Health-related quality of life of patients with resistant/intolerant chronic phase chronic myeloid leukemia treated with asciminib or bosutinib in the phase 3 ASCEMBL trial.

In ASCEMBL, an open-label, randomized Phase 3 study, asciminib demonstrated superior efficacy and better safety profile compared with bosutinib in patients with chronic myeloid leukemia in chronic phase (CML-CP) previously treated with ≥2 tyrosine kinase inhibitors. Health-related quality of life (HRQOL) reported by patients is key to understanding the benefit and impact of treatment on patients' lives, and is becoming increasingly important as the life expectancy of CML-CP patients increases and patients require long-term treatment. In ASCEMBL, patients completed questionnaires to assess CML symptoms and interference with daily life (M.D. Anderson Symptom Inventory - CML [MDASI-CML]), general HRQOL (five-level EQ-5D [EQ-5D-5L], Patient Global Impression of Change - CML [PGIC-CML]), and impact of CML on working life and activity (Work Productivity and Activity Impairment questionnaire - CML [WPAI-CML]). Patients' CML symptoms and HRQOL remained stable during 48 weeks of treatment with asciminib, with a general trend for decreased CML symptom severity, particularly for fatigue, and improvement in HRQOL. A clinically meaningful increase in diarrhea severity was observed in patients treated with bosutinib compared to asciminib. These data provide better understanding of the patient perspective and treatment impact on HRQOL in a later-line setting, where little information has been published to date.

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

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).

Matching-adjusted indirect comparison of asciminib versus other treatments in chronic-phase chronic myeloid leukemia after failure of two prior tyrosine kinase inhibitors.

PURPOSE: The current standard of care for chronic-phase chronic myeloid leukemia (CP-CML) is tyrosine kinase inhibitors (TKIs). Treatment recommendations are unclear for CP-CML failing ≥ 2 lines of treatment, partly due to the paucity of head-to-head trials evaluating TKIs. Thus, matching-adjusted indirect comparisons (MAICs) were conducted to compare asciminib with competing TKIs in third- or later line (≥ 3L) CP-CML. METHODS: Individual patient-level data for asciminib (ASCEMBL; follow-up: ≥ 48 weeks) and published aggregate data for comparator TKIs (ponatinib, nilotinib, and dasatinib) informed the analyses. Major molecular response (MMR), complete cytogenetic response (CCyR), and time to treatment discontinuation (TTD) were assessed, where feasible. RESULTS: Asciminib was associated with statistically significant improvements in MMR by 6 (relative risk [RR]: 1.55; 95% confidence interval [CI]: 1.02, 2.36) and 12 months (RR: 1.48; 95% CI: 1.03, 2.14) vs ponatinib. For CCyR, the results vs ponatinib were similar by 6 (RR: 1.11; 95% CI: 0.81, 1.52) and 12 months (RR: 0.97; 95% CI: 0.73, 1.28). Asciminib was associated with improvements in MMR by 6 months vs dasatinib but with a CI overlapping one (RR 1.52; 95% CI: 0.66, 3.53). Asciminib was associated with statistically significant improvements in CCyR by 6 (RR: 3.57; 95% CI: 1.42, 8.98) and 12 months (RR: 2.03; 95% CI: 1.12, 3.67) vs nilotinib/dasatinib. Median TTD was unreached for asciminib in ASCEMBL. However, post-adjustment asciminib implied prolonged TTD vs nilotinib and dasatinib, but not vs ponatinib. CONCLUSION: These analyses demonstrate favorable outcomes with asciminib versus competing TKIs, highlighting its therapeutic potential in ≥ 3L CP-CML.

Enabling access to molecular monitoring for chronic myeloid leukemia patients is cost effective in China.

OBJECTIVE: To determine the cost effectiveness of molecular monitoring in patients with chronic myeloid leukemia in the chronic phase (CML-CP) compared to no molecular monitoring from a Chinese payer perspective. METHODS: Analyses were conducted using a semi-Markov model with a 50-year time horizon. Population data from multicenter registry-based studies of Chinese patients with CML-CP informed the model. Transition probabilities were based on time-to-event data from the literature. Utility values were obtained from published studies and were assumed to be the same for patients with and without molecular monitoring. Costs were based on values commonly used in the Chinese healthcare system, including drug acquisition, drug administration, follow-up, treatment for disease progression, molecular monitoring, and terminal care costs, and were in the local currency (2020 Chinese Yuan RMB [¥]). Outcomes were total life-years (LYs) and quality-adjusted life years (QALYs), lifetime costs, and incremental cost-effectiveness ratio. RESULTS: Molecular monitoring was dominant to no molecular monitoring, with increased LYs (1.52) and QALYs (1.90) and costs savings (¥93,840) over a lifetime compared to no monitoring in discounted analyses. The opportunity of patients that receive molecular monitoring to discontinue treatment during treatment-free remission, an opportunity not afforded to those without molecular monitoring, was the principle driver of this result. Results were similar across multiple clinical scenarios. Particularly, molecular monitoring remained dominant even if the proportion of patients achieving deep molecular response (DMR) was reduced by 10%-30%, or the proportion of patients maintaining DMR for 1 year was reduced by 10%-30% or increased by 10%. Cost savings in these scenarios ranged from ¥62,230 to ¥103,964. CONCLUSIONS: Overall, this analysis demonstrates that adherence to guideline recommendations of regular molecular monitoring of patients with CML-CP treated with TKIs provides significant clinical benefit that leads to substantial cost savings compared to no molecular monitoring from the perspective of a Chinese payer. In a time where healthcare systems have limited resources to allocate to optimal patient care, investment in molecular monitoring is an ideal choice for improving patient benefits at a reduced cost.