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Health-related quality of life in premenopausal women with hormone-receptor-positive, HER2-negative advanced breast cancer treated with ribociclib plus endocrine therapy: results from a phase III randomized clinical trial (MONALEESA-7).

ABSTRACT: Background:This analysis evaluated patient-reported outcomes (PROs) to assess health-related quality of life (HRQoL) in the phase?III MONALEESA-7 trial, which previously demonstrated improvements in progression-free survival (PFS) and overall survival (OS) with ribociclib (cyclin-dependent kinase 4/6 inhibitor)?+?endocrine therapy (ET) compared with placebo?+?ET in pre- and perimenopausal patients with hormone-receptor-positive, HER2-negative (HR+/HER2-) advanced breast cancer (ABC). Methods:The European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life questionnaire C30 (QLQ-C30) and the EQ-5D-5L were used to evaluate HRQoL. Results:EORTC QLQ-C30 assessments were evaluable for 335 patients in the ribociclib arm and 337 patients in the placebo arm. Adherence rates at baseline and ?1 postbaseline time point were 90% and 83%, respectively. Patients treated with ribociclib?+?ET had a longer time to deterioration (TTD)???10% in global HRQoL {hazard ratio (HR), 0.67 [95% confidence interval (CI), 0.52-0.86]}. TTD???10% in global HRQoL was delayed in ribociclib-treated patients without versus with disease progression [HR, 0.31 (95% CI, 0.21-0.48)]. TTD???10% in pain was longer with ribociclib?+?ET than with placebo?+?ET [HR, 0.65 (95% CI, 0.45-0.92)]. Patients who received a nonsteroidal aromatase inhibitor experienced similar benefits with ribociclib versus placebo in global HRQoL and pain. Conclusion:HRQoL was maintained longer in patients who received ribociclib?+?ET versus placebo?+?ET. These data, combined with previously reported improvements in PFS and OS, support a strong clinical benefit-to-risk ratio with ribociclib-based treatment in pre- and perimenopausal patients with HR+/HER2- ABC.

SUBMITTER: Harbeck N

PROVIDER: S-EPMC7385843 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Health-related quality of life in premenopausal women with hormone-receptor-positive, HER2-negative advanced breast cancer treated with ribociclib plus endocrine therapy: results from a phase III randomized clinical trial (MONALEESA-7).

Harbeck Nadia N Franke Fabio F Villanueva-Vazquez Rafael R Lu Yen-Shen YS Tripathy Debu D Chow Louis L Babu Govind K GK Im Young-Hyuck YH Chandiwana David D Gaur Anil A Lanoue Brad B Rodriguez-Lorenc Karen K Bardia Aditya A

Therapeutic advances in medical oncology 20200726

<h4>Background</h4>This analysis evaluated patient-reported outcomes (PROs) to assess health-related quality of life (HRQoL) in the phase III MONALEESA-7 trial, which previously demonstrated improvements in progression-free survival (PFS) and overall survival (OS) with ribociclib (cyclin-dependent kinase 4/6 inhibitor) + endocrine therapy (ET) compared with placebo + ET in pre- and perimenopausal patients with hormone-receptor-positive, HER2-negative (HR+/HER2-) advanced breast cancer (ABC).<h4> ...[more]

PMID: 32782490

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Project description:BackgroundThe CDK4/6 inhibitor, ribociclib in combination with endocrine therapy significantly improved progression-free survival in the first line setting in post-menopausal patients with HR+/HER2- advanced breast cancer (ABC) in a pivotal phase 3, placebo-controlled trial (MONALEESA-2) and demonstrated superior overall survival in premenopausal patients with HR+/HER2- ABC (MONALEESA-7). The multinational, phase 3b, CompLEEment-1 trial, which assessed the safety and efficacy of ribociclib plus letrozole in a broader population of patients who have not received prior endocrine therapy for advanced disease, is the largest phase 3 clinical trial to date to evaluate the safety and efficacy of a CDK4/6 inhibitor. We report a subanalysis of data from patients (N = 339) enrolled in the central and south European countries of the SERCE (Southern Europe, RUC, Central Europe) cluster of CompLEEment-1.Patients and methodsMen and women of any menopausal status with HR+/HER2- ABC received once-daily oral ribociclib 600 mg (3-weeks on/1-week-off), plus letrozole 2.5 mg continuously. Men/premenopausal women also received a GnRH-agonist. The primary outcome was the number of patients with adverse events (AEs) over a timeframe of approximately 36 months. Time-to-progression, overall response rate, and clinical benefit rate were also measured.ResultsSafety results in the SERCE subgroup were consistent with those in the pivotal clinical trials of ribociclib in combination with endocrine therapy. Treatment-related AEs leading to dose adjustments/interruption occurred in 63.1% of patients but led to treatment discontinuation in only 10.6%. The most common treatment-related AEs of grade ≥ 3 were neutropenia and transaminase elevations. There were no fatal treatment-related events.ConclusionsThese findings from the SERCE subgroup support the safety and manageable tolerability of ribociclib in a broad range of patients with HR+/HER2- ABC more representative of patients in real-world clinical practice.

Project description:BackgroundThe phase III MONALEESA-3 trial included first- (1L) and second-line (2L) patients and demonstrated a significant overall survival (OS) benefit for ribociclib + fulvestrant in patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative (HR+/HER2-) advanced breast cancer (ABC) in the final protocol-specified and exploratory (longer follow-up) OS analyses. At the time of these analyses, the full OS benefit of 1L ribociclib was not completely characterized because the median OS (mOS) was not reached. As CDK4/6 inhibitor (CDK4/6i) + endocrine therapy (ET) is now a preferred option for 1L HR+/HER2- ABC, we report an exploratory analysis (median follow-up, 70.8 months; 14.5 months longer than the prior analysis) to fully elucidate the OS benefit in the MONALEESA-3 1L population.MethodsPostmenopausal patients with HR+/HER2- ABC were randomized 2:1 to 1L/2L fulvestrant + ribociclib or placebo. OS in 1L patients (de novo disease or relapse > 12 months from completion of [neo]adjuvant ET) was assessed by Cox proportional hazards model and Kaplan-Meier methods. Progression-free survival 2 (PFS2) and chemotherapy-free survival (CFS) were analyzed. MONALEESA-3 is registered with ClinicalTrials.gov (NCT02422615).ResultsAt data cutoff (January 12, 2022; median follow-up time, 70.8 months), mOS was 67.6 versus 51.8 months with 1L ribociclib versus placebo (hazard ratio (HR) 0.67; 95% CI 0.50-0.90); 16.5% and 8.6% of ribociclib and placebo patients, respectively, were still receiving treatment. PFS2 (HR 0.64) and CFS (HR 0.62) favored ribociclib versus placebo. Among those who discontinued treatment, 16.7% and 35.0% on ribociclib or placebo, respectively, received a subsequent CDK4/6i. No new safety signals were observed.ConclusionsThis analysis of MONALEESA-3 reports the longest mOS thus far (67.6 months) for 1L patients in a phase III ABC trial. These results in a 1L population show that the OS benefit of ribociclib was maintained through extended follow-up, further supporting its use in HR+/HER2- ABC.

Project description:BACKGROUND:In 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 METHODS:Abemaciclib 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. RESULTS:On-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). CONCLUSION:HRQoL 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 PRACTICE:In 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.

Dataset Information

Health-related quality of life in premenopausal women with hormone-receptor-positive, HER2-negative advanced breast cancer treated with ribociclib plus endocrine therapy: results from a phase III randomized clinical trial (MONALEESA-7).

Publications

Health-related quality of life in premenopausal women with hormone-receptor-positive, HER2-negative advanced breast cancer treated with ribociclib plus endocrine therapy: results from a phase III randomized clinical trial (MONALEESA-7).

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