor 2-negative (HER2-) advanced or metastatic breast cancer.
There also was a neoMonarch study, a phase II study. It was a randomized, multi-center, open-label study that enrolled 224 patients who had at least one measurable tumor ≥1 cm, adequate organ function, and an ECOG performance status of ≤1. Patients were randomized to one of three trial arms: 1) twice-daily abemaciclib monotherapy (150mg) for two weeks; 2) twice-daily abemaciclib (150mg) along with once-daily anastrozole (1mg) for two weeks; or 3) once-daily anastrozole monotherapy (1mg) for two weeks. All patients received an initial biopsy prior to randomization to assess baseline Ki67 expression. After the initial two-week treatment period, patients underwent a second tumor biopsy and Ki67 was assessed again. Eli Lilly-results showed abemaciclib monotherapy, abemaciclib in combination with anastrozole significantly reduced KI67 more than anastrozole alone.
The latest approval was supported by data from the Phase 3, randomized, double-blind, placebo-controlled MONARCH 3 trial which evaluated Verzenio in combination with an AI (anastrozole or letrozole) in 493 postmenopausal women with HR+, HER2- advanced breast cancer who had no prior systemic treatment for advanced disease. The primary endpoint was progression-free survival (PFS); secondary endpoints included overall response rate (ORR), duration of response (DoR), overall survival and safety.
Verzenio 150mg twice daily given continuously with an AI showed a greater 28-month median PFS in patients who received initial endocrine-based therapy for metastatic disease vs placebo with an AI (28.2 months vs. 14.8 months; hazard ratio [HR] 0.54, 95% CI: 0.418–0.698; P<0.0001).
For adjuvant therapy, The Monarch study was an open-label, phase III study that included patients with HR+, HER2−, high-risk EBC, who had surgery and, as indicated, radiotherapy and/or adjuvant/neoadjuvant chemotherapy. Patients with four or more positive nodes, or one to three nodes and either tumor size ≥ 5 cm, histologic grade 3, or central Ki-67 ≥ 20%, were eligible and randomly assigned (1:1) to standard-of-care adjuvant endocrine therapy (ET) with or without abemaciclib (150 mg twice daily for 2 years). The primary endpoint was invasive disease-free survival (IDFS), and secondary endpoints included distant relapse-free survival, overall survival, and safety. For adjuvant therapy, the Monarch E study showed that Abemaciclib + ET significantly improved IDFS in patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative, node-positive, high-risk early breast cancer, with an acceptable safety profile. Ki-67 index was prognostic, but abemaciclib benefit was observed regardless of Ki-67 index. Overall, the robust treatment benefit of abemaciclib extended beyond the 2-year treatment period.
Monarch E study showed that Abemaciclib + ET significantly improved IDFS in patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative, node-positive, high-risk early breast cancer, with an acceptable safety profile. Ki-67 index was prognostic, but abemaciclib benefit was observed regardless of Ki-67 index. Overall, the robust treatment benefit of abemaciclib extended beyond the 2-year treatment period.
S R D Johnoson et al, Abemaciclib Combined With Endocrine Therapy for the Adjuvant Treatment of HR+, HER2, Node-Positive, High-Risk, Early Breast Cancer (monarchE) JCO linical Oncology 38, no. 34 (December 01, 2020) 3987-3998.
George W. Sledge et al, MONARCH 2: Abemaciclib in Combination With Fulvestrant in Women With HR+/HER2? Advanced Breast Cancer Who Had Progressed While Receiving Endocrine Therapy. Journal of Clinical Oncology 35, no. 25 (September 2017) 2875-2884.
Verzenio, Prescribing Information 2022
Harbeck N, Rastogi P, Martin M, Tolaney SM, Shao ZM, Fasching PA, Huang CS, Jaliffe GG, Tryakin A, Goetz MP, Rugo HS, Senkus E, Testa L, Andersson M, Tamura K, Del Mastro L, Steger GG, Kreipe H, Hegg R, Sohn J, Guarneri V, Cortés J, Hamilton E, André V, Wei R, Barriga S, Sherwood S, Forrester T, Munoz M, Shahir A, San Antonio B, Nabinger SC, Toi M, Johnston SRD, O’Shaughnessy J; monarchE Committee Members. Adjuvant abemaciclib combined with endocrine therapy for high-risk early breast cancer: updated efficacy and Ki-67 analysis from the monarchE study. Ann Oncol. 2021 Dec;32(12):1571-1581. doi: 10.1016/j.annonc.2021.09.015. Epub 2021 Oct 14. PMID: 34656740.