Budget impact analysis of the novel PD-1 inhibitor toripalimab versus pembrolizumab in recurrent or metastatic nasopharyngeal carcinoma.

AIM: To estimate the budget impact of adding a toripalimab regimen as a treatment option to the existing pembrolizumab regimen, both including gemcitabine and cisplatin, in untreated recurrent/metastatic nasopharyngeal carcinoma (R/M NPC) using the published wholesale acquisition cost (WAC) and average sales price (ASP). METHODS: Budget impact analysis comparing a treatment mix "without" versus "with" the toripalimab regimen in the US eligible annual incident R/M NPC population, a 3-year time horizon, toripalimab/pembrolizumab market splits of 60/40 (Y1) and 80/20 (Y2/3), and medication adjustments for discontinuation or progression. Cost inputs included drugs, administration, and adverse event (AE) management. The models were replicated for a hypothetical 1-million-member health plan in which costs per-member-per-month (PMPM) and per-member-per-year (PMPY) were estimated. One-way (OWSA) and probabilistic sensitivity analyses (PSA) as well as scenario analyses were performed. RESULTS: In the "without" scenario, the 3-year WAC-based costs for the pembrolizumab regimen total $1,449,695,333 ($1,305,632,448 for treatment and $144,062,885 for managing AEs). In the "with" scenario, total 3-year costs for pembrolizumab decline to $380,012,135 with toripalimab adding $885,505,900 ($779,206,567 for treatment and $106,299,333 for AE management). Annual net savings range from $46,526,152 in 2024 to $71,194,214 in 2026, for 3-year savings of $184,177,298. Associated net savings in a 1-million-member health plan are $543,068 over 3 years with savings of $0.045 PMPM and $0.543 PMPY. The ASP-based model shows similar patterns with 3-year net savings of $174,235,983 in the US incident population and savings of $0.043 PMPM and $0.514 PMPY in a 1-million-member health plan. The PSA support base case findings; OWSA and scenario analyses reveal how parameter variability impacts results. CONCLUSION: Savings between $174 million and $184 million can be achieved from treating 60% of R/M NPC patients in year 1 and 80% in years 2 and 3 with the toripalimab regimen over a similar pembrolizumab regimen.

Toripalimab, a human monoclonal anti-body that targets PD-1, was recently approved by the US Food and Drug Administration (FDA) for the first-line treatment of adults with metastatic or recurrent, locally advanced nasopharyngeal carcinoma (NPC), in combination with gemcitabine and cisplatin. We evaluated how much it would cost a payor to cover the FDA-approved toripalimab plus gemcitabine and cisplatin regimen (the toripalimab regimen) to a non-FDA-approved pembrolizumab plus gemcitabine and cisplatin regimen (the pembrolizumab regimen). With no trial data available for such pembrolizumab regimen, we assumed that it would be comparable to the toripalimab regimen in efficacy and safety. Our model adopted a 3-year time horizon and assumed a 60/40 market share split in year 1 and an 80/20 market split in years 2 and 3. It included two US cost inputs: the wholesale acquisition cost (WAC) or "list price" at market entry and, as no average sales price (ASP) will be available for toripalimab for several quarters, a toripalimab price point of 80% of the pembrolizumab ASP. We adjusted for patients whose cancer progressed or who discontinued treatment to determine the number of fully-treated-patient-equivalents. We found that treating 60% of NPC patients in year 1 and 80% in years 2 and 3 with the toripalimab regimen instead of the pembrolizumab regimen generates, for the entire adjusted patient population, savings ranging from $174 million when using ASP to $184 million when using WAC.

Toripalimab plus chemotherapy in American patients with recurrent or metastatic nasopharyngeal carcinoma: A cost-effectiveness analysis.

BACKGROUND: Toripalimab, combined with gemcitabine and cisplatin, has been approved as the first-line treatment for recurrent or metastatic nasopharyngeal carcinoma (RM-NPC), representing a significant milestone as the first FDA-approved innovative therapy for this condition. Despite this achievement, there's a lack of data on the cost-effectiveness of toripalimab for RM-NPC patients in the American context. METHODS: To assess the cost-effectiveness of toripalimab plus chemotherapy versus chemotherapy alone, a 3-state partitioned survival model was constructed. The study involved participants with characteristics matching those in the JUPITER-02 trial. Cost and utility inputs were collected from literature. Main outcomes measured were quality-adjusted life year (QALY), and incremental cost-effectiveness ratio (ICER). Univariate and probabilistic sensitivity analyses, subgroup analyses, and scenario analyses were conducted to verify the robustness of results. RESULTS: The study found that the toripalimab regimen resulted in 4.390 QALYs at a cost of $361,813, while the chemotherapy-only regimen yielded 1.685 QALYs at a cost of $161,632. This translates to an ICER of $74,004/QALY, below the willingness-to-pay threshold of $150,000/QALY. Sensitivity analyses indicated that utility values, discount rate, and the price of toripalimab significantly impact INMB. With an 87.10% probability of being cost-effective at a $150,000/QALY threshold, the probabilistic sensitivity analysis supports toripalimab plus chemotherapy as a viable option. Scenario analysis showed that toripalimab remains cost-effective unless its price increases by 125%. Additionally, a simulated 15-year study period increases the ICER to $88,026/QALY. Subgroup analysis revealed ICERs of $76,538/QALY for PD-L1 positive and $70,158/QALY for PD-L1 negative groups. CONCLUSIONS: Toripalimab in combination with chemotherapy is likely to be a cost-effective alternative to standard chemotherapy for American patients with RM-NPC. This evidence can guide clinical and reimbursement decision-making in treating RM-NPC patients.

Cost-effectiveness analysis of different treatment modalities in BCG-unresponsive NMIBC.

OBJECTIVE: Radical cystectomy (RC) is the standard of care (SOC) in BCG-unresponsive NMIBC and is associated with a significant health-related quality-of-life burden. Recently, promising results have been published on Gemcitabine/Docetaxel, Pembrolizumab, and Hyperthermic Intravesical Chemotherapy (HIVEC) as salvage therapy options trying to increase the rate of bladder preservation. Here, we performed a Cost-Effectiveness-Analysis of those treatment modalities. PATIENTS AND METHODS: We developed a Markov model from a payer's perspective drawing on clinical data of single-arm trials testing intravesical gemcitabine/docetaxel and pembrolizumab in BCG-unresponsive NMIBC, as well as clinical data from patients receiving hyperthermic intravesical chemotherapy HIVEC (n = 29) as intravesical salvage chemotherapy at our uro-oncological centre in Cologne. Costs were simulated utilising a non-commercial diagnosis-related groups grouper, utilities were derived from comparable cost-effectiveness studies. We used a Monte Carlo simulation to identify the optimal treatment, comparing the incremental cost effectiveness ratios (ICERs) at a willingness-to-pay threshold of €50 000 (euro)/quality-adjusted life year (QALY). RESULTS: Over a horizon of 10 years, gemcitabine/docetaxel, HIVEC, and pembrolizumab were associated with costs of €48 353, €64 438, and €204 580, as well as a gain of QALYs of 6.16, 6.48, and 6.00, resulting in an ICER of €26 482, €42 567, and €184 533 respectively, in comparison to RC with total costs of €21 871 and a gain of QALYs of 5.01. Monte Carlo simulation identified HIVEC as the treatment of choice under assumption of a WTP of <€50 000. CONCLUSION: Considering a WTP of <€50 000/QALY, gemcitabine/docetaxel and HIVEC are highly cost-effective therapeutic options in BCG-refractory NMIBC, while RC remains the cheapest option. At its current price, pembrolizumab would only be cost-effective assuming a price reduction of at least 70%.

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.

The Association of Drug-Funding Reimbursement With Survival Outcomes and Use of New Systemic Therapies Among Patients With Advanced Pancreatic Cancer.

Importance: Gemcitabine-nab-paclitaxel (GEMNAB) and fluorouracil, leucovorin, irinotecan, and oxaliplatin (FOLFIRINOX) both improve survival of patients with advanced pancreatic cancer when compared with single-agent gemcitabine in clinical trials. Objective: To describe changes in the survival of patients with advanced pancreatic cancer associated with sequential drug-funding approvals and to determine if there exist distinct patient populations for whom GEMNAB and FOLFIRINOX are associated with survival benefit. Design, Setting, and Participants: This population-based, retrospective cohort study examined all incident cases of advanced pancreatic cancer treated with first-line chemotherapy in Ontario, Canada (2008-2018) that were identified from the Cancer Care Ontario (Ontario Health) New Drug Funding Program database. Statistical analysis was performed from October 2020 to January 2021. Exposures: First-line chemotherapy for advanced pancreatic cancer. Main Outcomes and Measures: The main outcomes were the proportion of patients treated with each chemotherapy regimen over time and overall survival for each regimen. Cox proportional hazards regression models were used to compare overall survival between treatment regimens after adjustment for confounding variables, inverse probability of treatment weighting, and matching. Results: From 2008 to 2018, 5465 patients with advanced pancreatic cancer were treated with first-line chemotherapy in Ontario, Canada. The median (range) age of patients was 66.9 (27.8-93.4) years; 2447 (45%) were female; 878 (16%) had prior pancreatic resection, and 328 (6%) had prior adjuvant gemcitabine. During the time period when only gemcitabine and FOLFIRINOX were funded (2011-2015), 49% (929 of 1887) received FOLFIRINOX. When GEMNAB was subsequently funded (2015-2018), 9% (206 of 2347) received gemcitabine, 44% (1034 of 2347) received FOLFIRINOX, and 47% (1107 of 2347) received GEMNAB. The median overall survival increased from 5.6 months (95% CI, 5.1-6.0 months) in 2008 to 2011 to 6.9 months (95% CI, 6.5-7.4 months) in 2011 to 2015 to 7.6 months (95% CI, 7.1-8.0 months) in 2015 to 2018. Patients receiving FOLFIRINOX were younger and healthier than patients receiving GEMNAB. After adjustment and weighting, FOLFIRINOX was associated with better overall survival than GEMNAB (hazard ratio [HR], 0.75 [95% CI, 0.69-0.81]). In analyses comparing patients treated with GEMNAB and gemcitabine, GEMNAB was associated with better overall survival (HR, 0.86 [95% CI, 0.78-0.94]). Conclusions and Relevance: This cohort study of patients with advanced pancreatic cancer receiving first-line palliative chemotherapy within a universal health care system found that drug funding decisions were associated with increased uptake of new treatment options over time and improved survival. Both FOLFIRINOX and GEMNAB were associated with survival benefits in distinct patient populations.

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.

Social and Clinical Correlates of Neoadjuvant Chemotherapy in Medicare Beneficiaries With Muscle Invasive Bladder Cancer From 2004-2015.

OBJECTIVE: To assess social and clinical correlates of neoadjuvant chemotherapy (NAC) utilization among Medicare beneficiaries. MATERIALS AND METHODS: A cohort of SEER-Medicare (2004-2015) patients with muscle-invasive bladder cancer treated by radical cystectomy were stratified into 3-groups: standard of care NAC (cisplatin-based combination), non-standard of care NAC, and upfront cystectomy. Multivariable logistic regression analysis was used to assess social, demographic and clinical correlates of each treatment category. Survival analyses were performed to compare propensity matched treatment groups. RESULTS: In total, 6214 patients were identified with a median follow-up of 21 [IQR 7-54] months. NAC utilization increased from 10.7% to 39.1%, between 2004 and 2015, largely due to increased use of standard of care regimens. The most commonly used nonstandard regimen was gemcitabine/carboplatin (50.2%). Older age, Hispanic and Black race, lower socioeconomic status, and contraindications to cisplatin were associated with increased odds of receiving nonstandard of care NAC compared to standard of care. Standard of care NAC was associated with improved overall survival HR 0.85 (95% CI 0.76, 0.94) and HR 0.75 (95% CI 0.63, 0.89) compared to both upfront cystectomy and nonstandard of care NAC, respectively. CONCLUSION: NAC utilization has increased to nearly 40%; however, the use of non-standard of care NAC regimen have persisted (~8%). Cisplatin-ineligibility, older age, race/ethnicity, and lower socioeconomic status were correlated with nonstandard of care NAC, which provided no clinical benefit at the risk of potential harm. In accordance with current clinical guidelines, cisplatin-ineligible patients should be considered for timely upfront cystectomy or novel clinical trials.

The economic burden of metastatic pancreatic cancer.

BACKGROUND: Objectives: Pancreatic cancer (PC) is a costly disease with a limited life-expectancy as it generally presents as an advanced, metastatic disease. Though current literature suggests cost varies by first line treatment, there is limited real-world knowledge about the economic burden of pancreatic cancer. This study describes the economic burden of pancreatic cancer patients overall and by observed first line treatments. METHODS: The IBM MarketScan databases were used to identify adult metastatic PC patients from January 1, 2010 through 3/31/2017. Those without other primary cancers, pregnancy, or prior PC treatment, and with 6 months of continuous enrollment prior to PC were included. Treatment patterns and healthcare utilization and expenditures were measured during the variable-length follow-up period. Continuous measures were presented as per patient per month (PPPM). RESULTS: A total of 6,360 patients met all inclusion criteria. Almost half (46.8%) of patients were untreated. Gemcitabine alone (15.6%) and FOLFIRINOX (11.4%) were the most commonly observed first line regimens. Treated patients incurred $17,513 PPPM (Gemcitabine alone) to $27,889 PPPM (FOLFIRINOX) during follow-up. Untreated patients incurred the highest unadjusted ($30,777 PPPM) and adjusted ($20,392 PPPM) cost. CONCLUSIONS: Metastatic PC patients incur a high economic burden driven by high utilization of healthcare resources, which varies by first line treatment. Also, the high proportion of untreated patients is alarming as these patients may be the most expensive of all patients. There is an unmet need in these patients for effective treatments that also reduce their economic burden.

Cost-effectiveness of Capecitabine + Irinotecan Versus Leucovorin + Fluorouracil + Irinotecan in the Second-line Treatment of Metastatic Colorectal Cancer in China.

PURPOSE: The AXEPT trial demonstrated that modified XELIRI (mXELIRI; capecitabine + irinotecan) was noninferior to standard treatment with FOLFIRI (fluorouracil + leucovorin + irinotecan), both ± bevacizumab, in the treatment of metastatic colorectal cancer (mCRC). The present study was designed to evaluate the cost-effectiveness of mXELIRI versus FOLFIRI as a second-line treatment of mCRC. METHODS: We developed a Markov model to estimate the costs and health outcomes of mXELIRI and FOLFIRI in patients with mCRC from the Chinese payer perspective. Survival data, transition probabilities, and health utility values were obtained from published studies. The costs of drugs were obtained from the West China Hospital. Life-years (LYs), quality-adjusted life-years (QALYs) gained, incremental cost-utility ratio (ICUR), and incremental cost-effectiveness ratio (ICER) values were regarded as the primary end points. One-way sensitivity analysis and probabilistic sensitivity analysis were performed to evaluate the impact of uncertainty of parameters in the analysis. FINDINGS: The effectiveness was found to be 0.48 QALYs (1.14 LYs) in the mXELIRI arm and 0.41 QALYs (1.05 LYs) in the FOLFIRI arm, with total costs of 29,896.41 US dollars (USD) in the mXELIRI arm and 28,894.68 USD in the FOLFIRI arm. The ICER and ICUR with mXELIRI versus FOLFIRI were 11,130.33 USD/LY and 14,310.43 USD/QALY gained, which were less than the willingness-to-pay threshold in China (25,840.88 USD/QALY). IMPLICATIONS: Based on the results of this study, mXELIRI was found to be a cost-effective alternative to FOLFIRI as a second-line treatment of mCRC in patients in China.

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.

Real-World Assessment of Health Care Costs for Patients with Metastatic Pancreatic Cancer Following Initiation of First-Line Chemotherapy.

BACKGROUND: Management of metastatic pancreatic ductal adenocarcinoma (mPDA) places a significant financial burden on the U.S. health care system because of such factors as treatment with multidrug chemotherapy regimens, management of chemotherapy-related adverse events, and disease- or treatment-related hospitalizations. Depending on functional status, first-line chemotherapy regimens that are guideline recommended include nab-paclitaxel with gemcitabine (AG) and FOLFIRINOX (FFX), the combination of fluorouracil, leucovorin, irinotecan, and oxaliplatin. However, few previous studies have examined overall health care costs associated with mPDA management. OBJECTIVE: To describe health care costs following initiation of first-line treatment with AG or FFX among patients with mPDA. METHODS: Retrospective cohorts of first-line AG and FFX initiators were constructed from the MarketScan database (2014-2017). The index date was the date of first-line AG or FFX initiation. Included patients had insurance enrollment for 6 months before the index date. Total cumulative health care costs and costs from outpatient services, inpatient admissions, emergency department visits, chemotherapy administrations, and pharmacy dispensing were assessed within 12 months after the index date (i.e., 0-1, 0-2, …, 0-12 months). Patient-level cost data began accruing from the first paid claim and continued accruing until the censoring date. RESULTS: A total of 2,199 patients with mPDA initiated first-line AG (n = 1,352) or FFX (n = 847). Compared with AG initiators, FFX patients were younger (mean age 59 vs. 63 years) and had better baseline health status, with fewer having diabetes (43% vs. 57%) or coronary artery disease (12% vs. 22%). Median follow-up was 5.4 and 7.2 months for AG and FFX, respectively. Median first-line treatment duration was 2.1 months with AG and 2.3 months with FFX. Six months following first-line treatment initiation, total cumulative health care costs (median) were $85,714 (95% CI = $79,683-$91,788) and $114,116 (95% CI = $105,816-$119,591) for AG and FFX initiators, respectively. Outpatient services contributed the largest fractional cost for both groups. CONCLUSIONS: Total health care costs for patients with mPDA who initiated FFX or AG are driven mostly by outpatient rather than inpatient costs. Further research, using comparative methodology, is warranted to fully understand cost drivers and whether higher costs for FFX patients relate primarily to use of FFX or higher underlying use of outpatient care among FFX patients. DISCLOSURES: This study was funded by Halozyme Therapeutics. Oestreicher and Yeganegi were employees of Halozyme Therapeutics at the time of the study and were involved in study design, data interpretation, and the decision to submit the data for publication. Bullock reports advisory board fees from Eisai, Exelixis, Bayer, and Taiho and consulting fees from Halozyme Therapeutics, outside the submitted work. Rowan reports consulting fees from Halozyme Therapeutics, during the conduct of the study. Chiorean reports grants and consulting fees from Celgene and Halozyme Therapeutics; grants from Lilly, Stemline, Ignyta, Roche, Merck, Boehringer-Ingelheim, Bristol Meyer Squibb, Incyte, Macrogenics, Rafael, and AADi; and consulting fees from Astra Zeneca, Array, Eisai, Ipsen, Five Prime Therapeutics, Seattle Genetics, Vicus, and Legend, outside the submitted work.

Cost-effectiveness analysis of gemcitabine plus cisplatin versus docetaxel, cisplatin and fluorouracil for induction chemotherapy of locoregionally advanced nasopharyngeal carcinoma.

BACKGROUND: Recently, patients who received induction chemotherapy plus concurrent chemoradiotherapy for locoregionally advanced nasopharyngeal carcinoma were found to have survival advantages compared with those receiving concurrent chemoradiotherapy alone in two large randomized trials. Based on these two trials, we present a cost-effectiveness analysis to compare gemcitabine and cisplatin (GP) versus cisplatin, fluorouracil, and docetaxel (TPF) for induction chemotherapy to treat locoregionally advanced nasopharyngeal carcinoma. METHODS: We constructed a Markov model to compare the cost and effectiveness of GP versus TPF. Clinical data including the frequency of adverse events, recurrence and death obtained from two randomized phase III trials were used to calculate transition probabilities and costs. Health utilities were estimated from the literature. Incremental cost-effectiveness ratios, expressed as dollars per quality-adjusted life-year (QALY), were calculated, and incremental cost-effectiveness ratios less than $27,534.25/QALY (3 × the per capita GDP of China, 2018) were considered cost-effective. One-way sensitivity and probabilistic sensitivity analyses explored the robustness of the model. RESULTS: Our base case model found that the total cost was $53,082.68 in the GP group and $45,482.66 in the TPF group. The QALYs were 6.82 and 4.11, respectively. The incremental cost-effectiveness ratio favoured the GP regimen, at an incremental cost of $2,804.44 per QALY. The probabilistic sensitivity analysis found that treatment with the GP regimen was cost-effective 100% of the time at a willingness-to-pay threshold of $27,534.25‬/QALY. CONCLUSION: In this model, GP was estimated to be cost-effective compared with cisplatin, fluorouracil, and docetaxel for patients with locoregionally advanced nasopharyngeal carcinoma from the payer's perspectives in the China.

S-1 or gemcitabine adjuvant therapy in resected pancreatic cancer: a cost-effectiveness analysis based on the JASPAC-01 trial.

Purpose: This study aimed to investigate the cost-effectiveness of adjuvant treatments in resected pancreatic cancer.Methods: A Markov model was developed to mimic the disease process of postoperative pancreatic cancer, encompassing three health states (relapse-free survival, recurrent disease, and death). Health outcomes and utility scores were derived from the phase III trial and available literature. Cost data were calculated using standard fee data from the West China Hospital for 2017. One-way sensitivity analyses and probabilistic sensitivity analyses were developed to explore model uncertainty.Results: Treatment with S-1 was estimated to yield 1.61 quality-adjusted life-years (QALYs) at a cost of $25,696, whereas treatment with gemcitabine yielded 1.27 QALYs at a cost of $28,930. The incremental cost-effectiveness ratio of S-1 versus gemcitabine was $-9,490 per QALY. Based on the willingness-to-pay threshold of $25,841 per QALY, the net monetary benefit (NMB) was $15,786 for S-1 and $3,727 for gemcitabine, generating the incremental NMB of $12,059. A probabilistic sensitivity analysis revealed that the probabilities of S-1 and gemcitabine being cost-effective were 92% and 8%, respectively. Results were robust to changes in parameters.Conclusion: Adjuvant therapy using S-1 is a cost-effective alternative compared to gemcitabine in patients with postoperative pancreatic cancer from the Chinese societal perspective.

Cost-effectiveness analysis of gemcitabine plus cisplatin versus fluorouracil plus cisplatin in the first-line setting for Chinese patients with metastatic nasopharyngeal carcinoma.

PURPOSE: A randomized phase III trial demonstrated that gemcitabine plus cisplatin (GP) prolonged progression-free survival and overall survival compared with fluorouracil plus cisplatin (FP) as first-line chemotherapy in patients with metastatic nasopharyngeal carcinoma (NPC). The cost-effectiveness analysis was designed to identify the economic option for metastatic NPC from a Chinese societal perspective. METHODS: We established a Markov model that involved three health states representing the stages of disease to simulate therapy. Survival data of clinical outcomes were derived from the trial and adjusted to quality-adjusted life years (QALYs). Transition probabilities and health utilities were obtained from the clinical trial and published literatures. The cost-effective strategy was estimated for these treatments using a willing-to-pay (WTP) threshold. A one-way sensitivity analysis was conducted to study the influences of parameters. RESULTS: GP treatment group produced a gain of 0.37 QALYs with an incremental cost of $2520.80, yielding an incremental cost-effectiveness ratio (ICER) of $6812.97 per QALY, compared with FP treatment ($15,530.96 versus $13,010.16). The ICER was lower than the accepted WTP threshold, which was 3 times gross domestic product per capita of China ($25,749 per QALY). CONCLUSION: GP regimen is more cost-effective compared with FP regimen as the first-line treatment for Chinese patients with metastatic NPC.

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 Pembrolizumab for Patients with Advanced, Unresectable, or Metastatic Urothelial Cancer Ineligible for Cisplatin-based Therapy.

BACKGROUND: There is an unmet need for effective therapies for patients with advanced or metastatic urothelial cancer who cannot tolerate cisplatin-based chemotherapy. Cisplatin-ineligible patients experience a high frequency of adverse events from the most commonly used standard of care treatment, carboplatin plus gemcitabine, or alternative treatment with gemcitabine monotherapy. Pembrolizumab is a potent, highly selective humanised monoclonal antibody that releases checkpoint inhibition of the immune response system, and provides a new alternative for these patients. OBJECTIVE: To assess the cost-effectiveness of pembrolizumab for first-line treatment of urothelial carcinoma ineligible for cisplatin-based therapy in patients with strongly PD-L1-positive tumours in Sweden. DESIGN, SETTING, AND PARTICIPANTS: Parametric survival curves were fitted to overall survival, progression-free survival, and time on treatment data from KEYNOTE-052 to extrapolate clinical outcomes. A simulated treatment comparison and a network meta-analysis were conducted to estimate the comparative efficacy of pembrolizumab versus carboplatin plus gemcitabine and gemcitabine monotherapy. EQ-5D data from KEYNOTE-052 were used to estimate utility, while resource use and cost inputs were estimated using Swedish regional pricing lists and clinician opinion. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The model reported costs, life years, and quality-adjusted life years (QALYs), and results were tested using deterministic and probabilistic sensitivity analysis. RESULTS AND LIMITATIONS: We estimated that pembrolizumab would improve survival by 2.11 and 2.16 years and increase QALYs by 1.71 and 1.75 compared to carboplatin plus gemcitabine and gemcitabine monotherapy, respectively. Pembrolizumab was associated with a cost increase of €90520 versus carboplatin plus gemcitabine and €95055 versus gemcitabine, with corresponding incremental cost-effectiveness ratios of €53055/QALY and €54415/QALY. CONCLUSIONS: At a willingness-to-pay threshold of €100000/QALY, pembrolizumab is a cost-effective treatment versus carboplatin plus gemcitabine and versus gemcitabine. PATIENT SUMMARY: This is the first analysis to show that pembrolizumab is a cost-effective option for first-line treatment of cisplatin-ineligible patients with locally advanced or metastatic urothelial carcinoma in Sweden.

The economic impact of the transition from branded to generic oncology drugs.

Background: Economic evaluations are an integral component of many clinical trials. Costs used in those analyses are based on the prices of branded drugs when they first enter the market. The effect of genericization on the cost-effectiveness (ce) or cost-utility (cu) of an intervention is unknown because economic analyses are rarely updated using the costs of generic drugs. Methods: We re-examined the ce or cu of regimens previously evaluated in Canadian Cancer Trials Group (cctg) studies that included prospective economic evaluations and where genericization has occurred or is anticipated in Canada. We incorporated the new costs of generic drugs to characterize changes in ce or cu. We also determined acceptable cost levels of generic drugs that would make regimens reimbursable in a publicly funded health care system. Results: The four randomized controlled trials included (representing 1979 patients) were cctg br.10 (early lung cancer, adjuvant vinorelbine-cisplatin vs. observation, n = 172), cctg br.21 (metastatic lung cancer, erlotinib vs. placebo, n = 731), cctg co.17 (metastatic colon cancer, cetuximab vs. best supportive care, n = 557), and cctg ly.12 (relapsed or refractory lymphoma, gemcitabine-dexamethasone-cisplatin vs. cytarabine-dexamethasone-cisplatin, n = 619). Since the initial publication of those trials, the genericization of vinorelbine, erlotinib, cetuximab, and cisplatin has taken place or is expected in Canada. Costs of generics improved the ces and cus of treatment significantly. For example, genericization of erlotinib ($1460.25 per 30 days) resulted in an incremental cost-effectiveness ratio (icer) of $45,746 per life-year gained compared with $94,638 for branded erlotinib. Likewise, genericization of cetuximab ($275.80 per 100 mg) produced an icer of $261,126 per quality-adjusted life-year (qaly) gained compared with $299,613 for branded cetuximab. Decreases in the cost of generic cetuximab to $129.39 and $63.51 would further improve the icer to $150,000 and $100,000 per QALY respectively. Conclusions: Genericization of a costly oncology drug can modify the ce and cu of a regimen significantly. Failure to revisit economic analyses with the costs of generics could be a missed opportunity for funding bodies to optimize value-based allocation of health care resources. At current levels, the costs of generics might not be sufficiently low to sustain publicly funded health care systems.

Managing the economic impact of advanced pancreatic cancer.

Pancreatic cancer is typically diagnosed in the late stage of the disease, making it the fourth leading cause of cancer-related death in the United States. It is also one of the few cancers with an increasing incidence, particularly in the younger population. By 2030, it is expected to become the second leading cause of cancer-related death. Patients with pancreatic cancer encounter monthly medical costs 15 times higher than those without, with costs highest in the later stages of the disease. Treatments for pancreatic cancer include surgery (available to fewer than 20% of newly diagnosed patients) and, for advanced disease, chemotherapy with gemcitabine with nab-paclitaxel or FOLFIRINOX, which can increase overall survival (OS) by a few months. Economic and outcome analyses of clinical data find no significant difference in OS between the 2 regimens, although FOLFIRINOX carries a much higher rate of serious adverse effects, limiting its use to patients with good performance status. In 2017, the FDA approved immunotherapy for patients with microsatellite instability-high or mismatch repair-deficient solid tumors, which occurs in approximately 1% of pancreatic cancer diagnoses. Several immunotherapies and targeted therapies are currently in clinical trials and may significantly alter the trajectory of the disease. However, they typically cost more than $100,000 per year, putting significant strain on payers. Thus, it is important that payers plan now for the potential arsenal of new treatments and identify opportunities to manage their utilization as well as patients with the disease to contain costs.

[Comparative costs study between ready-to-administer bag of gemcitabine and production in reconstitution unit]. / Étude comparative de coûts entre les poches de gemcitabine prêtes à l'emploi et une fabrication en unité de reconstitution.

INTRODUCTION: Dose-banding is needed to rationalise cytotoxic drugs preparations. A new step was recently crossed: gemcitabine is the first molecule to be sold in ready-to-administer bag. What's the pharmaco-economic impact of gemcitabine ready-to-administer bags versus manufacturing in preparation unit? METHODS: A retrospective analysis of gemcitabine dosage prepared over three months permitted to explain our consumption of this drug, and by modelling, to characterize the good prescription interval for each dosage. Compared costs study assessed cost of medicine, preparation kit and preparation time. RESULTS: Over the study period, for 5%, 7.5% and 10% of deviation, respectively 67%, 75% and 76% of preparations were covered by standard doses. We chose 7.5% interval. The manufacturing cost of gemcitabine infusions is around 30,000€/year for vials with solution for infusion, 32,300€ for vials with powder, versus 67,300€ for ready-to-administer bag. Approximately 7.75minutes of pharmacy technician time would be saved by preparation. DISCUSSION: Ready-to-administer bags of gemcitabine allow relevant coverage of manufacturing doses. The annual extra cost would reach 37,200€ for our establishment. But, it can be justified by expected benefits: safer medication circuit, saving time of pharmacy technician….

Economic Evaluation for USA of Systemic Chemotherapies as First-Line Treatment of Metastatic Pancreatic Cancer.

BACKGROUND: Treatments for metastatic pancreatic cancer include monotherapy with gemcitabine (GEM); combinations of GEM with oxaliplatin (OX + GEM), cisplatin (CIS + GEM), capecitabine (CAP + GEM), or nab-paclitaxel (NAB-P + GEM); and the non-GEM combination FOLFIRINOX. Combination therapies have yielded better survival outcomes than GEM alone. A sponsor-independent economic evaluation of these regimens has not been conducted for USA. OBJECTIVE: The objective of this study was to estimate the cost utility and cost effectiveness of these regimens from the payer perspective for USA. METHODS: A three-state Markov model (progression-free, progressed disease, death) simulating the total costs and health outcomes (quality-adjusted life-years; life-years) was developed to estimate the incremental cost-utility and cost-effectiveness ratios. FOLFIRINOX clinical data were obtained from trial and indirect estimates were obtained from network meta-analyses. Lifetime horizon and 3%/year discount rates were used. RESULTS: FOLFIRINOX was the most expensive regimen and GEM the least costly regimen. Compared to GEM, all but one (CIS + GEM) regimen were found to be more effective in quality-adjusted life-years and life-years. Compared to GEM, the incremental cost-utility ratios for CAP + GEM, OX-GEM, NAB-P + GEM, and FOLFIRINOX, were US$180,503, US$197,993, US$204,833, and US$265,718 per additional quality-adjusted life-year, respectively; and the incremental cost-effectiveness ratios were US$88,181, US$87,620, US$135,683, and US$167,040 per additional life-year, respectively. A probabilistic sensitivity analysis confirmed the base-case analysis. CONCLUSIONS: This sponsor-independent economic evaluation for USA found that OX + GEM, CAP + GEM, FOLFIRINOX, and NAB-P + GEM, but not CIS + GEM, were more expensive but also more effective than GEM alone in terms of quality-adjusted life-years and life-years gained. The NAB-P + GEM regimen appears to be the most cost effective in USA at a willingness-to-pay threshold of US$200,000/quality-adjusted life-year.