Health Economics
Combined Chemoradiation Cost-Effective in Younger Patients with Primary CNS Lymphoma Chemotherapy alone favored in older patients
See also Lymphoma
By Wayne Kuznar
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cost-effective analysis shows that combined-modality therapy (CMT) is the preferred induction strategy over chemotherapy alone for younger patients with primary central nervous system (CNS) lymphoma. “This strategy minimizes cost, while maximizing life expectancy and quality-adjusted life-years,” said lead investigator Anca Prica, MD, a hematology/oncology fellow at Sunnybrook Health Sciences Centre, Toronto, Canada. Meanwhile, the preferred strategy for older patients is chemotherapy alone, Dr Prica said. CMT using high-dose methotrexate and whole-brain radiotherapy is associated with improved response rates and a decrease in relapse rates compared with chemotherapy alone. The trade-off is a significant risk of delayed, treatment-related neurotoxicity, leading to significant morbidity and mortality. The rate of late neurotoxicity with CMT ranges from 26% to 100%, she said, with the risk of neurotoxicity being greater in older patients compared with those aged <60 years. Dr Prica and her group performed a
cost-effectiveness analysis comparing the 2 strategies, stratifying the analysis by age. The quality-adjusted life-year (QALY) and incremental cost-effectiveness ratio (ICER) were compared between the 2 strategies.
“This strategy [CMT] minimizes cost, while maximizing life expectancy and quality-adjusted life-years.” —Anca Prica, MD A Markov decision analytic model was used to compare CMT and chemotherapy alone for a hypothetical cohort of 60-year-old patients who were newly diagnosed with primary CNS lymphoma. Cohorts of patients aged <60 years and >60 years were analyzed. The model simulated the clinical course of patients over the course of 5 years. The variables included response, relapse, and survival rates with CMT versus chemotherapy alone; the risk of developing neurotoxicity with each
strategy; and the estimated survival once neurotoxicity develops. The model incorporated data on health state utilities, which were derived from a survey of expert physicians who manage patients with primary CNS lymphoma. Resource utilization was based on clinical guidelines, the literature, and expert opinion. The direct costs were obtained from hospital, provincial, and national sources, as well as the literature, and were calculated in 2011 Canadian dollars. The indirect costs were estimated based on lost productivity using average wages in Canada. The costs and the effects were discounted by 5%. All patients who received chemotherapy alone as induction therapy were assumed to have whole-brain radiotherapy on disease relapse. The benefit of having active disease was assumed to dominate any ill effects from neurotoxicity. The cost of living with neurotoxicity was assumed to be similar to living with Alzheimer’s dementia. The quality-adjusted life expectancy was 1.55 QALYs for CMT versus 1.53 QALYs for chemotherapy alone.
The ICER for the base-case CMT versus chemotherapy alone was $491,522 per life-year gained. In patients aged <60 years, CMT yielded 2.44 QALYs compared with 1.89 QALYs for chemotherapy alone, corresponding to an expected benefit of 0.55 QALYs with CMT, or 6.6 quality-adjusted months. The CMT strategy dominated in younger patients, being $11,951 less expensive than chemotherapy alone. There was no difference in QALYs between the strategies in patients aged >60 years. The chemotherapyalone strategy dominated in the older group—it cost $11,244 less than CMT. For younger patients, there were no threshold values for the cost of CMT or for the cost of managing severe neurotoxicity that would potentially lead to chemotherapy alone being favored, said Dr Prica. The model favored treating younger patients with CMT, unless the rate of neurotoxicity was more than 89% at 1 year, “a rate not encountered in the published literature.” Similarly, there were no circumstances under which CMT was favored for older patients. n
Azacitidine Reduces Transfusions and Costs for Patients... Continued from page 1 Transfusion dependence in patients with MDS is associated with greater health resource utilization and high transfusion-related costs in the inpatient and the outpatient settings. It is also associated with increased mortality, Dr Tseng said. “Hypomethylating agents, including azacitidine, have been shown to be cost-effective in treating high-risk MDS,” he said, “but there is a lack of studies assessing the effect of azacitidine on transfusion requirements and transfusion-related costs in the realworld clinical setting.” Using real-world data, Dr Tseng and colleagues retrospectively re viewed data of 51 patients with MDS who were treated with the approved dose and schedule of azacitidine at their tertiary care center between 2008 and 2012. The cost per unit of RBCs was $1183 (2008 US dollars) and $1273 (2012 Canadian dollars). Transfusion costs per patient were determined for VOL. 6
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6-month intervals before and after the initiation of azacitidine. Substantial Decline in Transfusions and Costs “The number of units transfused decreased in both the inpatient and outpatient settings after treatment with azacitidine was initiated,” Dr Tseng added. The number of RBC transfusions and costs declined sub stantially between baseline and 12month to 18-month follow-up (shown in Canadian dollars): • 6 months before azacitidine: 11 RBC units transfused; cost, $14,048 • 0 to 6 months after azacitidine: 10.9 RBC units; cost, $13,898 • 6 to 12 months after azacitidine: 8.2 RBC units; cost, $10,407 • 12 to 18 months after azacitidine: 6.9 RBC units; cost, $8744. The patients in this study had similar response rates with azacitidine as those in the AZA001 trial, which
at a glance ➤ Hypomethylating agents are cost-effective for high-risk MDS, but real-world data are lacking ➤ Based on real-world clinical data, azacitidine reduces the need for RBC transfusion and transfusion dependence in patients with high-risk MDS ➤ Azacitidine reduced RBC transfusion costs per patient by 26% at 12 months and by 38% by 18 months ➤ Reduced utilization was seen in the inpatient and outpatient settings ➤ Overall, 63% of the patients became transfusion independent within 18 months of starting azacitidine therapy
were robust in approximately 66% of patients. The median number of cycles was 11, and the median time to best response was 6 months.
“At 12 and 18 months after azacitidine treatment, there were 26% and 38% reductions in RBC transfusion costs, respectively, per patient compared with the 6 months before therapy.” —Eric Tseng, MD Overall, 63% became transfusion independent within 18 months of the initiation of azacitidine. Median time to transfusion independence was 3 months, Dr Tseng reported. n
february 2013
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