Impact of venetoclax monotherapy on the quality of life of patients with relapsed or refractory chronic lymphocytic leukemia: results from the phase 3b VENICE II trial.

Venetoclax, a potent B-cell lymphoma-2 (BCL-2) inhibitor, has demonstrated clinical efficacy in chronic lymphocytic leukemia (CLL). VENICE II is an open-label, single-arm, phase 3b study (NCT02980731) evaluating the impact of venetoclax monotherapy (400 mg once daily) for ≤2 years on health-related quality of life (HRQoL) of patients with relapsed/refractory CLL. The primary endpoint was mean change in the global health status (GHS)/quality of life (QoL) subscale of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) from baseline to Week 48. Overall, 210 patients received ≥1 dose of venetoclax; median treatment duration was 67.4 weeks. The primary endpoint was met with mean improvement of +9.3 points (n = 156, 95% confidence interval 6.1-12.5; p=.004) in GHS/QoL. At Week 48, clinically meaningful improvements were observed for role functioning, fatigue, and insomnia domains of EORTC QLQ-C30, suggesting venetoclax monotherapy has a positive impact on HRQoL. No new safety signals were reported.

Budget Impact of 12-Month Fixed Treatment Duration Venetoclax in Combination with Obinutuzumab in Previously Untreated Chronic Lymphocytic Leukemia Patients in the United States.

OBJECTIVES: This study aimed to assess the total cost of care (TCC) and budget impact of introducing 12-month fixed duration venetoclax + obinutuzumab (VEN+G) as first-line treatment for chronic lymphocytic leukemia (CLL) from the perspective of a US health plan with 1,000,000 (1M) members. METHODS: The 3-year model included the following comparators: fludarabine + cyclophosphamide + rituximab (FCR), bendamustine + rituximab (BR), obinutuzumab + chlorambucil (GClb), ibrutinib (Ibr), and Ibr+Rituximab/obinutuzumab [Ibr+R/Ibr+G]). TCC included US-specific costs associated with treatment (i.e., drug, administration, and wastage), adverse events, routine care, and monitoring. Dosing and safety data were drawn from clinical trials and US package inserts. Budget impact outcomes were presented on an absolute and per-member per-month (PMPM) basis. Sensitivity analyses explored uncertainty in influential parameters, including scenarios testing the duration of treat-to-progression agents. RESULTS: Over the 3-year time horizon, introducing VEN+G in a 1M-member health plan resulted in total cost savings of $1,550,663 (PMPM - $0.04), compared to a scenario without VEN+G. The fixed 12-month duration of VEN+G contributed to this cost saving by reducing cumulative treatment costs compared with Ibr-based regimens. By year 3, the cumulative difference in TCC of VEN+G compared with Ibr, Ibr+G, and Ibr+R amounted to - $300,942, - $367,001, and - $369,784, respectively. Extensive sensitivity analyses supported the base case findings. CONCLUSIONS: Introducing VEN+G among first-line CLL treatments to a US health plan resulted in cost savings compared to a plan with chemoimmunotherapies and Ibr-based therapies only. Economic benefits of VEN+G, a novel agent with fixed treatment duration, coupled with proven clinical benefits should help inform formulary adoption decisions and treatment recommendations.

Assessment of treatment and monitoring patterns and subsequent outcomes among patients with chronic myeloid leukemia treated with imatinib in a community setting.

INTRODUCTION: Real-world treatment and monitoring patterns have not been well documented among imatinib-treated chronic phase chronic myeloid leukemia (CP-CML) patients. Thus, we evaluated these patterns and responses to imatinib in CP-CML patients. METHODS: This retrospective study, based on the Georgia Cancer Specialists' electronic medical record (EMR) system, identified CP-CML patients initiating treatment with imatinib from 01/01/2002 to 11/01/2011 who were subsequently followed for ≥6 months. RESULTS: A total of 177 patients met the study criteria. Imatinib dose modification occurred in 59 patients (33%). Rates of treatment interruption, discontinuation, and switching to another therapy were 16%, 24%, and 23%, respectively. Of 27 patients discontinuing imatinib for lack of efficacy, 9 (33%) had initial dose escalation; 26 patients (96%) eventually switched to a second-generation tyrosine kinase inhibitor. By 3 months, 168 patients remained on imatinib, of whom 96 (57%) had undergone cytogenetic and/or molecular testing. The frequency of response monitoring fluctuated over time, with rates as high as 28% for cytogenetic and 69% for molecular testing. Cumulative response rates steadily increased; 18 month rates were 47% for complete cytogenetic response and 26% for major or complete molecular response. There were no cases of progression and/or death among 38 patients who were regularly monitored for molecular response within the first 12 months of imatinib. Ten of 98 patients (10%) not regularly monitored had progressed or died. CONCLUSIONS: Almost one-third of patients initiating imatinib for CP-CML required dose modification, treatment interruption, or discontinuation. Opportunities for improved monitoring in this setting were identified. Limitations include those inherent to retrospective analyses based on EMR and the uncertain extrapolability of the results.

Clinical and economic outcomes associated with adjuvant chemotherapy in elderly patients with early stage operable breast cancer.

OBJECTIVES: Breast cancer poses a huge medical burden to the U.S. health-care system, and chemotherapy is an important contributor to cancer costs. This article examines the differences between breast cancer patients who received chemotherapy and those who did not in costs and survival by age, treatment, and axillary node status. METHODS: We studied a cohort of 23,110 node-positive and 31,572 node-negative women aged 65 years and older diagnosed with incident American Joint Committee on Cancer stage I, II, or IIIA breast cancer between January 1, 1991, and December 31, 2002, using Surveillance Epidemiology and End Results-Medicare data. Total treatment costs and costs associated with the use of chemotherapy were estimated by using the phase-of-care approach. The phase-specific costs were combined to estimate total Medicare payments for cancer care from diagnosis to death. Cox proportional hazard ratio of mortality was used to determine the effectiveness of adjuvant chemotherapy after adjusting for selected patient and tumor characteristics. We used propensity scores to minimize the bias associated with the receipt of adjuvant chemotherapy. RESULTS: Regression-adjusted difference in the average lifetime cost estimates for all node-positive patients receiving chemotherapy was approximately $2438 and was significantly higher (P < 0.05) than for patients not receiving chemotherapy. Mortality was significantly lower in node-positive and node-negative women aged 65 to 74 years receiving chemotherapy. CONCLUSIONS: Decision makers can use cost and effectiveness estimates from this study to assess the relative value of chemotherapy in different age groups.