Cost Effectiveness of Ribociclib in Combination with Fulvestrant for the Treatment of Postmenopausal Women with HR+/HER2- Advanced Breast Cancer Who Have Received No or Only One Prior Line of Endocrine Therapy: A Canadian Healthcare Perspective.

BACKGROUND: The MONALEESA-3 trial demonstrated the efficacy and safety of ribociclib plus fulvestrant versus placebo plus fulvestrant for patients with hormone receptor-positive and human epidermal growth factor receptor 2-negative (HR+/HER2-) advanced breast cancer (ABC). This analysis evaluated the cost effectiveness of ribociclib plus fulvestrant versus fulvestrant in patients with HR+/HER2- ABC from a Canadian healthcare payer perspective. METHODS: The incremental cost-effectiveness ratio (ICER), expressed as incremental costs per quality-adjusted life-year (QALY) gained for ribociclib plus fulvestrant versus fulvestrant, was estimated using a semi-Markov cohort model developed in Microsoft Excel, with states for progression-free, post-progression, and dead. A 15-year time horizon was used. Survival distributions for progression-free survival (PFS), post-progression survival (PPS), and time to discontinuation (TTD) were based on parametric survival distributions fit to data from MONALEESA-3. Health-state utilities were estimated using EQ-5D index values collected in MONALEESA-3. Direct costs of ABC treatment (medication and administration costs, follow-up and monitoring, adverse events, subsequent treatments) were based on Canadian-specific values from published sources. Costs (2019 CAN$) and QALYs were discounted at 1.5% annually. RESULTS: In the base case, ribociclib plus fulvestrant was estimated to result in gains of 1.19 life-years and 0.96 QALYs versus fulvestrant, at an incremental cost of $151,371. The ICER of ribociclib plus fulvestrant versus fulvestrant was $157,343 per QALY gained based on the mean of probabilistic analyses. Results were sensitive to parametric distributions used for projecting long-term TTD, PFS, and PPS. CONCLUSIONS: For patients with HR+/HER2- ABC, ribociclib plus fulvestrant is projected to result in substantial gains in QALYs compared with fulvestrant. At its current list price, ribociclib used in combination with fulvestrant is likely to be cost effective in these patients at a threshold ICER of $157,343. These results may be useful in deliberations regarding reimbursement and access to this treatment.

Cost Effectiveness of Ribociclib Plus a Nonsteroidal Aromatase Inhibitor in Pre-/Perimenopausal, HR+ and HER2- Advanced Breast Cancer: A Canadian Healthcare Perspective.

BACKGROUND AND OBJECTIVES: The MONALEESA-7 trial demonstrated the efficacy and safety of ribociclib plus a nonsteroidal aromatase inhibitor (NSAI) [with goserelin] for pre-/perimenopausal women with hormone receptor-positive and human epidermal growth factor receptor 2-negative advanced breast cancer. This analysis evaluated the cost effectiveness of ribociclib plus NSAI vs NSAI monotherapy and tamoxifen monotherapy from the perspective of the Canadian healthcare system. METHODS: The incremental cost-effectiveness ratio expressed as incremental costs per quality-adjusted life-year (QALY) gained for ribociclib plus an NSAI vs an NSAI and vs tamoxifen was estimated using a semi-Markov cohort model developed in Microsoft Excel with a 15-year time horizon and states for progression-free survival, post-progression survival, and dead. Survival distributions for progression-free survival, post-progression survival, and time to discontinuation as well as health-state utilities were estimated using data from MONALEESA-7. Direct costs of advanced breast cancer treatment were based on Canadian-specific values from published sources. Costs ($CAN 2019) and QALYs were discounted at 1.5% annually. RESULTS: Ribociclib plus an NSAI was estimated to yield gains of 1.42 life-years and 1.17 QALYs vs an NSAI, and 2.61 life-years and 2.12 QALYs vs tamoxifen, at incremental costs of $209,701 and $220,836, respectively. In probabilistic analyses, the incremental cost-effectiveness ratio for ribociclib plus an NSAI was estimated to be $178,872 per QALY gained vs an NSAI and $104,400 per QALY gained vs tamoxifen. Results of deterministic analyses were similar (incremental cost-effectiveness ratios of $177,245 and $103,316 vs NSAI and tamoxifen, respectively). Results were sensitive to parametric distributions used for projecting progression-free survival and the time horizon. CONCLUSIONS: At its current list price, ribociclib used in combination with NSAI is likely to be co-effective relative to an NSAI alone or tamoxifen alone if the willingness-to-pay threshold is less than approximately $178,000 per QALY. These results have informed deliberations regarding reimbursement and access to this treatment in Canada and may be useful for decision makers in other settings.

Preferences of Canadian Patients and Physicians for Treatment of HR+/HER2- Advanced Breast Cancer.

(1) Background: Past research suggests that patients with advanced breast cancer prefer treatments with improved clinical outcomes and lower risk of side effects. Evidence on preferences of Canadian patients and physicians for treatments for advanced breast cancer is limited. (2) Methods: Patients' and physicians' preferences for treatments for HR+/HER2-, pre-/peri-menopausal advanced breast cancer were assessed by an online discrete choice experiment (DCE). Treatment alternatives were characterized by seven attributes regarding dosing, efficacy, and toxicities, with levels corresponding to those for ribociclib plus a non-steroidal aromatase inhibitor (NSAI), NSAI, and tamoxifen. For patients, impacts of advanced breast cancer on quality of life (QOL) and ability to work/perform activities of daily living also were assessed. Patients were recruited by a Canadian breast cancer patient advocacy group through email and social media. Physicians were recruited by email. (3) Results: Among 118 patients starting the survey, 23 completed ≥ 1 DCE question (19%). Among 271 physicians who were sent the e-mail invitation, 21 completed ≥ 1 DCE question (8%). For both patients and physicians, the increased probability of remaining alive and without cancer progression over 2 years was the most important attribute. A treatment with attributes consistent with ribociclib plus NSAI was chosen by patients and physicians in 70% and 88% of the time, respectively. A substantial proportion of patients reported worrying about future diagnostic tests and their cancer getting worse; (4) Conclusions: Canadian patients and physicians are generally concordant in preference for advanced breast cancer treatments, preferring ribociclib plus NSAI to other options.

Budget Impact of Dabrafenib and Trametinib in Combination as Adjuvant Treatment of BRAF V600E/K Mutation-Positive Melanoma from a U.S. Commercial Payer Perspective.

BACKGROUND: Before the approval of dabrafenib and trametinib in combination, there were no approved therapies in the adjuvant setting that target the RAS/RAF/MEK/ERK pathway. OBJECTIVE: To evaluate the budget impact of dabrafenib and trametinib in combination for adjuvant treatment of patients with BRAF V600 mutation-positive resected Stage IIIA, IIIB, or IIIC melanoma from a U.S. commercial payer perspective using data from the COMBI-AD trial, as well as other sources. METHODS: The budget impact of dabrafenib and trametinib in combination for patients with BRAF V600E/K mutation-positive, resected Stage IIIA, IIIB, or IIIC melanoma was evaluated from the perspective of a hypothetical population of 1 million members with demographic characteristics consistent with those of a commercially insured U.S. insurance plan (i.e., adults aged less than 65 years) using an economic model developed in Microsoft Excel. The model compared melanoma-related health care costs over a 3-year projection period under 2 scenarios: (1) a reference scenario in which dabrafenib and trametinib are assumed to be unavailable for adjuvant therapy and (2) a new scenario in which the combination is assumed to be available. Treatments potentially displaced by dabrafenib and trametinib were assumed to include observation, high-dose interferon alpha-2b, ipilimumab, and nivolumab. Costs considered in the model include those of adjuvant therapies and treatment of locoregional and distant recurrences. The numbers of patients eligible for treatment with dabrafenib and trametinib were based on data from cancer registries, published sources, and assumptions. Treatment mixes under the reference and new scenarios were based on market research data, clinical expert opinion, and assumptions. Probabilities of recurrence and death were based on data from the COMBI-AD trial and an indirect treatment comparison. Medication costs were based on wholesale acquisition cost prices. Costs of distant recurrence were from a health insurance claims study. RESULTS: In a hypothetical population of 1 million commercially insured members, 48 patients were estimated to become eligible for treatment with dabrafenib and trametinib in combination over the 3-year projection period; in the new scenario, 10 patients were projected to receive such treatment. Cumulative costs of melanoma-related care were estimated to be $6.3 million in the reference scenario and $6.9 million in the new scenario. The budget impact of dabrafenib and trametinib in combination was an increase of $549 thousand overall and 1.5 cents per member per month. CONCLUSIONS: For a hypothetical U.S. commercial health plan of 1 million members, the budget impact of dabrafenib and trametinib in combination as adjuvant treatment for melanoma is likely to be relatively modest and within the range of published estimates for oncology therapies. These results may assist payers in making coverage decisions regarding the use of adjuvant dabrafenib and trametinib in melanoma. DISCLOSURES: Funding for this research was provided to Policy Analysis Inc. (PAI) by Novartis Pharmaceuticals. Stellato, Moynahan, and Delea are employed by PAI. Ndife, Koruth, Mishra, and Gunda are employed by Novartis. Ghate was employed by Novartis at the time of this study and is shareholder in Novartis, Provectus Biopharmaceuticals, and Mannkind Corporation. Gerbasi was employed by PAI at the time of this study and is currently an employee, and stockholder, of Sage Therapeutics. Delea reports grant funding from Merck and research funding from Amgen, Novartis, Sanofi, Seattle Genetics, Takeda, Jazz, EMD Serono, and 21st Century Oncology, unrelated to this work.

Cost-effectiveness of dabrafenib and trametinib in combination as adjuvant treatment of BRAF V600E/K mutation-positive melanoma from a US healthcare payer perspective.

Objective: The COMBI-AD trial demonstrated the efficacy and safety of dabrafenib and trametinib in combination vs placebo as adjuvant treatment of patients with BRAF V600E/K mutation-positive resected Stage IIIA (lymph node metastasis >1 mm), IIIB, or IIIC melanoma. This analysis evaluated the cost-effectiveness of dabrafenib and trametinib vs observation from a US healthcare payer perspective.Methods: This evaluation employed a non-homogeneous, semi-Markov, cohort model with health states for relapse-free survival (RFS), post-locoregional recurrence (LR), post-distant recurrence (DR) receiving first-line treatment, and post-DR receiving second-line treatment. A 50-year modeling time horizon was used. Transition probabilities were estimated based on individual patient data (IPD) from the COMBI-AD trial. Health-state utilities were estimated using EuroQol (EQ-5D) index values from COMBI-AD and published sources. Direct medical costs associated with treatment of melanoma were considered, including costs of BRAF mutation testing, medication and administration costs for adjuvant and metastatic treatments, costs of treating recurrence, and costs of adverse events. Costs and quality-adjusted life-years (QALYs) were discounted at 3.0% annually.Results: Compared with observation, adjuvant dabrafenib and trametinib was estimated to result in a gain of 2.15 QALYs at an incremental cost of $74,518. The incremental cost-effectiveness ratio (ICER) was estimated to be $34,689 per QALY. In deterministic sensitivity analyses, the ICER was sensitive to the cost of dabrafenib and trametinib and the distribution used for projecting RFS beyond the end of follow-up in the COMBI-AD trial. At a cost-effectiveness threshold of $100,000 per QALY, the probability that dabrafenib and trametinib is cost-effective was estimated to be 92%.Conclusions: Given generally-accepted cost-effectiveness threshold values in the US, dabrafenib plus trametinib is likely to be a cost-effective adjuvant therapy for patients with BRAF mutation positive melanoma. These results may be useful for policy-makers in their deliberations regarding reimbursement and access to this treatment.