Browsing by Author "Manikhas, Aleksey"

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    nextMONARCH Phase 2 randomized clinical trial: overall survival analysis of abemaciclib monotherapy or in combination with tamoxifen in patients with endocrine-refractory HR +, HER2-metastatic breast cancer
    (2022) Hamilton, Erika; Cortes, Javier; Ozyilkan, Ozgur; Chen, Shin-Cheh; Petrakova, Katarina; Manikhas, Aleksey; Jerusalem, Guy; Hegg, Roberto; Huober, Jens; Zhang, Wei; Chen, Yanyun; Martin, Miguel; 35829935
    Purpose Resistance to endocrine therapy poses a major clinical challenge for patients with hormone receptor-positive (HR +), human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer (MBC). We present the preplanned 24-month final overall survival (OS) results, alongside updated progression-free survival (PFS), and objective response rate (ORR) results. Methods nextMONARCH is an open-label, controlled, randomized, Phase 2 study of abemaciclib alone or in combination with tamoxifen in women with endocrine-refractory HR + , HER2- MBC previously treated with chemotherapy. Patients were randomized 1:1:1 to: abemaciclib 150 mg and tamoxifen 20 mg (A + T), abemaciclib 150 mg (A-150), or abemaciclib 200 mg and prophylactic loperamide (A-200). OS was the main prespecified secondary endpoint. PFS, ORR, and safety at 24 months were compared to previously reported primary analysis results. Results Of the 234 patients enrolled, 12 were receiving study treatment at data cutoff (28Jun2019). Median follow-up was 27.2 months. Median OS was 24.2 months in the A + T arm, 20.8 months in A-150, and 17.0 months in A-200 (A + T versus A-200: HR 0.62; 95%CI [0.40, 0.97], P = 0.03 and A-150 versus A-200: HR 0.96; 95%CI [0.64, 1.44], P = 0.83). PFS and ORR results at 24 months were consistent with the primary analysis. The safety profile corresponded with previous reports. Conclusion The addition of tamoxifen to abemaciclib demonstrated greater OS benefit than monotherapy. This study confirmed the single-agent activity of abemaciclib in heavily pretreated women with endocrine-refractory HR + , HER2- MBC, as well as the previously reported primary PFS and ORR results, with no new safety signals observed.
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    nextMONARCH: Abemaciclib Monotherapy or Combined With Tamoxifen for Metastatic Breast Cancer
    (2021) Hamilton, Erika; Cortes, Javier; Ozyilkan, Ozgur; Chen, Shin Cheh; Petrakova, Katarina; Manikhas, Aleksey; Jerusalem, Guy; Hegg, Roberto; Huober, Jens; Chapman, Sonya C.; Lu, Yi; Hardebeck, Molly C.; Bear, Melissa M.; Johnston, Erica L.; Martin, Miguel; 0000-0001-8825-4918; 33148479; AAD-2817-2021
    nextMONARCH investigated abemaciclib monotherapy and abemaciclib combined with tamoxifen. Patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative metastatic breast cancer (MBC) were treated with abemaciclib (with or without prophylactic loperamide) and combined with tamoxifen for endocrine refractory MBC after chemotherapy. The results confirmed the single-agent activity of abemaciclib in heavily pretreated hormone receptor-positive, human epidermal growth factor receptor 2-negative MBC. Background: Abemaciclib is a selective cyclin-dependent kinase 4 and 6 inhibitor administered continuously for hormone receptor-positive (HR*), human epidermal growth factor receptor 2-negative (HER2(-)) advanced breast cancer. Abemaciclib is associated with dose-dependent early-onset diarrhea. nextMONARCH evaluated abemaciclib monotherapy (with or without prophylactic loperamide) and combined with tamoxifen for endocrine refractory metastatic breast cancer (MBC) after chemotherapy. Patients and Methods: nextMONARCH is an open-label, controlled, randomized, phase II study of women with endocrine-refractory HR+, HER2(-) MBC previously treated with chemoherapy. Patients received abemaciclib 150 mg plus tamoxifen 20 mg (A+T), abemaciclib 150 mg every 12 hours (A-150), or abemaciclib 200 mg plus prophylactic loperamide (A-200). The primary objective was progression-free survival (PFS). PFS analyses tested superiority of A+T to A-200 and informal noninferiority of A-150 to A-200. The secondary objectives included the objective response rate (ORR), safety, and pharmacokinetics. Results: The median PFS was 9.1 months for A+T versus 7.4 months for A-200 (hazard ratio, 0.815; 95% confidence interval, 0.556-1.193; P = .293). The A-200 PFS was comparable to that with A-150 at 6.5 months (hazard ratio, 1.045; 95% confidence nterval, 0.711-1.535; P = .811). The ORR was 34.6%, 24.1%, and 32.5% for A+T, A-150, and A-200, respectively. No new safety signals were identified. The incidence and severity of diarrhea (62.3%; grade 3, 7.8%) with A-200 was similar to that with A-150 (67.1%; grade 3, 3.8%). The pharmacokinetics were comparable to previous observations. Conclusions: The addition of tamoxifen to abemaciclib did not significantly improve PFS or ORR compared with abemaciclib monotherapy but confirmed the single-agent activity of abemaciclib in heavily pretreated HR+, HER2(-) MBC. Dose reductions and antidiarrheal medication generally managed diarrhea while maintaining efficacy. (C) 2020 Published by Elsevier Inc.