Cost-Effectiveness of Nab-Paclitaxel and Gemcitabine Versus Gemcitabine Monotherapy for Patients with Unresectable Metastatic Pancreatic Cancer in Japan.

OBJECTIVES: The purpose of this study was to evaluate the cost-effectiveness of nab-paclitaxel and gemcitabine (GnP) compared with gemcitabine monotherapy (G) for patients with unresectable metastatic pancreatic cancer in Japan from the perspective of healthcare payer. METHODS: A partitioned survival analysis model was developed to predict costs and quality-adjusted life years (QALYs) for GnP and G. The time horizon of the model was set at 20 years. An annual discount rate of 2% for both costs and QALYs was applied. Data on overall survival and progression-free survival were derived from the Metastatic Pancreatic Adenocarcinoma Clinical Trial. Cost parameters were estimated from a Japanese medical claims database. The incremental cost-effectiveness ratio (ICER) of GnP compared with G was estimated. One-way sensitivity analysis was performed to assess the uncertainty in the parameter settings. In addition, scenario and probability sensitivity analyses were performed. RESULTS: The incremental cost and QALY of GnP compared with G were US$25 089 and 0.13 QALY, respectively. The ICER of GnP was estimated to be US$192 992 per QALY gained. Although the ICER was influenced by utility parameters and the survival curves, the ICERs remained higher than the willingness to pay (WTP) threshold of US$68 000 (JPY 7.5 million). The probability that GnP becomes cost-effective compared with G was estimated to be 29.2%. CONCLUSIONS: Applying the WTP threshold of US$68 000 per QALY, GnP was not cost-effective for patients with unresectable metastatic pancreatic cancer in Japan from the perspective of healthcare payer. Further research is needed to obtain utility data from Japanese patients with pancreatic cancer.

Cost-effectiveness analysis of FOLFIRINOX vs gemcitabine with nab-paclitaxel as adjuvant treatment for resected pancreatic cancer in the United States based on PRODIGE-24 and APACT trials.

BACKGROUND: Pancreatic cancer is associated with low median overall survival. Combination chemotherapy regimens FOLFIRINOX and gemcitabine with nab-paclitaxel (GemNab) are the new adjuvant treatment standards for resectable pancreatic cancer. PRODIGE-24 and APACT trials demonstrated superior clinical outcomes with FOLFIRINOX and GemNab, each vs gemcitabine monotherapy. OBJECTIVE: To evaluate the cost-effectiveness of FOLFIRINOX vs GemNab for resectable pancreatic cancer in adults from the U.S. payer perspective, in order to inform decision makers about which of these treatments is optimal. METHODS: A Markov model with 3 disease states (relapse free, progressive disease, and death) was developed. Cycle length was 1 month, and time horizon was 10 years. Transition probabilities were derived from PRODIGE-24 and APACT survival data. All cost and utility input parameters were obtained from published literature. Cost-effectiveness analysis was performed to obtain total costs, quality-adjusted life-years (QALYs), life-years (LYs), and incremental cost-effectiveness ratio (ICER). A 3% annual discount rate was applied to costs and outcomes. The effect of uncertainty on model parameters was assessed with 1-way and probabilistic sensitivity analysis (PSA). RESULTS: Our analysis estimated that the cost for FOLFIRINOX was $40,831 higher than GemNab ($99,669 vs. $58,837). Despite increased toxicity, FOLFIRINOX was associated with additional 0.18 QALYs and 0.25 LYs compared with GemNab (QALY: 1.65 vs. 1.47; LY: 2.09 vs. 1.84). The ICER for FOLFIRINOX vs GemNab was $226,841 per QALY and $163,325 per LY. FOLFIRINOX was not cost-effective at a willingness-to-pay (WTP) threshold of $200,000 per QALY, and this was confirmed by the PSA. CONCLUSIONS: Total monthly cost for FOLFIRINOX was approximately 1.7 times higher than GemNab. If the WTP threshold increases to or above $250,000 per QALY, FOLFIRINOX then becomes a cost-effective treatment option. DISCLOSURES: This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors. The authors have no conflicts of interest to declare.

Pembrolizumab and lenvatinib versus carboplatin and paclitaxel as first-line therapy for advanced or recurrent endometrial cancer: A Markov analysis.

OBJECTIVE: To determine the cost effectiveness of pembrolizumab/lenvatinib (P/L) versus standard-of-care carboplatin/paclitaxel (C/T) as first-line systemic therapy for patients with advanced/recurrent endometrial cancer. METHODS: We designed a Markov model to simulate treatment outcomes for advanced/recurrent endometrial cancer patients whose tumors are either microsatellite stable (MSS) or have high microsatellite instability (MSI-high). We adopted a healthcare sector perspective for the analysis. Model inputs for costs, health utility, and clinical estimates were obtained from the literature including data from GOG0209 and KEYNOTE-146. Primary outcomes included costs of care, quality-adjusted life years (QALYs), and the incremental cost-effectiveness ratio (ICER). The time-horizon was three years and the discount rate was 3% annually. RESULTS: In a MSS cohort, compared to C/T, first-line treatment with P/L increased treatment costs by $212,670 and decreased QALYs by 0.28 per patient. In a MSI-high cohort, compared to C/T, P/L increased costs by $313,487 and increased QALYs by 0.11 per patient, representing an ICER of $2,849,882 per QALY. Sensitivity analyses found that the price of the new drugs was the most important determinant of the ICER and that the price of the new drugs would need to decrease by 85% to $2817 per cycle to reach a $150,000/QALY threshold. CONCLUSION: In the MSS model, we found that first-line therapy for advanced or recurrent endometrial cancer with P/L increased costs and worsened outcomes compared to C/T. In the MSI-high model, P/L improved survival and QALYs compared to C/T but was not cost-effective at the current cost of the drugs.

Trastuzumab with carboplatin/paclitaxel for treatment of advanced stage and recurrent uterine papillary serous carcinoma: A cost-effectiveness analysis.

OBJECTIVE: Uterine papillary serous carcinoma (UPSC) is a variant of endometrial cancer that is aggressive and associated with poor outcomes. We sought to evaluate the cost effectiveness of carboplatin/paclitaxel alone versus carboplatin/paclitaxel with trastuzumab among patients with Her2/neu-positive advanced or recurrent UPSC. METHODS: We designed a Markov model in TreeAge Pro 2019 software to simulate management of a theoretical cohort of 4000 patients with Her2/neu-positive advanced or recurrent uterine papillary serous carcinoma (UPSC) followed for four years. In the carboplatin/paclitaxel with trastuzumab strategy, we included the cost of testing for Her2/neu status. We obtained all model inputs from the literature and a societal perspective was assumed. Outcomes included progression-free survival, progression, UPSC-specific mortality, cost, and quality-adjusted life years (QALYs). The intervention was considered cost effective if the incremental cost-effectiveness ratio (ICER) was below the willingness-to-pay threshold of $100,000 per QALY. Sensitivity analyses were used to determine the robustness of the results. RESULTS: In our theoretical cohort of 4000 women, treatment with the addition of trastuzumab resulted in 637 fewer deaths and 627 fewer cases of progression compared with treatment with carboplatin/paclitaxel alone. Treatment with trastuzumab was associated with an additional cost of $144,335,895, but was associated with an increase of 2065 QALYs. The ICER was $69,903 per QALY, which was below our willingness-to-pay threshold. Sensitivity analysis demonstrated that this treatment strategy was cost-effective until the cost of 6 months of treatment surpassed $38,505 (baseline input: $27,562). CONCLUSION: We found that the addition of trastuzumab to carboplatin/paclitaxel was a cost-effective treatment strategy for patients with advanced/recurrent Her2/neu-positive UPSC.

Cost-Effectiveness of Neoadjuvant-Adjuvant Treatment Strategies for Women With ERBB2 (HER2)-Positive Breast Cancer.

Importance: The neoadjuvant treatment options for ERBB2-positive (also known as HER2-positive) breast cancer are associated with different rates of pathologic complete response (pCR). The KATHERINE trial showed that adjuvant trastuzumab emtansine (T-DM1) can reduce recurrence in patients with residual disease compared with patients treated with trastuzumab; however, T-DM1 and other ERBB2-targeted agents are costly, and understanding the costs and health consequences of various combinations of neoadjuvant followed by adjuvant treatments in the United States is needed. Objective: To examine the costs and disease outcomes associated with selection of various neoadjuvant followed by adjuvant treatment strategies for patients with ERBB2-positive breast cancer. Design, Setting, and Participants: In this economic evaluation, a decision-analytic model was developed to evaluate various neoadjuvant followed by adjuvant treatment strategies for women with ERBB2-positive breast cancer from a health care payer perspective in the United States. The model was informed by the KATHERINE trial, other clinical trials with different regimens from the KATHERINE trial, the Flatiron Health Database, McKesson Corporation data, and other evidence in the published literature. Starting trial median age for KATHERINE patients was 49 years (range, 24-79 years in T-DM1 arm and 23-80 years in trastuzumab arm). The model simulated patients receiving 5 different neoadjuvant followed by adjuvant treatment strategies. Data analyses were performed from March 2019 to August 2020. Exposure: There were 4 neoadjuvant regimens: (1) HP: trastuzumab (H) plus pertuzumab (P), (2) THP: paclitaxel (T) plus H plus P, (3) DDAC-THP: dose-dense anthracycline/cyclophosphamide (DDAC) plus THP, (4) TCHP: docetaxel (T) plus carboplatin (C) plus HP. All patients with pCR, regardless of neoadjuvant regimen, received adjuvant H. Patients with residual disease received different adjuvant therapies depending on the neoadjuvant regimen according to the 5 following strategies: (1) neoadjuvant DDAC-THP followed by adjuvant H, (2) neoadjuvant DDAC-THP followed by adjuvant T-DM1, (3) neoadjuvant THP followed by adjuvant DDAC plus T-DM1, (4) neoadjuvant HP followed by adjuvant DDAC/THP plus T-DM1, or (5) neoadjuvant TCHP followed by adjuvant T-DM1. Main Outcomes and Measures: Lifetime costs in 2020 US dollars and quality-adjusted life-years (QALYs) were estimated for each treatment strategy, and incremental cost-effectiveness ratios were estimated. A strategy was classified as dominated if it was associated with fewer QALYs at higher costs than the alternative. Results: In the base-case analysis, costs ranged from $415 833 (strategy 3) to $518 859 (strategy 4), and QALYs ranged from 9.67 (strategy 1) to 10.73 (strategy 3). Strategy 3 was associated with the highest health benefits (10.73 QALYs) and lowest costs ($415 833) and dominated all other strategies. Probabilistic analysis confirmed that this strategy had the highest probability of cost-effectiveness (>70% at willingness-to-pay thresholds of $0-200,000/QALY) and was associated with the highest net benefit. Conclusions and Relevance: These results suggest that neoadjuvant THP followed by adjuvant H for patients with pCR or followed by adjuvant DDAC plus T-DM1 for patients with residual disease was associated with the highest health benefits and lowest costs for women with ERBB2-positive breast cancer compared with other treatment strategies considered.

Cost-Effectiveness of the Addition of Bevacizumab to First-Line Chemotherapy With Carboplatin and Paclitaxel in Patients With Non-Small Cell Lung Cancer.

OBJECTIVES: To evaluate the incremental cost-effectiveness ratio (ICER) of the addition of bevacizumab to first-line chemotherapy with carboplatin and paclitaxel in patients with non-small cell lung cancer (NSCLC) from the perspective of the Colombian health system. METHODS: A Markov model was employed to evaluate the cost-effectiveness of bevacizumab + carboplatin + paclitaxel (BCP) compared with carboplatin + paclitaxel (CP) in the treatment of NSCLS during a 4-year period. The health outcome was the number of life-years gained (LYG) and quality-adjusted life-years (QALYs) obtained from the survival curves reported in a clinical study. Costs were estimated using national tariff and reported in US dollars at a date in 2019. Costs and effectiveness outcomes were discounted at a rate of 3.5% per year. A probabilistic sensitivity analysis was performed on important parameters with a Monte Carlo simulation. RESULTS: The costs of BCP and CP were $30 341 and $11 735, respectively. The LYG for BCP and CP were 0.34 and 0.29, respectively. The QALY for BCP and CP were 0.27 and 0.23. The ICER of BCP versus CP was $ 465 150 QALY. The results of the Monte Carlo simulation showed that CP was cost-effective in 100% of the iterations compared with BCP. CONCLUSION: The addition of bevacizumab to the scheme carboplatin + paclitaxel compared to carboplatin + paclitaxel for NSCLC is not cost-effective from the point of view of the Colombian health system.

Economic Evaluation of Cisplatin Plus Gemcitabine Versus Paclitaxel Plus Gemcitabine for the Treatment of First-Line Advanced Metastatic Triple-Negative Breast Cancer in China: Using Markov Model and Partitioned Survival Model.

INTRODUCTION: This study aimed to evaluate the cost-effectiveness of cisplatin plus gemcitabine vs. paclitaxel plus gemcitabine as a first-line treatment for metastatic triple-negative breast cancer in China. METHODS: The Markov model and partitioned survival (PS) model were used, and the study included three health states over the period of a lifetime. Transition probabilities and safety data were derived from the CBCSG006 trial (cisplatin plus gemcitabine vs. paclitaxel plus gemcitabine in patients who had acquired metastatic triple-negative breast cancer). Cost and utility values were derived from previous studies, the Chinese Drug Bidding Database, and healthcare documents. Sensitivity analyses were performed to observe model stability. RESULTS: In the Markov model, compared with paclitaxel plus gemcitabine, cisplatin plus gemcitabine yielded an additional 0.15 QALYs, with an incremental cost of 1976.33 USD. The incremental cost-utility ratio (ICUR) was 12,826.98 USD/QALY (quality-adjusted life year). In the PS model, cisplatin plus gemcitabine yielded an additional 0.17 QALYs with an incremental cost of 2384.63 USD; the incremental cost-utility ratio (ICUR) was 13,867.7 USD/QALY. In the first scenario analysis, in which the 3-year time horizon was used in both arms, the total QALYs in the cisplatin plus gemcitabine group were larger and the costs were lower, indicating that cisplatin plus gemcitabine was superior to paclitaxel plus gemcitabine. In the second scenario, in which the progression-free (PF) utility (during chemotherapy) was 0.76, the PF utility was 0.96, and the post-progression (PP) utility was 0.55, the result obtained with the Markov model showed that the ICUR was 11,063.68 USD/QALY. In the probabilistic sensitivity analysis (PSA) on the Markov model, the probabilities that cisplatin plus gemcitabine would be cost-effective were 48.94-78.72% if the willingness-to-pay threshold was 9776.8 to 29,330.4 USD/QALY. CONCLUSIONS: The findings of the present analysis suggest that cisplatin plus gemcitabine might be much more cost-effective than paclitaxel plus gemcitabine in patients receiving first-line treatment for metastatic triple-negative breast cancer in China.

Cost-effectiveness analysis of atezolizumab in advanced triple-negative breast cancer.

BACKGROUND: The IMpassion130 trial demonstrated that adding atezolizumab to nanoparticle albumin-bound (nab)-paclitaxel improved the survival of patients with untreated, advanced, programmed death ligand 1 (PDL1)-positive triple-negative breast cancer (TNBC). In view of the high cost of immunotherapy, it is important to examine its value with respect to both benefits and costs. In this study, the cost-effectiveness of atezolizumab/nab-paclitaxel combination therapy relative to nab-paclitaxel monotherapy was evaluated for the first-line treatment of advanced, PDL1-positive TNBC, from a healthcare system perspective. METHODS: A three-state partitioned-survival model was developed to compare the clinical and economic outcomes of treatment with atezolizumab/nab-paclitaxel combination therapy with nab-paclitaxel monotherapy in patients with advanced TNBC. Clinical data were obtained from the IMpassion130 trial and extrapolated to 5 years. Health state utilities were retrieved from the literature, while direct costs (in Singapore dollars, S$) were sourced from public healthcare institutions in Singapore. The primary outcomes of the model were life years (LYs), quality-adjusted LYs (QALYs), costs and incremental cost-effectiveness ratios (ICERs). One-way and probabilistic sensitivity analyses and scenario analyses were conducted to explore the impact of specific assumptions and uncertainties. RESULTS: Adding atezolizumab to nab-paclitaxel resulted in an additional 0.361 QALYs (0.636 LYs) at an ICER of S$324,550 per QALY gained. The ICER remained high at S$67,092 per QALY even when atezolizumab was priced zero. One-way sensitivity analysis showed that the ICER was most sensitive to variations in the cost of atezolizumab and the time horizon. Scenario analyses confirmed that the ICERs remained high even under extremely favourable assumptions. CONCLUSIONS: Given the exceedingly high ICER, adding atezolizumab to nab-paclitaxel was unlikely to represent good value for money for the treatment of advanced PDL1-positive TNBC. Our findings will be useful in informing funding policy decisions alongside other considerations such as comparative effectiveness, unmet need and budget impact.

Cost-Effectiveness of ramucirumab plus paclitaxel as a second-line therapy for advanced gastric or gastro-oesophageal cancer in China.

AIM: That clinical trial (RAINBOW) showed that a 7.4 months overall survival benefit with the combination therapy with ramucirumab (RAM) and paclitaxel (PAC) as second-line therapy for patients with recurrent or metastatic gastric or gastro-oesophageal junction adenocarcinoma, compared with placebo (PLA) plus paclitaxel. We performed an analysis to assess the cost-effectiveness of RAM from a Chinese perspective and recognized the range of drug costs. METHODS: By building a Markov model to estimate quality-adjusted life-years (QALYs), life-years (LYs) and lifetime costs. Transition probabilities, costs and utilities were estimated for the published literature, Chinese health care system and local price setting. We performed threshold analyses and probabilistic sensitivity analyses to evaluate the uncertainty of the model. RESULTS: Compared with PLA strategy, RAM strategy provided an incremental survival benefit of 1.22 LYs and 0.64 QALYs. The probabilistic sensitivity analysis showed that when RAM costs less than $151 or $753 per 4 weeks, the incremental cost-effectiveness ratio (ICER) approximated the willingness-to-pay threshold (WTP), suggesting that there was 50% likelihood that the ICER for RAM + PAC would be less than $44528.4 per QALY or $48121 per QALY, respectively. CONCLUSIONS: For patients with advanced gastric or gastro-oesophageal junction adenocarcinoma who fail first-line chemotherapy, our results are conducive to the multilateral drug price guidance negotiations of RAM in China.

First-Line Treatment With Atezolizumab Plus Nab-Paclitaxel for Advanced Triple-Negative Breast Cancer: A Cost-Effectiveness Analysis.

OBJECTIVE: The authors conducted a cost-effectiveness analysis incorporating recent phase III clinical trial (IMpassion130) data to evaluate the cost-effectiveness of atezolizumab in combination with nab-paclitaxel (AnP) against nab-paclitaxel alone as the first-line treatment for advanced triple-negative breast cancer in developed and developing countries. MATERIALS AND METHODS: A decision-analytic Markov model was developed using IMpassion130 data to evaluate the cost-effectiveness of AnP over a lifetime from the US health care payer and Chinese health care system perspective. Model inputs were derived from IMpassion130 and published literature. The primary outcomes of the model were quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratios (ICERs). Uncertainty was addressed using univariate and probabilistic sensitivity analyses. RESULTS: For the intention-to-treat (ITT) population, the projected mean outcome was better with AnP (1.41 QALYs) than with nab-paclitaxel alone (0.99 QALYs). Similar results were obtained for the programmed death ligand 1 (PD-L1)-positive population, with the obtained mean outcomes of 1.66 and 0.88 QALYs, respectively. For the Unites States, the ICER values comparing AnP with nab-paclitaxel were US$331,996.89 and US$229,359.88 per QALY gained for the ITT and PD-L1-positive populations, respectively. For China, the ICER values were US$106,339.26 and US$72,971.88 per QALY gained for the ITT and PD-L1-positive populations, respectively. The univariate sensitivity analysis indicated that the price of atezolizumab was the most influential factor in our study. AnP had 0% cost-effectiveness at the willingness-to-pay thresholds of US$150,000/QALY in the United States and US$29,383/QALY in China. CONCLUSION: AnP is not a cost-effective choice as the first-line treatment for advanced triple-negative breast cancer in the United States and China.

High-effective biosynthesis of baccatin â ¢ by using the alternative acetyl substrate, N-acetyl-d-glucosamine.

AIMS: Paclitaxel is a type of broad-spectrum anticancer drug in short supply. The price of acetyl-CoA (17 709 677·4 USD mol-1 ), which is the acetyl group donor for the enzymatic synthesis of the intermediate, baccatin Ⅲ, is still the bottleneck of the mass production of paclitaxel. This study reports a novel acetyl group donor, which could substantially reduce the cost of production. METHODS AND RESULTS: In this study, a substrate spectrum with 14 kinds of representative acetyl-donor substitutes predicted by computer-aided methods was tested in a 10-deacetylbaccatin Ⅲ-10-O-acetyltransferase (DBAT) heterogeneous-expressed open-whole-cell catalytic system. The results of computer prediction and experimental analysis revealed the rule of the acetyl-donor compounds based on this substrate spectrum. N-acetyl-d-glucosamine (30·95 USD mol-1 , about 572 202-fold cheaper than acetyl-CoA) is selected as a suitable substitute under the rule. The yield when using N-acetyl-d-glucosamine as acetyl donor in open-whole-cell catalytic system was 2·13-fold of that when using acetyl-CoA. In the in vivo system, the yield increased 24·17%, which may indicate its cooperation with acetyl-CoA. CONCLUSION: The success of open-whole-cell synthesis and in vivo synthesis of baccatin Ⅲ by adding N-acetyl-d-glucosamine as acetyl substrate demonstrates that it is a useful substrate to improve the yield of baccatin Ⅲ. SIGNIFICANCE AND IMPACT OF THE STUDY: All these findings provided a potential acetyl-donor substitute for acetyl-CoA, as well as a low cost and efficient method of preparing paclitaxel through baccatin Ⅲ semi-synthesis.

The Market Reacts Quickly: Changes in Paclitaxel Vascular Device Purchasing Within the Ascension Healthcare System.

BACKGROUND: A meta-analysis of trials in endovascular therapy suggested an increased mortality associated with treatment exposure to paclitaxel. Multiple publications and corrections of prior data were performed, and the United States Food and Drug Administration has issued multiple advisories regarding paclitaxel use. We analyzed how this controversy impacted device purchasing and related utilization patterns in the period immediately following publication of the meta-analysis. METHODS AND RESULTS: Ascension Healthcare System purchase data over a 14-month period were synthesized across centers for both paclitaxel and non-paclitaxel devices. A fixed-effects regression model and a binary regression model with facility-level controls were used to compare purchasing patterns before and after the meta-analysis. Purchase volumes of each paclitaxel device fell. Pooled purchase volumes of all paclitaxel devices decreased from a 14-month peak of 631 devices in October 2018 to a 14-month nadir of 359 devices in February 2019. An F-test comparing the pooled-month specific fixed effects for the months before vs after the publication of the meta-analysis has an F-statistic of 11.64, suggesting that average purchasing levels in the two periods are statistically different (P<.001). Utilization of non-paclitaxel devices did not decline. CONCLUSIONS: Purchase volumes of paclitaxel devices decreased immediately during the months following publication of the related meta-analysis. Total Ascension-wide paclitaxel device purchase volume in February 2019 demonstrated a 43.1% reduction from peak monthly purchase volume during the assessed period and a 32.5% reduction compared with November 2019, the last month preceding publication of the meta-analysis.

Cost-effectiveness of Osimertinib as a Second-line Treatment in Patients With EGFR-mutated Advanced Non-Small Cell Lung Cancer in China.

PURPOSE: To assess the cost-effectiveness of osimertinib used as a second-line treatment after failure of epidermal growth factor receptor tyrosine kinase inhibitor therapy for advanced non-small cell lung cancer (NSCLC) in China. METHODS: From the perspective of China's health care system, a Markov model was used for estimating the costs and health outcomes of osimertinib and 4 platinum-based chemotherapies, including pemetrexed + platinum (PP), gemcitabine + platinum (GP), docetaxel + platinum (DP), and paclitaxel + platinum (TP). Two scenarios were considered, one in all confirmed patients with T790M-positive disease (scenario 1) and the other in all patients whose disease progressed after epidermal growth factor receptor tyrosine kinase inhibitor therapy, which consisted of patients with T790M-positive or T790M-negative NSCLC (scenario 2). Clinical data for transition probabilities and treatment effects were obtained from published clinical trials. Health care resource utilization and costs were derived from local administrative databases and published literature. Deterministic and probabilistic sensitivity analyses were conducted to assess the uncertainty of the results. FINDINGS: In the base-case analysis, compared with the 4 platinum-based chemotherapies, osimertinib yielded an additional 0.671 to 0.846 quality-adjusted life-year (QALY), with incremental costs of 15,943 to 20,299 USD in scenario 1, and an additional 0.376 to 0.808 QALY with incremental costs of 9710 to 15,407 USD in scenario 2. In the probabilistic sensitivity analysis, the probabilities that osimertinib would be cost-effective were 57.7% in scenario 1 and 58.4% in scenario 2 if the willingness-to-pay threshold were 30,000 USD/QALY, and probabilities would be more than 75 % in both scenarios if the willingness-to-pay threshold were 50,000 USD/QALY. IMPLICATIONS: Osimertinib is likely to be cost-effective when used as a second-line treatment of advanced NSCLC in China based on the latest reimbursement price of osimertinib through National Reimbursement Drug List negotiation.

Cost-effectiveness of Atezolizumab Combination Therapy for First-Line Treatment of Metastatic Nonsquamous Non-Small Cell Lung Cancer in the United States.

Importance: Immune checkpoint inhibitor combination therapy has recently become the standard of care for first-line treatment of metastatic nonsquamous non-small cell lung cancer. The implications of these first-line treatments are considerable, given the potential population of patients eligible to receive them and their high cost. Objective: To evaluate the cost-effectiveness of adding atezolizumab to bevacizumab, carboplatin, and paclitaxel as a first-line treatment strategy for patients with metastatic nonsquamous non-small cell lung cancer in the United States. Design, Setting, and Participants: In this economic evaluation, a primary microsimulation model was developed to assess atezolizumab combination vs bevacizumab, carboplatin, and paclitaxel alone in the first line (base case 1). A secondary model was developed to assess these treatments along with pembrolizumab combination and platinum doublet chemotherapy (base case 2). Treatment strategies and other simulated conditions were based on those from the IMpower150 and KEYNOTE-189 clinical trials. The study perspective was the US health care sector. One million patients with metastatic nonsquamous non-small cell lung cancer were simulated for each treatment group. This study was performed from February 2019 through May 2019. Main Outcomes and Measures: Incremental cost-effectiveness ratios were compared with a willingness-to-pay threshold of $100 000 per quality-adjusted life-year (QALY). Results: In base case 1, in which 1 million patients were simulated, treating with bevacizumab, carboplatin, and paclitaxel in the first line was associated with a mean cost of $112 551 (95% CI, $112 450-$112 653) and a mean survival of 1.48 QALYs (95% CI, 1.47-1.48 QALYs) per patient. Atezolizumab plus bevacizumab, carboplatin, and paclitaxel was associated with a mean cost of $244 166 (95% CI, $243 864-$244 468) and a mean survival of 2.13 QALYs (95% CI, 2.12-2.13 QALYs) per patient, for an estimated incremental cost-effectiveness ratio of $201 676 per QALY (95% CI, $198 105-$205 355 per QALY). In base case 2, in which 1 million patients were simulated, pembrolizumab combination therapy was associated with a mean cost of $226 282 (95% CI, $226 007-$226 557) and a mean survival of 2.45 QALYs (95% CI, 2.44-2.46 QALYs) per patient. Pembrolizumab combination dominated atezolizumab plus bevacizumab, carboplatin, and paclitaxel, leading to an incremental cost-effectiveness ratio of $116 698 per QALY (95% CI, $115 088-$118 342 per QALY) between pembrolizumab combination and bevacizumab, carboplatin, and paclitaxel. Atezolizumab combination was not cost-effective at a willingness-to-pay threshold of $100 000 per QALY. Conclusions and Relevance: In this simulated model economic analysis, atezolizumab combination was not cost-effective compared with bevacizumab, carboplatin, and paclitaxel and provided suboptimal incremental benefit compared with cost vs pembrolizumab combination for first-line treatment. Although atezolizumab combination therapy provides clinical benefits, price reductions may be necessary for this treatment strategy to become cost-effective.

Cost-effectiveness of adjuvant paclitaxel and trastuzumab for early-stage node-negative, HER2-positive breast cancer.

OBJECTIVES: Adjuvant paclitaxel and trastuzumab has been shown to be an effective regimen with low risk of cancer recurrence and treatment-related toxicities in early-stage node-negative, HER2-positive breast cancer. We investigated the cost-effectiveness of this regimen. METHODS: A Markov-based microsimulation model with six health states is used to simulate four adjuvant therapy options for women with early-stage node-negative, HER2-positive breast cancer at different age groups. The four treatment arms are 1) adjuvant paclitaxel and trastuzumab (TH), 2) doxorubicin, cyclophosphamide, paclitaxel and trastuzumab (ACTH), 3) docetaxel, carboplatin and trastuzumab (TCH), and 4) no adjuvant trastuzumab (NT). Data from randomized trials were used to estimate treatment efficacy. Societal perspective was used in this cost-effectiveness analysis. Costs were measured in 2016 US dollars (US$) and quality-adjusted life-years (QALYs) was used for health outcomes. Sensitivity analyses were performed to evaluate the impact of uncertainty in parameter estimation. RESULTS: We found that 40-year-old women undergoing TH treatment would have an average of 16.17 QALYs for the cost of $178,650 when lifetime horizon is used. Compared to NT, TH has incremental cost-effectiveness ratios ranged from $10,584 (ages 40-49) to $84,981 (age 80+) per additional QALYs. The sensitivity analysis showed that TH is cheaper and leads to higher QALYs compared to both ACTH and TCH for all age groups and time horizons. CONCLUSIONS: TH is cost-effective for all age groups in the base case scenario and in the sensitivity analysis. In order to reduce the parameter uncertainty, clinical trials with longer follow-up times are needed.

Bio-production of Baccatin III, an Important Precursor of Paclitaxel by a Cost-Effective Approach.

Natural production of anti-cancer drug taxol from Taxus has proved to be environmentally unsustainable and economically unfeasible. Currently, bioengineering the biosynthetic pathway of taxol is an attractive alternative production approach. 10-deacetylbaccatin III-10-O-acetyl transferase (DBAT) was previously characterized as an acyltransferase, using 10-deacetylbaccatin III (10-DAB) and acetyl CoA as natural substrates, to form baccatin III in the taxol biosynthesis. Here, we report that other than the natural acetyl CoA (Ac-CoA) substrate, DBAT can also utilize vinyl acetate (VA), which is commercially available at very low cost, acylate quickly and irreversibly, as acetyl donor in the acyl transfer reaction to produce baccatin III. Furthermore, mutants were prepared via a semi-rational design in this work. A double mutant, I43S/D390R was constructed to combine the positive effects of the different single mutations on catalytic activity, and its catalytic efficiency towards 10-DAB and VA was successfully improved by 3.30-fold, compared to that of wild-type DBAT, while 2.99-fold higher than the catalytic efficiency of WT DBAT towards 10-DAB and Ac-CoA. These findings can provide a promising economically and environmentally friendly method for exploring novel acyl donors to engineer natural product pathways.

Paclitaxel as Albumin-Bound Nanoparticles with Gemcitabine for Untreated Metastatic Pancreatic Cancer: An Evidence Review Group Perspective of a NICE Single Technology Appraisal.

As part of the single technology appraisal (STA) process, the National Institute for Health and Care Excellence (NICE) invited Celgene Ltd to submit clinical and cost-effectiveness evidence for paclitaxel as albumin-bound nanoparticles (Nab-Pac) in combination with gemcitabine (Nab-Pac + Gem) for patients with untreated metastatic pancreatic cancer. The STA was a review of NICE's 2015 guidance (TA360) in which Nab-Pac + Gem was not recommended for patients with untreated metastatic pancreatic cancer. The review was prompted by a proposed Patient Access Scheme (PAS) discount on the price of Nab-Pac and new evidence that might lead to a change in the guidance. The Liverpool Reviews and Implementation Group at the University of Liverpool was the Evidence Review Group (ERG). This article summarises the ERG's review of the company's evidence submission for Nab-Pac + Gem, and the Appraisal Committee (AC) decision. The final scope issued by NICE listed three comparators: gemcitabine monotherapy (Gem), gemcitabine in combination with capecitabine (Gem + Cap), and a combination of oxaliplatin, irinotecan, leucovorin and fluorouracil (FOLFIRINOX). Clinical evidence for the comparison of Nab-Pac + Gem versus Gem was from the phase III CA046 randomized controlled trial. Analysis of progression-free survival (PFS) and overall survival (OS) showed statistically significant improvement for patients treated with Nab-Pac + Gem versus Gem. Clinical evidence for the comparison of Nab-Pac + Gem versus FOLFIRINOX and versus Gem + Cap was derived from a network meta-analysis (NMA). Results of the NMA did not indicate a statistically significant difference in OS or PFS for the comparison of Nab-Pac + Gem versus either Gem + Cap or FOLFIRINOX. The ERG's main concerns with the clinical effectiveness evidence were difficulties in identifying the patient population for whom treatment with Nab-Pac + Gem is most appropriate, and violation of the proportional hazards (PH) assumption in the CA046 trial. The ERG highlighted methodological issues in the cost-effectiveness analysis pertaining to the modelling of survival outcomes, estimation of drug costs and double counting of adverse-event disutilities. The AC accepted all the ERG's amendments to the company's cost-effectiveness model; however, these did not make important differences to the incremental cost-effectiveness ratios (ICERs). The company's base-case ICER was £46,932 per quality-adjusted life-year (QALY) gained for the comparison of Nab-Pac + Gem versus Gem. Treatment with Nab-Pac + Gem was dominated both by treatment with Gem + Cap and with FOLFIRINOX in the company's base case. The AC concluded that the most plausible ICER for treatment with Nab-Pac + Gem versus Gem was in the range of £41,000-£46,000 per QALY gained. The AC concluded that Nab-Pac + Gem was not cost effective compared with Gem + Cap or FOLFIRINOX, and accepted that treatment with Nab-Pac + Gem met the end-of-life criteria versus Gem but did not consider Nab-Pac + Gem to meet the end-of-life criteria compared with Gem + Cap or FOLFIRINOX. The AC also concluded that although patients who would receive Nab-Pac + Gem rather than FOLFIRINOX or Gem + Cap were difficult to distinguish, they were identifiable in clinical practice. The AC recommended treatment with Nab-Pac + Gem for patients with untreated metastatic pancreatic cancer for whom other combination chemotherapies were unsuitable and who would otherwise receive Gem.

Cost-effectiveness of Paclitaxel + Ramucirumab Combination Therapy for Advanced Gastric Cancer Progressing After First-line Chemotherapy in Japan.

PURPOSE: The combination of paclitaxel + ramucirumab is a standard second-line treatment in patients with advanced gastric cancer. This therapy has been associated with increased median overall survival and progression-free survival compared with those with paclitaxel monotherapy. We evaluated the cost-effectiveness of paclitaxel + ramucirumab combination therapy in patients with advanced gastric cancer, from the perspective of health care payers in Japan. METHODS: We constructed a Markov model to compare, over a time horizon of 3 years, the costs and effectiveness of the combination of paclitaxel + ramucirumab and paclitaxel alone as second-line therapies for advanced gastric cancer in Japan. Health outcomes were measured in life-years (LYs) and quality-adjusted (QA) LYs gained. Costs were calculated using year-2016 Japanese yen (¥1 = US $17.79) according to the social insurance reimbursement schedule and drug tariff of the fee-for-service system in Japan. Model robustness was addressed through 1-way and probabilistic sensitivity analyses. The costs and QALYs were discounted at a rate of 2% per year. The willingness-to-pay threshold was set at the World Health Organization's criterion of ¥12 million, because no consensus exists regarding the threshold for acceptable cost per QALY ratios in Japan's health policy. FINDINGS: Paclitaxel + ramucirumab combination therapy was estimated to provide an additional 0.09 QALYs (0.10 LYs) at a cost of ¥3,870,077, resulting in an incremental cost-effectiveness ratio of ¥43,010,248/QALY. The incremental cost-effectiveness ratio for the combination therapy was >¥12 million/QALY in all of the 1-way and probabilistic sensitivity analyses. IMPLICATIONS: Adding ramucirumab to a regimen of paclitaxel in the second-line treatment of advanced gastric cancer is expected to provide a minimal incremental benefit at a high incremental cost per QALY. Based on our findings, adjustments in the price of ramucirumab, as well as improves in other clinical parameters such as survival time and adverse event in advanced gastric cancer therapy, are needed.

The Pharmacological Costs of Second-Line Treatments for Recurrent Ovarian Cancer.

INTRODUCTION: In ovarian cancer, it is uncertain which chemotherapy regimen is more clinically effective and cost-effective for the treatment of recurrence; therefore, it might be interesting to make a balance between the cost of the drugs administered and the difference in progression-free survival (PFS) and overall survival (OS). METHODS: The present evaluation was restricted to pivotal phase 3 randomized controlled trials. We calculated the pharmacological costs necessary to get the benefit in PFS and OS. The costs of drugs are at the pharmacy of our hospital and are expressed in Euros (&OV0556;). We have subsequently applied the European Society for Medical Oncology Magnitude of Clinical Benefit Scale. RESULTS: Our study evaluated 3 phase 3 randomized controlled trials, including 2004 patients. The most relevant increase of costs was associated with the combination chemotherapy including trabectedin, with the highest costs for month of PFS gained (15,836 &OV0556;) and for month of OS gained (7198 &OV0556;), but it substantially differs considering the data of partially platinum-sensitive populations (platinum-free interval of 6-12 months), with 3959 &OV0556; for month of OS gained. CONCLUSIONS: The addition of trabectedin to pegylated liposomal doxorubicin for the treatment of recurrent ovarian cancer can lead to an increase of pharmacological costs. Differently, considering OS in patients with platinum-free interval of 6 to 12 months, there is a halving of pharmacological costs with the addition of trabectedin to pegylated liposomal doxorubicin. These costs are in line with the spending suggested as sustainable (thresholds of <$61,500 per life-year gained).

ASCO Value Framework Highlights the Relative Value of Treatment Options in Ovarian Cancer.

PURPOSE: The ASCO value framework allows physicians and patients to compare the relative value of novel treatments. Our aim was to assess the value of three frontline ovarian cancer therapies by using this framework. METHODS: From phase III, randomized controlled clinical trial (RCT) data, the net health benefits (NHBs) for three frontline ovarian cancer treatment options-dose-dense paclitaxel (Japanese Gynecologic Oncology Group study JGOG 3016), intraperitoneal (IP)/intravenous (IV) chemotherapy (Gynecologic Oncology Group [GOG] study GOG 172), and concurrent plus maintenance bevacizumab (GOG 218 and the Seventh International Collaborative Ovarian Neoplasm study [ICON7])-were calculated. The ASCO value framework calculates the NHB by using six criteria: clinical benefit, toxicity, tail of the curve, symptom palliation, treatment-free interval, and quality of life. Clinical benefit calculation uses ASCO-assigned importance weights for overall survival and progression-free survival. The maximum possible NHB points is 180. NHBs were presented alongside the drug-acquisition cost (DAC) of each therapy. A benefit-cost ratio of NHB points per additional cost was calculated. RESULTS: The NHB of dose-dense paclitaxel was 38, at an additional cost of $16 per cycle. IP cisplatin/IV + IP paclitaxel received 29 NHB points, at an additional cost of $1,629 per cycle. Concurrent plus maintenance bevacizumab received 24 NHB points, at an additional cost of $7,581 per cycle (GOG 218) or six NHB points ($3,790 per cycle; ICON7). The ratios of NHB points-to-dollar were as follows: dose-dense paclitaxel, 2.4 (highest); IP chemotherapy, 0.018; and bevacizumab, 0.003 (lowest). CONCLUSION: Using the ASCO value framework, we constructed value snapshots of three major frontline therapeutic options in ovarian cancer. Dose-dense paclitaxel provided the highest additional value when analysis accounted for NHB and cost. However, additional research is needed to include individual patient preferences and provide personalized value assessments.