Quality of life with ribociclib versus abemaciclib as first-line treatment of HR+/HER2− advanced breast cancer: a matching-adjusted indirect comparison

Abstract

Background: A cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) + endocrine therapy is recommended as first-line treatment for hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2−) advanced breast cancer (ABC). Quality of life (QoL) is an important endpoint that affects treatment decisions. Understanding the relevance of CDK4/6i treatment on QoL is gaining importance given use in earlier treatment lines for ABC and an emerging role in treating early breast cancer in which QoL may be more impactful. In the absence of head-to-head trial data, a matching-adjusted indirect comparison (MAIC) permits comparative efficacy between trials. Objective: In this analysis, patient-reported QoL for MONALEESA-2 [ribociclib + aromatase inhibitor (AI)] and MONARCH 3 (abemaciclib + AI) was compared using MAIC with a focus on individual domains. Design: An anchored MAIC of QoL comparing ribociclib + AI versus abemaciclib + AI was performed using data from the European Organization for Research and Treatment of Cancer quality of life questionnaire (QLQ)-C30 and BR-23 questionnaires. Methods: Individual patient data from MONALEESA-2 and published aggregated data from MONARCH 3 were included in this analysis. Time to sustained deterioration (TTSD) was calculated as the time from randomization to a ⩾10-point deterioration with no later improvement above this threshold. Results: Patients from the ribociclib ( n = 205) and placebo ( n = 149) arms of MONALEESA-2 were matched with patients from the abemaciclib ( n = 328) and placebo ( n = 165) arms of MONARCH 3. After weighting, baseline patient characteristics were well balanced. TTSD significantly favored ribociclib versus abemaciclib in appetite loss [hazard ratio (HR), 0.46; 95% confidence interval (CI), 0.27–0.81], diarrhea (HR, 0.42; 95% CI, 0.23–0.79), fatigue (HR, 0.63; 95% CI, 0.41–0.96), and arm symptoms (HR, 0.49; 95% CI, 0.30–0.79). TTSD did not significantly favor abemaciclib compared with ribociclib in any functional or symptom scale of the QLQ-C30 or BR-23 questionnaires. Conclusions: This MAIC indicates that ribociclib + AI is associated with better symptom-related QoL than abemaciclib + AI for postmenopausal patients with HR+/HER2− ABC treated in the first-line setting. Trial registration: NCT01958021 (MONALEESA-2) and NCT02246621 (MONARCH 3)

Cyclin-dependent kinase 4/6 inhibitors in the treatment of advanced or metastatic breast cancer

“…Abemaciclib is associated with a clinically manageable safety profile, which facilitates continuous dosing and reduced myelosuppression. 29–31 The most common treatment-emergent adverse events (TEAEs) coinciding with abemaciclib include diarrhea, neutropenia, infection, and fatigue. 19 Dose reductions were reported in approximately 43% of patients in the MONARCH-2 and MONARCH-3 studies; nevertheless, dose reductions were ostensibly effective at mitigating the incidence (25.1%) of treatment-related discontinuations.…”

Loss of appetite in patients with cancer: an update on characterization, mechanisms, and palliative therapeutics

“…Upon visual inspection of graphical data, a more than four times worsening of symptoms occurred with the addition of palbociclib, an observation that suggests anorexia can be caused not only from the cancer itself and not only from conventional chemotherapy but also from newer agents such as palbociclib 3 . Of note, comparative data from a trial that tested ribociclib versus abemaciclib – two other CD4/6 inhibitors – suggest that the former might lead to less appetite loss, as assessed by time to sustained deterioration 4 . This study yielded a hazard ratio of 0.46 (95% confidence interval 0.27–0.81), in favor of less anorexia with ribociclib 4 .…”

“…Of note, comparative data from a trial that tested ribociclib versus abemaciclib – two other CD4/6 inhibitors – suggest that the former might lead to less appetite loss, as assessed by time to sustained deterioration 4 . This study yielded a hazard ratio of 0.46 (95% confidence interval 0.27–0.81), in favor of less anorexia with ribociclib 4 . Although a patient’s cancer status will likely dictate which CDK4/6 inhibitor should be used when, the above findings might be of value as clinicians make drug choices for specific patients who have metastatic cancer and who are already suffering from anorexia.…”

Matching-adjusted indirect comparison of PFS and OS comparing ribociclib plus letrozole versus palbociclib plus letrozole as first-line treatment of HR+/HER2− advanced breast cancer

“…11 MAIC has been widely used to compare a range of outcomes from phase III clinical trials where no head-to-head study has been available, including among CDK4/6is. [12][13][14][15] In addition, MAIC has been accepted by several national health technology assessment agencies to help inform decision-making. 11,16 In this study, an MAIC was performed to compare both PFS and OS with first-line ribociclib + letrozole versus palbociclib + letrozole using data from the MONALEESA-2 and PALOMA-2 trials.…”

“…11 MAIC has been widely used to compare a range of outcomes from phase III clinical trials where no head-to-head study has been available, including among CDK4/6is. 12–15 In addition, MAIC has been accepted by several national health technology assessment agencies to help inform decision-making. 11,16…”