Rising drug cost impacts on cost-effectiveness of 2 chemotherapy regimens for intermediate-risk rhabdomyosarcoma: A report from the Children's Oncology Group.

BACKGROUND: The Children's Oncology Group clinical trial for intermediate risk rhabdomyosarcoma randomized participants to a combination of vincristine, dactinomycin, and cyclophosphamide (VAC) alone or VAC alternating with vincristine plus irinotecan (VAC/VI). Clinical outcomes were similar, but toxicity profiles differed. This study estimates the cost differences between arms from the health care system's perspective. METHODS: A decision-analytic model was used to estimate the incremental cost-effectiveness ratio (ICER) of VAC versus VAC/VI. Protocol-required or recommended medications and laboratory studies were included. Costs were obtained from national databases or supporting literature and inflated to 2019 US dollars. Demographic and outcome data were obtained from the clinical trial and directed chart reviews. Life-years (LY) were estimated from life-expectancy tables and discounted by 3% annually. Probabilistic sensitivity analyses and alternative clinical scenarios identified factors driving costs. RESULTS: Mean direct medical costs of VAC and VAC/VI were $164,757 and $102,303, respectively. VAC was associated with an additional 0.97 LY and an ICER of $64,386/LY compared with VAC/VI. The ICER was sensitive to survival estimations and to alternative clinical scenarios including outpatient cyclophosphamide delivery (ICER $49,037/LY) or substitution of alternative hematopoietic growth factor schedules (ICER $73,191-$91,579/LY). Applying drug prices from 2012 decreased the total costs of VAC by 20% and VAC/VI by 15% because of changes in dactinomycin and pegfilgrastim prices. CONCLUSIONS: Neither arm was clearly more cost-effective. Pharmaceutical pricing and location of treatment drove costs and may inform future treatment decisions. Rising pharmaceutical costs added $30,000 per patient, a finding important for future drug-pricing policy decisions. LAY SUMMARY: Two chemotherapy regimens recently tested side-by-side for rhabdomyosarcoma had similar tumor outcomes, but different side effects. The health care costs of each regimen were compared; neither was clearly more cost-effective. However, the costs of each treatment changed dramatically with choices of supportive medicines and location of treatment. Costs of treatment rose by 15% to 20% because of rising US drug costs not associated with the clinical trial.

Comparison of pulsed actinomycin D and 5-day actinomycin D as first-line chemotherapy for low-risk gestational trophoblastic neoplasia.

OBJECTIVE: To compare the treatment outcome and cost-effectiveness of pulsed actinomycin D (Act-D) and 5-day Act-D in patients with low-risk gestational trophoblastic neoplasia (GTN). METHOD: The present retrospective study included patients with low-risk GTN who received pulsed Act-D or 5-day Act-D as first-line chemotherapy at West China Second Hospital, Chengdu, China, between January 1, 2016, and December 31, 2017. Complete remission rates, mean number of treatment courses, and adverse events were compared, and a cost-effectiveness analysis was performed. RESULTS: The study included 34 patients treated with pulsed Act-D and 26 patients treated with 5-day Act-D. Overall complete remission was observed in 21 (62%) patients in the pulsed Act-D group and 19 (73%) patients in the 5-day Act-D group (P=0.355); the mean number of treatment courses were 5.1 and 5.3, respectively (P=0.686). When Act-D failed, patients in each group required 4.9 and 4.6 courses, respectively, of a multi-agent regimen (P=0.545). No major adverse events were observed but moderate adverse events were more frequent in the pulsed Act-D group (P=0.011). The 5-day Act-D regimen was more expensive compared with pulsed Act-D regimen (US$7504.33 vs $5541.79), with an incremental cost-effectiveness ratio of $64 557.08 per avoidance of treatment failure. CONCLUSION: Pulsed Act-D was more cost-effective than 5-day Act-D and could be preferred when considering Act-D as chemotherapy for low-risk GTN.

Are different methotrexate regimens as first line therapy for low risk gestational trophoblastic neoplasia more cost effective than the dactinomycin regimen used in GOG 0174?

OBJECTIVES: Gynecologic Oncology Group (GOG) 0174 compared weekly intramuscular methotrexate (MTX) with biweekly pulsed intravenous dactinomycin (Act-D) as single-agent chemotherapy for low-risk gestational trophoblastic neoplasia (GTN). Act-D had a higher rate of initial complete response (CR) (70% vs. 53%, p=0.01), but multi-day regimens of MTX have higher historic success rates. We assessed the cost-effectiveness of Act-D vs. MTX per GOG 0174 and explored multi-day MTX regimens. METHODS: A cost effectiveness decision model was constructed with data from GOG 0174. Outcome was cost per first-line treatment success expressed in terms of incremental cost-effectiveness ratio (ICER). Front-line failures were assumed to receive cross-over single agent therapy, second line failures; multi-agent chemotherapy. GOG 0174 had no quality of life (QOL) evaluation, so equal QOL (utility 1.0) was assumed but varied in sensitivity analysis. A second exploratory model included 5-day and 8-day MTX regimens. RESULTS: Act-D ($18,505) was more expensive compared to weekly MTX ($8950) with an ICER of $56,215 per first-line treatment success compared to weekly MTX. Small decreases in QOL dramatically increased the ICER during sensitivity analysis. Models with multi-day MTX regimens were also more cost-effective than Act-D. If effectiveness was redefined as avoidance of multi-agent chemotherapy, weekly MTX was more effective. CONCLUSIONS: With a complete cure rate for low-risk GTN regardless of initial agent, our model supports provider hesitation toward first line Act-D for low risk GTN. While Act-D is more effective for first line treatment success, it is more costly, and does not decrease rate of multi-agent chemotherapy use.

Comparison of Cost-Effectiveness Between Actinomycin D Versus Methotrexate-Folinic Acid in the Treatment of Low-Risk Gestational Trophoblastic Neoplasia.

OBJECTIVE: To compare the cost-effectiveness between actinomycin D (Act-D) and methotrexate-folinic acid (MTX-FA) in the treatment of low-risk gestational trophoblastic neoplasia (GTN) in the Thai population. STUDY DESIGN: A comparative cost-effectiveness analysis was performed from a societal perspective. A decision tree model was developed comparing 2 alternative treatment options: initial 5-day Act-D and 8-day MTX-FA. Treatment would be switched to another regimen in case of resistance. The outcome of interest is number of days to remission. Clinical data was obtained from our previous study in which Act-D demonstrated 100% remission rates as compared to 73.6% for MTX-FA. Cost of treatment data, which includes chemotherapeutics, accessory medications, laboratory tests, and hospital fees, was obtained from a university hospital. Patient-related travel cost and opportunity cost due to absence from work were also included. All costs were calculated to 2015 base year. RESULT: Costs per treatment cycle were $308.01 and $227.20 US dollars (USD) for 5-day Act-D and 8-day MTX-FA, respectively. Expected time toward treatment completion for Act-D was 12.6 days shorter than for MTX-FA. Expected costs toward remission for initial treatment with Act-D and MTX-FA were $1,078.04 and $1,064.56 USD, respectively, i.e., an incremental cost effectiveness ratio (ICER) of $1.07 USD/day of earlier treatment completion. After sensitivity analysis, remission rate of lower than 72% would make initial treatment with MTX-FA more expensive than with Act-D. CONCLUSION: Treatment costs of low-risk GTN are almost equal between the 2 treatment options with different time to remission. Initial treatment with MTX-FA is slightly less expensive, but there is longer time to remission. The ICER of initial treatment with Act-D over MTX-FA is $1.07 USD/day of earlier treatment completion.

Inpatient versus outpatient vincristine, dactinomycin, and cyclophosphamide for pediatric cancers: Quality and cost implications.

BACKGROUND: Approximately 18% of the United States' gross domestic product is attributed to healthcare expenditures. Several studies have illustrated that shifting healthcare from the inpatient to the outpatient setting is more cost effective, in addition to improving patient satisfaction. Vincristine, dactinomycin, and cyclophosphamide (VAC) are used together to treat children with solid tumors. Our traditional treatment approach included a two day inpatient admission. The purpose of this project was to establish a process for the administration of VAC in the outpatient setting to improve satisfaction, and reduce costs. PROCEDURE: We aimed to benchmark practice standards with other institutions, revised our treatment approach to permit outpatient administration, and implemented the new protocol in a stepwise manner. We collected caregiver satisfaction metrics through the use of surveys. Costs of encounters were obtained from administrative data. Total costs and costs by service type were compared using descriptive and mean comparisons. RESULTS: Seven patients received a total of 31 cycles of VAC in the outpatient setting. The time to achieve an appropriate pre-chemotherapy specific gravity was reduced by a median of 120 min. In addition, time spent in the hospital setting was reduced by a mean of 27.2 hr. Adverse effects were minimal and all caregivers reported greater satisfaction with the outpatient regimen. Outpatient administration of VAC was $3,300 less on average compared to the inpatient administration. CONCLUSION: Outpatient VAC provides a safe alternative for administration that reduces healthcare costs, reduces healthcare utilization, and improves patient satisfaction.