Cost-Effectiveness and Net Monetary Benefit of Olaparib Maintenance Therapy Versus No Maintenance Therapy After First-line Platinum-based Chemotherapy in Newly Diagnosed Advanced BRCA1/2-mutated Ovarian Cancer in the Italian National Health Service.

PURPOSE: The aim of this study was to evaluate the cost-effectiveness and net monetary benefit of olaparib maintenance therapy compared with no maintenance therapy after first-line platinum-based chemotherapy in newly diagnosed advanced BRCA1/2-mutated ovarian cancer from the Italian National Health Service (NHS) perspective. METHODS: We developed a lifetime Markov model in which a cohort of patients with newly diagnosed advanced BRCA1/2-mutated ovarian cancer was assigned to receive either olaparib maintenance therapy or active surveillance (Italian standard of care) after first-line platinum-based chemotherapy to compare cost-effectiveness and net monetary benefit of the 2 strategies. Data on clinical outcomes were obtained from related clinical trial literature and extrapolated using parametric survival analyses. Data on costs were derived from Italian official sources and relevant real-world studies. The incremental cost-effectiveness ratio (ICER), incremental cost-utility ratio (ICUR), and incremental net monetary benefit (INMB) were computed and compared against an incremental cost per quality-adjusted life-year (QALY) gained of €16,372 willingness-to-pay (WTP) threshold. We used deterministic sensitivity analysis (DSA) and probabilistic sensitivity analysis (PSA) to assess how uncertainty affects results; we also performed scenario analyses to compare results under different pricing settings. FINDINGS: In the base-case scenario, during a 50-year time horizon, the total costs for patients treated with olaparib therapy and active surveillance were €124,359 and €97,043, respectively, and QALYs gained were 7.29 and 4.88, respectively, with an ICER of €9,515 per life-year gained, an ICUR of €11,345 per QALY gained, and an INMB of €12,104. In scenario analyses, considering maximum selling prices for all other drugs, ICUR decreased to €11,311 per QALY and €7,498 per QALY when a 10% and 20% discount, respectively, was applied to the olaparib official price, and the INMB increased to €12,186 and €21,366, respectively. DSA found that the model results were most sensitive to the proportion of patients with relapsing disease in response to platinum-based chemotherapy, time receiving olaparib first-line maintenance treatment, and subsequent treatments price. According to PSAresults, olaparib was associated with a probability of being cost-effective at a €16,372 per QALY WTP threshold ranging from 70% to 100% in the scenarios examined. IMPLICATIONS: Our analysis indicates that olaparib maintenance therapy may deliver a significant health benefit with a contained upfront cost during a 50-year time horizon, from the Italian NHS perspective, providing value in a setting with curative intent.

Budget impact of niraparib as maintenance treatment in recurrent ovarian cancer following platinum-based chemotherapy.

Aim: To estimate financial implications of adopting niraparib as maintenance treatment in recurrent ovarian cancer. Materials & methods: A model was developed to estimate the budget impact of treating patients with niraparib compared with alternative maintenance treatment options (olaparib, rucaparib, bevacizumab or 'watch and wait') over 3 years. Results: For a hypothetical plan with 1 million lives representative of US/Medicare-only populations, projected cost savings with niraparib were US$78,721/$293,723, $276,671/$1,009,729 and $353,585/$1,289,712 at years 1, 2 and 3, respectively. Sensitivity analyses showed prices of niraparib, rucaparib and olaparib to have the most significant impact on the budget. Conclusion: Factoring in all treatment-related costs, the use of niraparib could result in significant cost savings compared with other maintenance treatment options.

Cost-effectiveness analysis of first-line pembrolizumab treatment for PD-L1 positive, non-small cell lung cancer in China.

PURPOSE: Pembrolizumab was recently approved in several countries as a first-line treatment for patients with PD-L1 positive, non-small cell lung cancer (NSCLC). However, it is expensive. This study aimed to assess the cost-effectiveness of pembrolizumab in treating advanced NSCLC patients with PD-L1 positive cancer in China. METHODS: A Markov model was developed to compare the cost-effectiveness of pembrolizumab with chemotherapy for patients with PD-L1 expression on at least 50% of NSCLC tumor cells. Model inputs for transition probabilities and toxicity were derived from published clinical trial data, while health utilities were estimated from a literature review. Costs for drugs were updated to standard fee data from West China Hospital in 2017. Health outcomes were measured in quality-adjusted life years (QALYs), and cost-effectiveness was measured as the incremental cost-effectiveness ratio (ICER). Sensitivity analyses were conducted to test the robustness of the model. RESULTS: Pembrolizumab gained 0.45 QALYs at an incremental cost of $46,362 compared to chemotherapy for an ICER of $103,128 per QALY gained. In most scenarios, the ICER exceeded three times the Chinese Gross Domestic Product per capita. Two-way sensitivity analysis showed that, when the utility of the progression-free status increased to the maximal value of 0.845 and the 1 mg dose price decreased to $10.50, the ICER reduced to $25,216/QALY. CONCLUSIONS: Pembrolizumab is not likely to be cost-effective in the treatment of PD-L1 positive, NSCLC for Chinese patients. Less aggressive pricing may increase accessibility for patients in China.

Cost-effectiveness of pembrolizumab in combination with chemotherapy in the 1st line treatment of non-squamous NSCLC in the US.

AIMS: To describe cost-effectiveness of pembrolizumab plus platinum and pemetrexed chemotherapy in metastatic, non-squamous, NSCLC patients in the US. MATERIALS AND METHODS: A model is developed utilizing partitioned survival analysis to estimate the cost-effectiveness of KEYNOTE-189 trial comparators pembrolizumab + chemotherapy (carboplatin/cisplatin + pemetrexed) vs chemotherapy alone. Clinical efficacy, treatment utilization, health utility, and safety data are derived from the trial and projected over 20 years. For extrapolating survival beyond the trial, a novel SEER population-data approach is applied (primary analysis), with separate estimation via traditional parametric extrapolation methods. Costs for drugs and non-drug disease management are also incorporated. Based on an indirect treatment comparison, cost-effectiveness of pembrolizumab + chemotherapy vs pembrolizumab monotherapy is evaluated for patients with programmed death-ligand 1 (PD-L1) ≥ 50%. RESULTS: In the full non-squamous population, pembrolizumab + chemotherapy is projected to increase life expectancy by 2.04 years vs chemotherapy (3.96 vs 1.92), for an approximate doubling of life years. Resultant incremental cost-effectiveness ratios (ICERs) are $104,823/QALY and $87,242/life year. In patients with PD-L1 ≥ 50% and 1-49%, life expectancy is more than doubled (4.53 vs 1.88 years) and (4.87 vs 2.01 years), with a 32% (2.60 vs 1.97 years) increase in PD-L1 < 1% patients. Corresponding incremental costs/quality-adjusted life year (QALY) are $103,402, $66,837, and $183,529 for PD-L1 ≥ 50%, 1-49%, and <1% groups, respectively. Versus pembrolizumab monotherapy in PD-L1 ≥ 50% patients, representing current standard of care, pembrolizumab + chemotherapy increases life expectancy by 65% (4.53 vs 2.74 years) at an ICER of $147,365/QALY. LIMITATIONS AND CONCLUSIONS: The addition of pembrolizumab to chemotherapy is projected to extend life expectancy to a point not previously seen in previously untreated metastatic non-squamous NSCLC. Although ICERs vary by sub-group and comparator, results suggest pembrolizumab + chemotherapy yields ICERs near, or in most cases, well below a 3-times US per capita GDP threshold of $180,000/QALY, and may be a cost-effective first-line treatment for metastatic non-squamous NSCLC patients.

Cost-effectiveness Analysis of Nivolumab for Treatment of Platinum-Resistant Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck.

Background: The CheckMate 141 trial found that nivolumab improved survival for patients with recurrent or metastatic head and neck cancer (HNC). Despite the improved survival, nivolumab is much more expensive than standard therapies. This study assesses the cost-effectiveness of nivolumab for the treatment of HNC. Methods: We constructed a Markov model to simulate treatment with nivolumab or standard single-agent therapy for patients with recurrent or metastatic platinum-refractory HNC. Transition probabilities, including disease progression, survival, and probability of toxicity, were derived from clinical trial data, while costs (in 2017 US dollars) and health utilities were estimated from the literature. Incremental cost-effectiveness ratios (ICERs), expressed as dollar per quality-adjusted life-year (QALY), were calculated, with values of less than $100 000/QALY considered cost-effective from a health care payer perspective. We conducted one-way and probabilistic sensitivity analyses to assess model uncertainty. Results: Our base case model found that treatment with nivolumab increased overall cost by $117 800 and improved effectiveness by 0.400 QALYs compared with standard therapy, leading to an ICER of $294 400/QALY. The model was most sensitive to the cost of nivolumab, though nivolumab only became cost-effective if the cost per cycle decreased from $13 432 to $3931. The model was not particularly sensitive to assumptions about survival. If one assumed that all patients alive at the end of the CheckMate 141 trial were cured of their disease, nivolumab was still not cost-effective (ICER $244 600/QALY). Conclusion: While nivolumab improves overall survival, at its current cost it would not be considered a cost-effective treatment option for patients with HNC.

Cost-utility analysis of platinum-based chemotherapy versus taxane and other regimens for ovarian cancer.

OBJECTIVES: Most economic evaluations of chemotherapies for ovarian cancer patients have used hypothetical cohorts or randomized control trials, but evidence integrating real-world survival, cost, and utility data is limited. METHODS: A propensity score-matched cohort of 6856 elderly (≥65 years) ovarian cancer patients diagnosed from 1991 to 2005 from the Surveillance, Epidemiology, and End Results-Medicare data cohort were included. Treatment regimens (i.e., no chemotherapy, platinum-based only, platinum plus taxane, and other nonplatinum) were identified in the 6 months postdiagnosis. Patients were followed until death or end of study (December 2006). Effectiveness was measured in quality-adjusted life-years (QALYs), and total health care costs were measured by using a payer's perspective (2009 US dollars). Methodological and statistical uncertainties were accounted by including alternative scenarios (for utility values) and net monetary benefit approach. Incremental cost-effectiveness ratios (ICERs) were calculated, and stratified analyses were performed by tumor stages and age groups. RESULTS: On comparing the platinum-based group versus no chemotherapy, we found that the ICER was $30,073/QALY and $58,151/QALY for early- and late-stage disease, respectively, while other nonplatinum and platinum plus taxane groups were dominated (less effective and more costly). Similar results were found across alternative scenarios and age groups. For patients 85 years or older, platinum plus taxane, however, was not dominated by the platinum-based group, with an ICER of $133,892/QALY. CONCLUSIONS: Following elderly ovarian cancer patients over a lifetime using real-world longitudinal data and adjusting for quality of life, we found that treatment with platinum-based regimen was the most cost-effective treatment alternative.

Markov-modeling for the administration of platinum analogues and paclitaxel as first-line chemotherapy as well as topotecan and liposomal doxorubicin as second-line chemotherapy with epithelial ovarian carcinoma.

PURPOSE: So far there is no analysis available on the cost effectiveness of the paclitaxel/platinum-analogue combination versus carboplatin monotherapy with ovarian cancer. Up-to-now only a cost-utility analysis on ovarian carcinoma has been published (Ortega et al. in Gynecol Oncol 66(3):454-463, 1997), which in addition to the first-line chemotherapy included second-line chemotherapy with effectiveness and cost data in the analysis. Therefore, within the scope of our study the cost effectiveness of platinum analogues and paclitaxel as first-line chemotherapy as well as topotecan and liposomal doxorubicin as second-lie chemotherapy was to be determined with epithelial ovarian carcinoma. METHODS: For this purpose a decision-making Markov model was developed which represents the medical and economic consequences of the administration of paclitaxel and platinum derivatives in first-line chemotherapy and the administration of topotecan and liposomal doxorubicin in second-line chemotherapy in the treatment of epithelial ovarian carcinoma by means of data from the literature. Patients were treated either in the early (FIGO stage I-IIa) or advanced stage (FIGO stage IIb-IV). RESULTS: The therapeutic strategy caboplatin followed by topotecan costs 20,123.91 euros, the therapeutic strategy carboplatin followed by liposomal doxorubicin 22,336.57 euros, the therapeutic strategy carboplatin/pactlitaxel followed by liposomal topotecan 29,820.64 euros and the therapeutic strategy carboplatin/paclitaxel followed by liposomal doxorubicin 31,560.47 euros from the time of diagnosis until death or survival within 5 years. With lives saved, accordingly of 2.55, 2.70, 2.60 and 2.65 years' costs amounted to 7,891 euros, 8,270.35 euros, and 11,453.62 euros per year of life saved. CONCLUSIONS: Based on the threshold value of social willingness to pay 45,500 euros per year of life saved, the therapeutic strategy carboplatin followed by topotecan, the therapeutic strategy carboplatin followed by liposomal doxorubicin, the therapeutic strategy carboplatin/paclitaxel followed by topotcan and the therapeutic strategy carboplatin/paclitaxel followed by liposomal doxorubicin can be evaluated to be cost effective.