Dataset Information

MONARCH plus: abemaciclib plus endocrine therapy in women with HR+/HER2- advanced breast cancer: the multinational randomized phase III study.

ABSTRACT:

Aim

To compare the efficacy, safety, and tolerability of abemaciclib plus endocrine therapy (ET) versus ET alone in postmenopausal women with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer (ABC) from China, Brazil, India, and South Africa.

Methods

This randomized, double-blind, phase III study was conducted between 9 December 2016 and 29 March 2019. Postmenopausal women with HR-positive, HER2-negative ABC with no prior systemic therapy in an advanced setting (cohort A) or progression on prior ET (cohort B) received abemaciclib (150 mg twice daily) or placebo plus: anastrozole (1 mg/day) or letrozole (2.5 mg/day) (cohort A) or fulvestrant (500 mg per label) (cohort B). The primary endpoint was progression-free survival (PFS) in cohort A, analyzed using the stratified log-rank test. Secondary endpoints were PFS in cohort B (key secondary endpoint), objective response rate (ORR), and safety. This interim analysis was planned after 119 PFS events in cohort A.

Results

In cohort A, 207 patients were randomly assigned to the abemaciclib arm and 99 to the placebo arm. Abemaciclib significantly improved PFS versus placebo (median: not reached versus 14.7 months; hazard ratio 0.499; 95% confidence intervals (CI) 0.346-0.719; p = 0.0001). ORR was 65.9% in the abemaciclib arm and 36.1% in the placebo arm (p < 0.0001, measurable disease population). In cohort B, 104 patients were randomly assigned to the abemaciclib arm and 53 to the placebo arm. Abemaciclib significantly improved PFS versus placebo (median: 11.5 versus 5.6 months; hazard ratio 0.376; 95% CI 0.240-0.588; p < 0.0001). ORR was 50.0% in the abemaciclib arm and 10.5% in the placebo arm (p < 0.0001, measurable disease population). The most frequent grade ⩾3 adverse events in the abemaciclib arms were neutropenia, leukopenia, and anemia (both cohorts), and lymphocytopenia (cohort B).

Conclusion

The addition of abemaciclib to ET demonstrated significant and clinically meaningful improvement in PFS and ORR, without new safety signals observed in this population.Trial Registration: ClinicalTrials.gov identifier: NCT02763566.

SUBMITTER: Zhang QY

PROVIDER: S-EPMC7586037 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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MONARCH plus: abemaciclib plus endocrine therapy in women with HR+/HER2- advanced breast cancer: the multinational randomized phase III study.

Zhang Qing Yuan QY Sun Tao T Yin Yong Mei YM Li Hui Ping HP Yan Min M Tong Zhong Sheng ZS Oppermann Christina P CP Liu Yun Peng YP Costa Romulo R Li Man M Cheng Ying Y Ouyang Qu Chang QC Chen Xi X Liao Ning N Wu Xin Hong XH Wang Xiao Jia XJ Feng Ji Feng JF Hegg Roberto R Kanakasetty G B GB Coccia-Portugal Maria A MA Han Ru Bing RB Lu Yi Y Chi Hai Dong HD Jiang Ze Fei ZF Hu Xi Chun XC

Therapeutic advances in medical oncology 20201022

<h4>Aim</h4>To compare the efficacy, safety, and tolerability of abemaciclib plus endocrine therapy (ET) <i>versus</i> ET alone in postmenopausal women with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer (ABC) from China, Brazil, India, and South Africa.<h4>Methods</h4>This randomized, double-blind, phase III study was conducted between 9 December 2016 and 29 March 2019. Postmenopausal women with HR-positive, HER2-negative ABC with ...[more]

PMID: 33149768

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Project description:BackgroundMONARCH 3, a phase III trial (NCT02246621) of postmenopausal women with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer (ABC), previously demonstrated significantly improved progression-free survival in patients receiving abemaciclib plus a nonsteroidal aromatase inhibitor (NSAI). This study evaluated patient-reported outcomes, including global health-related quality of life (HRQoL), functioning, and symptoms.MethodsPatients were randomly assigned 2:1 to receive abemaciclib (150 mg twice daily; n = 328) or placebo (n = 165), plus 1 mg anastrozole or 2.5 mg letrozole daily. The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 and Breast Cancer-Specific Quality of Life Questionnaire HRQoL instruments were administered at baseline, every two cycles during cycles 2 through 19 (each cycle being 28 days), every three cycles thereafter, and once at a short-term posttherapy follow-up visit (approximately 30 days after discontinuation). Longitudinal mixed regression and Cox proportional hazards models evaluated postbaseline change and time to sustained deterioration (TTSD), respectively.ResultsBaseline scores were similar between treatment arms. Although select scores statistically favored the placebo arm, global HRQoL, most symptoms, and functioning scales did not meet the threshold for clinically meaningful differences between treatment arms. Only diarrhea favored the placebo arm with statistically and clinically meaningful differences. There were no TTSD differences between treatment arms for global HRQoL, most symptoms (except diarrhea), or functioning.ConclusionOver a 2-year period, there were no clinically meaningful differences in global HRQoL, functioning, and most symptoms for patients receiving abemaciclib plus NSAI compared with NSAI alone. Only diarrhea favored the placebo arm, consistent with prior safety data, which has been shown to be manageable and reversible. Combined with clinical efficacy, results support treatment with abemaciclib plus NSAI for postmenopausal women with HR+, HER2- ABC.Implications for practiceThe addition of abemaciclib to a nonsteroidal aromatase inhibitor (NSAI) was not associated with a clinically meaningful detriment in patient-reported global health-related quality of life, functioning, and most symptoms in postmenopausal women with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer (ABC). Prior studies have also demonstrated clinical efficacy of abemaciclib plus NSAI compared with NSAI alone, including improved progression-free survival and objective response rate. These results also complement previously reported toxicity data, as measured by investigator-assessed adverse events. Taken together, these results support treatment with abemaciclib plus NSAI for postmenopausal women with HR+, HER2- ABC.

Project description:BackgroundIn the phase III MONARCH 2 study (NCT02107703), abemaciclib plus fulvestrant significantly improved progression-free survival (PFS) versus placebo plus fulvestrant in patients with hormone receptor-positive (HR+), HER2-negative advanced breast cancer (ABC). This study assessed patient-reported pain, global health-related quality of life (HRQoL), functioning, and symptoms.Materials and methodsAbemaciclib or placebo (150 p.o. mg twice daily) plus fulvestrant (500 mg, per label) were randomly assigned (2:1). The modified Brief Pain Inventory, Short Form (mBPI-sf); European Organization for Research and Treatment of Cancer (EORTC) QoL Core 30 (QLQ-C30); and Breast Cancer Questionnaire (QLQ-BR23) assessed outcomes. Data were collected at baseline, cycle 2, every two cycles 3-13, thereafter at every three cycles, and 30 days postdiscontinuation. Longitudinal mixed regression and Cox proportional hazards models assessed postbaseline change and time to sustained deterioration (TTSD) by study arm.ResultsOn-treatment HRQoL scores were consistently maintained from baseline and similar between arms. Patients in the abemaciclib arm (n = 446) experienced a 4.9-month delay in pain deterioration (mBPI-sf), compared with the control arm (n = 223), and significantly greater TTSD on the mBPI-sf and analgesic use (hazard ratio, 0.76; 95% CI, 0.59-0.98) and QLQ-C30 pain item (hazard ratio, 0.62; 95% CI, 0.48-0.79). TTSD for functioning and most symptoms significantly favored the abemaciclib arm, including fatigue, nausea and vomiting, and cognitive and social functioning. Only diarrhea significantly favored the control arm (hazard ratio, 1.60; 95% CI, 1.20-2.10).ConclusionHRQoL was maintained on abemaciclib plus fulvestrant. Alongside superior PFS and manageable safety profile, results support treatment with abemaciclib plus fulvestrant in a population of patients with endocrine-resistant HR+, HER2-negative ABC.Implications for practiceIn MONARCH 2, abemaciclib plus fulvestrant demonstrated superior efficacy and a manageable safety profile for patients with in hormone receptor-positive (HR+), HER2-negative (-) advanced breast cancer (ABC). Impact on health-related quality of life (HRQoL) is important to consider, given the palliative nature of ABC treatment. In this study, abemaciclib plus fulvestrant, compared with placebo plus fulvestrant, significantly delayed sustained deterioration of pain and other patient-reported symptoms (including fatigue, nausea, vomiting), and social and cognitive functioning. Combined with demonstrated clinical benefit and tolerability, the stabilization of patient-reported symptoms and HRQoL further supports abemaciclib plus fulvestrant as a desirable treatment option in endocrine resistant, HR+, HER2- ABC.

Project description:Introduction: This study evaluated the cost-effectiveness of abemaciclib plus fulvestrant (ABE + FUL) vs. palbociclib plus fulvestrant (PAL + FUL), ribociclib plus fulvestrant (RIB + FUL) and fulvestrant monotherapy (FUL) as second-line treatment for hormone receptor-positive and human epidermal growth factor receptor 2- negative advanced or metastatic breast cancer in the US. Methods: The 3 health states partitioned survival (PS) model was used over the lifetime. Effectiveness and safety data were derived from the MONARCH 2 trial, MONALEESA-3 trial, and PALOMA-3 trial. Parametric survival models were used for four treatments to explore the long-term effect. Costs were derived from the pricing files of Medicare and Medicaid Services, and utility values were derived from published studies. Sensitivity analyses including one-way sensitivity analysis, probabilistic sensitivity analysis and scenario analysis were performed to observe model stability. Results: In the PS model, compared with PAL + FUL, ABE + FUL yielded 0.44 additional QALYs at an additional cost of $100,696 for an incremental cost-utility ratio (ICUR) of $229,039/QALY. Compared with RIB + FUL, ABE + FUL yielded 0.03 additional QALYs at an additional cost of $518 for an ICUR of $19,314/QALY. Compared with FUL, ABE + FUL yielded 0.68 additional QALYs at an additional cost of $260,584 for ICUR of $381,450/QALY. From the PS model, the ICUR was $270,576 /QALY (ABE + FUL vs. PAL + FUL), dominated (ABE + FUL vs. RIB + FUL) and $404,493/QALY (ABE + FUL vs. FUL) in scenario analysis. In the probabilistic sensitivity analysis, the probabilities that ABE + FUL was cost-effective vs. PAL + FUL, RIB + FUL and FUL at thresholds of $50,000, $100,000, and $200,000 per QALY gained were 0% and the probabilities that ABE + FUL was cost-effective vs. PAL + FUL and RIB + FUL at thresholds of $50,000, $100,000, and $200,000 per QALY gained were 0.2, 0.6, and 7.3%. Conclusions: The findings from the present analysis suggest that ABE + FUL might be cost-effective compared with RIB + FUL and not cost-effective compared with PAL + FUL and FUL for second-line treatment of patients with HR+/HER2- advanced or metastatic breast cancer in the US.

Dataset Information

MONARCH plus: abemaciclib plus endocrine therapy in women with HR+/HER2- advanced breast cancer: the multinational randomized phase III study.

Aim

Methods

Results

Conclusion

Publications

MONARCH plus: abemaciclib plus endocrine therapy in women with HR+/HER2- advanced breast cancer: the multinational randomized phase III study.

Similar Datasets

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