Immune checkpoint inhibitor combinations for patients with advanced endometrial cancer: a network meta-analysis and cost-utility analysis.

BACKGROUND: Immune checkpoint inhibitor combinations show significant survival advantages compared with chemotherapy for patients with advanced endometrial cancer. OBJECTIVE: To compare the efficacy, safety, and cost-effectiveness of different immunotherapy combinations for clinician and patient decision-making. METHODS: The PubMed, Embase, Cochrane, and Web of Science Databases were reviewed from January 1, 2010 to October 30, 2023, for phase III randomized controlled trials of first-line immunotherapy combinations in patients with advanced endometrial cancer. Bayesian network meta-analysis was performed to obtain hazard ratios (HRs) of overall survival and progression-free survival, relative risks (RRs) of adverse events, and corresponding p value. The lifetime Markov model of cost-effectiveness analysis was developed to summarize the cost, life-years, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios at the US$150 000/QALY of willingness-to-pay of six first-line treatment strategies. RESULTS: Four trials were identified, involving 2577 patients. Dostarlimab plus chemotherapy or durvalumab plus chemotherapy with olaparib was associated with more survival benefits than other immunotherapy regimens and chemotherapy in the mismatch repair-deficient microsatellite instability-high (dMMR/MSI-H) and mismatch repair-proficient microsatellite-stable (pMMR/MSS) population, respectively. Further, pembrolizumab plus chemotherapy versus chemotherapy increased efficacy (cost) by 3.76 QALYs and US$540 817, which yielded incremental cost-effectiveness ratios of US$143 894/QALY in the dMMR/MSI-H population. CONCLUSION: First-line durvalumab plus chemotherapy with olaparib, and dostarlimab plus chemotherapy, were more beneficial for survival in the pMMR/MSS and dMMR/MSI-H populations, respectively. Only pembrolizumab plus chemotherapy versus chemotherapy was cost-effective for patients with dMMR/MSI-H endometrial cancer in the USA.

Treatment-related adverse events of antibody-drug conjugates in clinical trials: A systematic review and meta-analysis.

BACKGROUND: Antibody-drug conjugates (ADCs) have complex molecular structures and have been tested in numerous clinical trials. Therefore, understanding the mechanisms of their toxicity when applied in medical practice is of high importance. METHODS: In a systematic review and meta-analysis of data gathered from different scientific databases (PubMed, Embase, Cochrane, and Web of Science) between January 1, 2000, and June 7, 2022, the authors applied a random-effects model with logit transformation and evaluated the heterogeneity between studies using I2 statistics. The primary outcome was the incidence and 95% confidence interval (CI) for all-grade and grade ≥3 treatment-related adverse events and differences between different drugs, molecular structures, and cancer types. RESULTS: In total, 2511 records were identified that included 169 clinical trials involving 22,492 patients. The overall incidence of treatment-related adverse events was 91.2% (95% CI, 90.7%-91.7%; I2  = 95.9%) for all-grade adverse events and 46.1% (95% CI, 45.2%-47.0%; I2  = 96.3%) for grade ≥3 adverse events. The most common all-grade adverse events were lymphopenia (53.0%; 95% CI, 48.7%-57.3%), nausea (44.1%; 95% CI, 43.2%-44.9%), neutropenia (43.7%; 95% CI, 42.6%-44.9%), blurred vision (40.5%; 95% CI, 37.4%-43.6%), and peripheral neuropathy (39.6%; 95% CI, 38.2%-41.1%); and the most common grade ≥3 adverse events were neutropenia (31.2%; 95% CI, 30.2%-32.3%), hypoesthesia (23.3%; 95% CI, 10.6%-35.9%), thrombocytopenia (22.6%; 95% CI, 21.3%-23.9%), febrile neutropenia (21.2%; 95% CI, 19.3%-23.1%), and lymphopenia (21.0%; 95% CI, 18.2%-23.7%). CONCLUSIONS: Different ADCs appear to affect various treatment-related adverse events and provide comprehensive data on treatment-related adverse events for ADCs. The current results provide an important reference for clinicians and patients on how to care for toxicities from ADCs in clinical practice. LAY SUMMARY: Unique anticancer drugs called antibody-drug conjugates (ADCs) have made significant progress in oncology in recent years because of their great success, and they are rapidly being used in the clinic as well as in hundreds of ongoing trials exploring their further use. The occurrence of serious side effects (adverse events) related to the receipt of ADCs was studied using data from 169 clinical trials involving 22,492 patients to determine the treatment-related causes of higher toxicity and adverse events in patients who receive ADCs, because these data are crucial for informing physicians how to safely treat patients using ADCs. The results indicate that different ADCs appear to affect various adverse events related to their use, providing comprehensive data on these ADCs that provide an important reference for clinicians and patients on how to care for toxicities from ADCs in clinical practice.

Immune checkpoint inhibitor for patients with advanced biliary tract cancer: A cost-effectiveness analysis.

BACKGROUND AND AIMS: The increasingly widespread of immune checkpoint inhibitors (ICIs) in the field of antitumors has brought a new dawn for patients with advanced biliary tract cancer (aBTC). However, the choice of treatment needs to be supported by economic evaluation. Therefore, the cost-effectiveness comparison of first-line durvalumab or pembrolizumab plus gemcitabine and cisplatin (GemCis) treatment of aBTC was explored from the perspective of American and Chinese healthcare systems. METHODS: Ground on the TOPAZ-1 and KEYNOTE-966 trials, the Markov model with a 15-year horizon including three health states to imitate cost and effective outcomes was established. Incremental cost-effectiveness ratio (ICER) at willingness-to-pay (WTP) thresholds of $100 000/QALY and $37 408/ALY in the USA and China was used as the most important indicator. Other endpoint indexes included total cost, life years (LYs), quality-adjusted life years (QALYs) and incremental net-health benefit (INHB). To verify the robustness, sensitivity and subgroup analyses were performed. RESULTS: Durvalumab plus GemCis ($322 211 [2.94 QALYs] and $35 695 [2.76 QALYs]) increased cost (effectiveness) by $63 777 (.22 QALYs) and $5234 (.20 QALYs) than pembrolizumab plus GemCis ($258 434 [2.72 QALYs] and $30 461 [2.56 QALYs]) in the USA and China, respectively. The corresponding ICER was $288 725/QALY and $26 401/QALY, with INHB of -.42 and .06 QALYs, respectively. The cost of ICIs was the most important factor influencing results. CONCLUSIONS: In China, first-line durvalumab plus GemCis versus pembrolizumab plus GemCis was a cost-effective option for patients with aBTC, but not in the USA.

Pembrolizumab plus lenvatinib as first-line therapy for patients with mismatch repair-proficient advanced endometrial cancer: A United States-based cost-effectiveness analysis.

OBJECTIVE: In 2022, the KEYNOTE-775 (NCT03517449) study showed that pembrolizumab plus lenvatinib (PL) has more benefits than traditional chemotherapy as a first-line regimen to treat patients with mismatch repair-proficient (pMMR) advanced endometrial cancer (aEC). However, given the high cost of immuno-targeted therapy, the widespread use among patients remains uncertain. Therefore, we conducted a cost-effectiveness comparison between PL and chemotherapy. METHODS: We evaluated the cost-effectiveness of PL versus chemotherapy over 7 years by developing a comprehensive Markov model, included 697 patients, that calculated total cost, life-years (LYs), quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratio (ICER) at a willingness-to-pay (WTP) threshold of $150,000 per QALY. The robustness of the model was evaluated by one-way, two-way, and probabilistic sensitivity analyses. In addition, we also performed subgroup analyses. RESULTS: Chemotherapy yielded a mean survival of 0.705 QALYs (0.901 LYs) per patient and was associated with a mean cost of $163,777. PL was associated with an incremental cost of $38,582 and an additional 0.349 QALYs, leading to an ICER of $110,401 per QALY as compared to chemotherapy. The cost of pembrolizumab had a significant impact on ICER. At the assumed WTP threshold of $150,000 per QALY, approximately 79.2% of simulations show cost-effectiveness occurs in PL. Results of the subgroup analysis showed that PL was the most cost-effective regimen for patients who had previously received 1-line of therapy. CONCLUSION: For patients with pMMR aEC, the PL strategy may be the most cost-effective strategy at a WTP of $150,000 from the economic perspective of the United States.

Cost-Effectiveness of Pembrolizumab plus Axitinib Versus Sunitinib as First-Line Therapy in Advanced Renal Cell Carcinoma in the U.S.

BACKGROUND: The data from the phase III clinical trial KEYNOTE-426 indicated that pembrolizumab plus axitinib compared with sunitinib could generate clinical benefits in patients with previously untreated advanced renal cell carcinoma (RCC). Given the incremental clinical benefits, we examined the potential cost-effectiveness of pembrolizumab plus axitinib versus sunitinib in the first-line setting for patients with advanced RCC from the U.S. payers' perspective. MATERIALS AND METHODS: Cost and health outcomes were estimated at a willingness-to-pay (WTP) threshold of $100,000 to $150,000 per quality-adjusted life-year (QALY). One-way and probabilistic sensitivity analyses were performed by varying potentially modifiable parameters, and additional subgroup analyses were performed as well. RESULTS: Upon our analyses, the total treatment costs in the pembrolizumab plus axitinib and sunitinib groups were $522,796 and $348,424 and the QALYs gained 2.90 and 1.72, respectively. In the base-case analysis, compared with receiving sunitinib, patients with advanced RCC receiving pembrolizumab plus axitinib gained 1.18 more QALYs at an incremental cost-effectiveness ratio of $148,676/QALY. The results of subgroup analyses demonstrated that pembrolizumab plus axitinib was most cost-effective for patients who had one organ with metastasis. CONCLUSION: First-line treatment with pembrolizumab plus axitinib, compared with sunitinib, is a cost-effective strategy when the value of WTP is from $100,000 to $150,000 per QALY in patients with advanced RCC. For patients with one-organ metastasis and those in International Metastatic Renal Cell Carcinoma Database Consortium poor risk group, first-line treatment with pembrolizumab plus axitinib is more cost-effective than others. IMPLICATIONS FOR PRACTICE: This was the first study to examine the cost-effectiveness of pembrolizumab plus axitinib versus sunitinib in advanced renal cell carcinoma (RCC). This study found that first-line treatment with pembrolizumab plus axitinib is a cost-effective strategy when the value of willingness-to-pay is from $100,000 to $150,000 per quality-adjusted life-year in patients with advanced RCC from the U.S. payers' perspective.

Cost-Effectiveness Analysis of Durvalumab Plus Chemotherapy in the First-Line Treatment of Extensive-Stage Small Cell Lung Cancer.

BACKGROUND: In the CASPIAN trial, durvalumab + chemotherapy demonstrated significant improvements in overall survival compared with chemotherapy alone in patients with extensive-stage small cell lung cancer (SCLC). We aimed to assess the cost-effectiveness of durvalumab in patients with extensive-stage SCLC from the US healthcare system perspective. PATIENTS AND METHODS: A comprehensive Markov model was adapted to evaluate cost and effectiveness of durvalumab combination versus platinum/etoposide alone in the first-line therapy of extensive-stage SCLC based on data from the CASPIAN study. The main endpoints included total costs, life years (LYs), quality-adjusted life-years (QALYs), and incremental cost-e-ectiveness ratios (ICERs). Model robustness was assessed with sensitivity analysis, and additional subgroup analyses were also performed. RESULTS: Durvalumab + chemotherapy therapy resulted in an additional 0.27 LYs and 0.20 QALYs, resulting in an ICER of $464,711.90 per QALY versus the chemotherapy treatment. The cost of durvalumab has the greatest influence on this model. Subgroup analyses showed that the ICER remained higher than $150,000/QALY (the willingness-to-pay threshold in the United States) across all patient subgroups. CONCLUSIONS: Durvalumab in combination with platinum/etoposide is not a cost-effective option in the first-line treatment of patients with extensive-stage SCLC.

First-line pembrolizumab plus chemotherapy for extensive-stage small-cell lung cancer: a United States-based cost-effectiveness analysis.

BACKGROUND: The clinical trial of Keynote-604 showed that pembrolizumab plus chemotherapy could generate clinical benefits for extensive-stage small-cell lung cancer (ES-SCLC). We aim to assess the efficacy and cost of pembrolizumab combined with chemotherapy in the first-line treatment setting of ES-SCLC from the United States (US) payers' perspective. METHODS: A synthetical Markov model was used to evaluate cost and effectiveness of pembrolizumab plus platinum-etoposide(EP) versus EP in first-line therapy for ES-SCLC from the data of Keynote-604. Lifetime costs life-years(LYs), quality adjusted LYs(QALYs) and incremental cost-effectiveness ratios(ICERs) were estimated. One-way and probabilistic sensitivity analyses were performed. Furthermore, we performed subgroup analysis. RESULTS: Pembrolizumab plus EP resulted in additional 0.18 QALYs(0.32 LYs) and corresponding incremental costs $113,625, resulting an ICER of $647,509 per QALY versus EP. The price of pembrolizumab had a significant impact on ICER. Probabilistic sensitivity analysis indicated that pembrolizumab combined chemotherapy may become a cost-effective option with a probability of 0%. Besides, subgroup analysis suggested that all subgroups were not cost-effective. CONCLUSION: From the perspective of the US payer, pembrolizumab plus EP is not a cost-effective option for first-line treatment patients with ES-SCLC at a WTP threshold of $150,000 per QALY.

Immunotherapy plus chemotherapy in patients with advanced endometrial cancer: a cost-effectiveness analysis.

OBJECTIVE: Pembrolizumab and dostarlimab are immune checkpoint inhibitors that target programmed death receptor 1 (PD-1). Combination anti-PD-1 regimens have been shown to exhibit favorable survival benefits when treating advanced endometrial cancer (EC). Which treatment was preferable will need to be confirmed by a cost-effectiveness comparison between them. METHODS: Based on patient and clinical parameters from RUBY and NRG-GY018 phase III randomized controlled trials, the Markov model with a 20-year time horizon was established to evaluate the cost-effectiveness of dostarlimab plus chemotherapy (DC), pembrolizumab plus chemotherapy (PC), and chemotherapy alone (C) treatment for patients with mismatch repair-proficient microsatellite-stable (pMMR-MSS) and mismatch repair-deficient microsatellite instability-high (dMMR-MSI-H) advanced EC from the American payers' perspective. The main results include total cost, life-years (LYs), quality-adjusted life-years (QALYs), and the incremental cost-effectiveness ratio (ICER) at a $150,000/QALY of willingness-to-pay. RESULTS: In the pMMR-MSS population, DC, PC, and C produced costs (QALYs) of $99,205 (3.02), $322,530 (3.25), and $421,923 (4.40), resulting in corresponding ICERs of $974,177/QALY (PC vs. C), $234,527/QALY (DC vs. C), $86,671/QALY (DC vs. PC), respectively; In the dMMR-MSI-H population, DC, PC, and C obtained costs (QALYs) of $120,177 (5.73), $691,399 (8.43), and $708,787 (11.26), yielding ICERs of $266,423/QALY (PC vs. C), $135,165/QALY (DC vs. C), $7,866/QALY (DC vs. PC), respectively. CONCLUSION: In the US, DC was a more cost-effective treatment than PC for patients with advanced EC irrespective of MMR status. However, compared to C, DC was associated with more cost-effectiveness in the dMMR-MSI-H population.

TAS-102 with or without bevacizumab treatment for patients with metastatic colorectal cancer: a multi-country cost-effectiveness analysis.

Background: TAS-102 (trifluridine/tipiracil) plus bevacizumab demonstrated a significant survival benefit in patients with refractory metastatic colorectal cancer (mCRC). Physicians and patients are uncertain whether this treatment option is clinically acceptable in different countries, underscoring the need for analyses of the cost-effectiveness of this regimen. Objectives: To guide doctors and patients to choose TAS-102 plus bevacizumab or TAS-102 monotherapy in cancer treatment. Design: The cost-effective analysis. Methods: A comprehensive Markov model of the 10-year horizon for three health states was established using data from the SUNLIGHT trial to evaluate the cost and health effects of TAS-102 with or without bevacizumab at particular willingness-to-pay (WTP) thresholds, analyzing parameters including quality-adjusted life-years (QALYs), incremental cost-effectiveness ratios (ICERs), incremental net monetary benefit, as well as incremental net-health benefit (INHB). Sensitivity and subgroup analyses were additionally conducted. Results: Treatment with TAS-102 plus bevacizumab versus TAS-102 monotherapy increased effectiveness (cost) by 0.39 ($151,474), 0.38 ($26,794), and 0.41 ($8596) QALYs, with an ICER of $388,171, $69,617, and $20,919 per QALY and an INHB of -0.62, -0.03, and 0.18 QALYs in the United States, United Kingdom, and China, respectively. The utility of progression-free survival was the most important factor in this model. At respective WTP thresholds of $150,000, $65,000, and $37,653 per QALY in the United States, United Kingdom, and China, the odds of TAS-102 plus bevacizumab being the dominant treatment were 0%, 49.6%, and 87.8%, respectively. In addition, mCRC patients with an Eastern Oncology Cooperative Group performance status ⩾ 1 may be the best candidates for treatment. Conclusion: TAS-102 plus bevacizumab treatment represents a cost-effective third-line treatment for refractory mCRC from a Chinese payers' perspective, although the same was not true in the United States or United Kingdom at current drug prices.

TAS-102-bevacizumab for metastatic colorectal cancer TAS-102 plus bevacizumab treatment represents a cost-effective third-line treatment for refractory metastatic colorectal cancer in China, although the same was not true in the US or UK at current drug prices.

Combination tumor-treating fields treatment for patients with metastatic non-small cell lung cancer: A cost-effectiveness analysis.

BACKGROUND: Tumor-treating field (TTFields) was a novel antitumor therapy that provided significant survival for previously treated metastatic non-small cell lung cancer (mNSCLC). The consistency of the cost of the new treatment regimen with its efficacy was the main objective of the study. METHODS: The primary parameters, derived from the Phase 3 LUNAR study, were collected to evaluate the cost and efficacy of TTFields plus standard-of-care (SOC) (immune checkpoint inhibitors [ICIs] and docetaxel [DTX]) or SOC in patients with mNSCLC by establishing a three-state Markov model over a 15-year time horizon. Primary outcome measures for this study included costs, life-years (LYs), quality-adjusted LYs (QALYs), and incremental cost-effectiveness ratios (ICERs). Sensitivity analyses were performed. RESULTS: The total costs of TTFields plus SOC, TTFields plus ICI, and TTFields plus DTX were $319,358, $338,688, and $298,477, generating 1.23 QALYs, 1.58 QALYs, and 0.89 QALYs, respectively. The ICERs of TTFields plus SOC versus SOC, TTFields plus ICI versus ICI, and TTFields plus DTX versus DTX were $613,379/QALY, $387,542/QALY, and $1,359,559/QALY, respectively. At willingness-to-pay (WTP) thresholds of $150,000/QALY, the probability of combination TTFields being cost-effective was 0%. In addition, TTFields plus SOC exhibited similar efficacy (1.12 QALYs and 1.14 QALYs) and costs ($309,822 and $312,531) in the treatment of squamous cell carcinoma (SCC) and non-squamous cell carcinoma (NSCC) populations. CONCLUSIONS: In the United States, TTFields plus SOC as second-line treatment was not a more cost-effective strategy for patients with mNSCLC. Of the analyzed regimens, TTFields plus ICI was associated with most significant health benefits.

Mirvetuximab soravtansine in platinum-resistant recurrent ovarian cancer with high folate receptor-alpha expression: a cost-effectiveness analysis.

OBJECTIVE: Mirvetuximab soravtansine (MIRV), a new antibody-drug conjugate, versus the investigator's choice of chemotherapy (IC) was the first treatment to demonstrate benefits for progression-free and overall survival in platinum-resistant recurrent ovarian cancer (PROC) with high folate receptor-alpha (high-FRα) expression. Efficacy, safety, and economic effectiveness make MIRV the new standard of care for these patients. METHODS: Based on patients and clinical parameters from MIRASOL (GOG 3045/ENGOT-ov55) phase III randomized controlled trials, the Markov model with a 20-year time horizon was established to evaluate the cost and efficacy of MIRV and IC for PROC with high-FRα expression, considering the bevacizumab-pretreated situation from the American healthcare system. Total cost, life-years (LYs), quality-adjusted life-years (QALYs), incremental cost-effectiveness ratio (ICER), and incremental net health benefits were the main outcome indicators and compared with willingness-to-pay threshold of $100,000/QALY. Sensitivity and scenario analyses were conducted. RESULTS: Compared with the IC, MIRV was associated with incremental costs of $538,251, $575,674, and $188,248 with the corresponding QALYs (LYs) increased by 0.90 (1.55), 1.09 (1.88), and 0.53 (0.79), leading to ICERs of $596,189/QALY ($347,995/LY), $530,061/QALY ($306,894/LY), and $1,011,310/QALY ($680,025/LY) in the overall, bevacizumab-naïve, and bevacizumab-pretreated patients, respectively. When MIRV is reduced by more than 75%, it may be a cost-effective treatment. CONCLUSION: At the current price, MIRV for PROC with high-FRα expression is not the cost-effective strategy in the US. However, its treatment has higher health benefits in bevacizumab-naïve patients, which is likely to be an alternative.

Chemoradiotherapy plus immunotherapy for locoregionally advanced nasopharyngeal carcinoma: A cost-effectiveness analysis.

BACKGROUND: Research focused on the addition of immune checkpoint inhibitors (ICIs) to radiotherapeutic regimens in patients with cancer has become increasingly common, revealing promising improvements in efficacy outcomes. In patients with locoregionally advanced nasopharyngeal carcinoma (NPC), combining immunotherapy with chemoradiotherapy can facilitate the significant prolongation of survival, emphasizing the need for pharmacoeconomic studies focused on the clinical uptake of these innovative treatment regimens. METHODS: A three-state Markov model was developed based on clinical data from the randomized phase 3 CONTINUUM trial and used to compare the cost-effectiveness of chemoradiotherapy plus sintilimab (sintilimab group) to chemoradiotherapy alone (standard group), analyzing outcomes including incremental cost-effectiveness ratio (ICER), incremental net monetary benefit (INMB), and incremental net-health benefit (INHB) values at a willingness-to-pay (WTP) threshold corresponding to three times the Chinese GDP per capita ($37 035 per quality-adjusted life year [QALY]). RESULTS: The total costs for patients in the sintilimab and standard groups (QALYs [LYs]) were $92 116 (6.68 [10.03]) and $53 255 (3.75 [5.55]), respectively, for an ICER of $13 230/QALY ($8672/LY), an INMB of $70 021 with INHB of 1.89 QALYs. Using the selected WTP threshold. On the standard WTP threshold, the prevalence of sintilimab group as the primary treatment was 90.55% in China. The establishment of the model is stable. CONCLUSIONS: Adding sintilimab to chemoradiotherapeutic regimens represents an innovative and cost-effective means for patients with locoregionally advanced NPC management in China.

Olaparib plus bevacizumab as a first-line maintenance treatment for patients with advanced ovarian cancer by molecular status: an updated PAOLA-1 based cost-effectiveness analysis.

OBJECTIVE: The PAOLA-1 trial (NCT02477644) reported final survival benefit associated with olaparib plus bevacizumab maintenance treatment of patients with advanced ovarian cancer (AOC) based on molecular status. Our aimed to compare the cost-effectiveness of olaparib plus bevacizumab for overall patients, patients with a breast cancer susceptibility genes (BRCA) mutation, homologous recombination deficiency (HRD), or HRD without BRCA mutations AOC from the context of the American healthcare system. METHODS: Analysis of health outcomes in life-years (LYs), quality-adjusted life-years (QALYs), and the incremental cost-effectiveness ratio (ICER) in various molecular status-based AOC patient at a $150,000/QALY of willingness-to-pay was performed using a state-transitioned Markov model with a 20-year time horizon. Meanwhile, sensitivity analyses assessments were also used to gauge the model's stability. RESULTS: The ICERs of olaparib plus bevacizumab versus bevacizumab alone were $487,428 ($374,758), $249,579 ($191,649), $258,859 ($198,739), and $270,736 ($206,640) per QALY (LY) in the overall patients, patients with BRCA mutations, patients with HRD, and patients with HRD without BRCA mutations AOC, respectively, which indicated that The ICERs was higher than $150,000/QALY in the US. Progression-free survival (PFS) value and olaparib cost emerged as the primary influencing factors of these findings in the sensitivity analysis. CONCLUSION: At current cost levels, olaparib plus bevacizumab treatment is not a cost-effective treatment for patients with AOC regardless of their molecular status in the US. However, this maintenance treatment may be more favorable health advantages for patients with BRAC mutations AOC.

Adverse events of biologic or small molecule therapies in clinical trials for inflammatory bowel disease: A systematic review and meta-analysis.

Background: Biologic or small-molecule therapies are highly effective for the treatment of inflammatory bowel disease (IBD), and approval by the FDA has significantly increased both their clinical use and the development of novel regimens. However, the identification and management of their associated toxicities poses challenges for clinicians and researchers. Methods: A systematic review and meta-analysis of randomized controlled trials (RCTs) published from January 1, 2000, to October 15, 2022, and in the databases. A random-effects model with logit transformation was applied to the analysis heterogeneity between studies was evaluated using the I2 statistic with incidence and 95 % confidence interval (CI) for any adverse events (AEs), and serious AEs (SAEs). Results: In Crohn's disease (CD), the total AE incidence was 67.0 % (95 % CI, 66.2%-67.8 %; I2 = 97.2 %) for any AEs and 7.3 % (6.9-7.7; 97.2) for serious AEs. In ulcerative colitis (UC), the overall incidence of any and serious AEs was 63.6 % (63.0-64.3; 98.1) and 5.7 % (5.4-6.0; 88.9), respectively. The most common AEs were infections (21.5 [20.3-22.8], 32.6 [31.0-34.2], 25.9 [24.5-27.2], and 13.7 [10.7-16.7]) in CD patients that were treated with TNF antagonists, anti-integrins, anti-IL agents, and JAK inhibitors, respectively, and in UC patients also were infections (22.8 [21.7-24.0], 27.4 [25.9-28.9], and 18.4 [16.7-20.2]), respectively, as well as increases in lactic dehydrogenase levels (23.1 [20.8-25.4]) with JAK inhibitors. Conclusion: This study offers a comprehensive summary of toxic side effects of IBD treatments and a useful reference for both patients and clinicians.

First-Line Lenvatinib Plus Pembrolizumab or Everolimus versus Sunitinib for Advanced Renal Cell Carcinoma: A United States-Based Cost-Effectiveness Analysis.

INTRODUCTION: The CLEAR trial indicated that survival benefits were generated with lenvatinib plus pembrolizumab (LP) or everolimus (LE) than with sunitinib for advanced renal cell carcinoma (aRCC). However, the high cost of immuno-target and dual-targeted treatment, we assessed the cost-effectiveness of lenvatinib plus pembrolizumab or everolimus in the first-line setting for treatment of patients with aRCC from the United States (US) payers' perspective. MATERIALS AND METHODS: A comprehensive Markov model was developed to evaluate the cost and effectiveness of LP or LE in first-line therapy for aRCC. We estimated life years (LYs), quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs). Utility values and direct costs related to the treatments were gathered from the published studies. Then, one-way and probabilistic sensitivity analyses were performed. Additional subgroup analyses were considered. RESULTS: Treatment with LP and LE provided an additional 0.67 QALYs (0.62 LYs) and 0.66 QALYs (0.90 LYs) compared with sunitinib, resulting in ICER of $131,656 per QALY and 201,928 per QALY, respectively. The most influential factor in this model was the cost of pembrolizumab with LP. Probabilistic sensitivity analysis showed there was a 58.97% and 28.91% probability that LP and LE were cost-effective at WTP values of $150,000 per QALY in the US. Subgroup analyses demonstrated that LP was more cost-effective for patients from Western Europe and North America, intermediate risk of the International risk group of Metastatic Renal Cell Carcinoma Database Consortium (IMDC), favorable and intermediate risk group of Memorial Sloan Kettering Cancer Center (MSKCC) and PD-L1 combined positive score greater than or equal to 1%. CONCLUSION: From the perspective of the US payer, LP is a cost-effective option as first-line treatment for patients with aRCC at a WTP threshold of $150,000 per QALY, but LE is the opposite.

Cemiplimab as Second-Line Therapy for Patients with Recurrent Cervical Cancer: A United States-based Cost-effectiveness Analysis.

INTRODUCTION: The efficacy of cemiplimab in recurrent cervical cancer has been demonstrated in the clinical trial EMPOWER-Cervical 1. However, its high price makes patients and clinicians hesitate to use it. Therefore, we designed a study to evaluate its cost-effectiveness. METHODS: We developed a Markov model based on phase III clinical trials to calculate the cost, life years (LYs), quality-adjusted life years (QALYs), and incremental cost-effectiveness ratio (ICER) over 20 years with a willingness-to-pay (WTP) threshold of $150,000/QALY. The economic data included were obtained from official US government websites and published literature. Sensitivity analysis was used to determine the uncertainties associated with the model, and a subgroup analysis was performed. RESULTS: Compared with chemotherapy, cemiplimab produced an additional 0.597 QALYs (0.751 LYs), resulting in an ICER of $111,211.471/QALY in the United States. The cost of cemiplimab is the most influential factor in the model. The results of these models were robust in all sensitivity analyses. From the American public payers' perspective, subgroup analysis showed cemiplimab was a cost-effective regimen in patients with squamous cell carcinoma, adenocarcinoma, or programmed cell death ligand 1 (PD-L1) ≥ 1%. CONCLUSION: From the American public payers' perspective, cemiplimab is a cost-effective treatment option for second-line treatment of recurrent cervical cancer. Meanwhile, cemiplimab was a cost-effective treatment for patients with PD-L1 ≥ 1 and all histological types.

The cost-effectiveness analysis of maintenance olaparib plus Bevacizumab in patients with advanced ovarian cancer: based on the final survival results from PAOLA-1 trial.

INTRODUCTION: In 2023, the final PAOLA-1 trial (NCT02477644) survival data were published documenting the benefits of therapy consisting of olaparib plus bevacizumab for patients with advanced ovarian cancer (AOC) as a function of molecular status. In light of these new data, the present study was conducted with the goal of evaluating the cost-effectiveness of olaparib plus bevacizumab for the treatment of the overall AOC patient population and for homologous recombination deficiency (HRD)-positive patients, patients with a breast cancer susceptibility gene (BRCA) mutations, homologous recombination proficiency (HRD)-positive, or patients not harboring BRCA mutations AOC from a US payers perspective. METHODS: A Markov state-transition model with a 15-year time horizon was used to evaluate outcomes of patients administered Olaparib plus bevacizumab versus bevacizumab. Life-years (LYs), quality-adjusted LYs (QALYs), and the incremental cost-effectiveness ratio (ICER) values were evaluated in this study in light of a $150,000/QALY of willingness-to-pay (WTP) threshold. The stability of the established model was evaluated through sensitivity analyses. RESULTS: Relative to bevacizumab alone, Olaparib plus bevacizumab was associated with mean incremental costs and QALYs (LYs) of olaparib plus bevacizumab versus bevacizumab were $293,656 and 1.85 (2.16), $265,668 and 3.34 (4.02), $242,746 and 1.71 (2.06), and $193,792 and 0.97 (1.14) for overall, BRCA mutation-positive, HRD-positive, and HRD-positive BRCA mutation-negative AOC patients, respectively. The corresponding ICER values for these patient subgroups were $158,729 ($136,218), $79,434 ($66,120), $141,636 ($117,747), and $200,595 ($169,733) per QALY (LY) gained Utility value and the price of olaparib were identified in sensitivity analyses as the primary factors influencing these results. CONCLUSION: At current pricing levels, maintenance treatment with olaparib plus bevacizumab treatment may represent a cost-effective therapeutic option for BRCA mutations and HRD-positive AOC patients in the USA.

Immune checkpoint inhibitors plus chemotherapy for HER2-negative advanced gastric/gastroesophageal junction cancer: a cost-effectiveness analysis.

Background: Nivolumab plus chemotherapy (NC) was recently approved as the first-line intervention for human epidermal growth factor receptor 2-negative advanced gastric/gastroesophageal junction cancer (GC/GEJC). Moreover, in the latest KEYNOTE-859 (NCT03675737), pembrolizumab plus chemotherapy (PC) was demonstrated to produce remarkable patient survival outcomes. Objectives: The clinicians and patients need to assess NC and PC preference for cancer drugs. Design: The cost-effective analysis. Methods: In an economic assessment of the United States, United Kingdom, and Chinese healthcare systems using a Markov model simulated patients with GC/GEJC, two treatment decision branches with three health states and a tracked time horizon of 15 years were developed. The overall cost and efficacy outcomes of first-line strategies PC and NC were evaluated at willingness-to-pay (WTP) thresholds of different national, including life-years (LYs), quality-adjusted life-years (QALYs), incremental cost-effectiveness ratios (ICERs), and incremental net-health benefit (INHB). Sensitivity and subgroup analyses were considered. Results: Given a WTP threshold of $150,000, $60,161, and $37,653 per QALY in the United States, United Kingdom, and China, respectively, both PC and NC achieved QALYs of 1.67 and 1.65 (2.51 and 2.48 LYs), 1.65 and 1.63 (2.48 and 2.45 LYs), and 1.60 and 1.58 (2.40 and 2.37 LYs), with total costs of $242,444 and $232,617, $148,367 and $127,737, and $16,693 and $24,016, respectively. Based on our sensitivity analysis, the programmed death-1 inhibitors cost produced the largest impact on the outcome. In addition, the cost-effectiveness probabilities of PC were 38.3%, 4.1%, and 100% in the three aforementioned countries, respectively. Conclusion: In the case of the Chinese payers' perspective, PC appeared more dominant as first-line therapy for advanced GC/GEJC patients, whereas NC was preferred in the United States and United Kingdom.

Comparative efficacy and safety of novel immuno-chemotherapy for extensive-stage small-cell lung cancer: a network meta-analysis of randomized controlled trial.

Background: Recently, several new first-line immune checkpoint inhibitors (ICIs) plus chemotherapy have been approved for patients with extensive-stage small-cell lung cancer (ES-SCLC). However, direct comparisons between first-line treatments are lacking. Therefore, we indirectly compared the efficacy and safety of specific treatment strategies to inform physicians' and patients' clinical decisions. Methods: The Pubmed, Cochrane, Embase, and Web of Science databases were searched from 1 January 2000 to 27 November 2022, for randomized clinical trials (RCTs) assessing first-line immuno-chemotherapies for ES-SCLC. A fixed-effect multivariable meta-regression model was established for frequentist network meta-analysis and hazard ratios (HRs) with 95% confidence intervals (95% CI) were computed to compare the effects of immuno-chemotherapies on patient overall survival (OS) and progression-free survival (PFS), while risk ratios with 95% CI were used for treatment- and immune-related adverse events (AEs). The p score values were then used to rank treatments based on their odds of being the best treatment option. The research protocol was registered with the PROSPERO (CRD42022383254). Results: Seven studies involving 3822 patients were eligible for analysis. Serplulimab plus chemotherapy had better OS outcomes compared to chemotherapy (HR = 0.63; 95% CI: 0.49-0.82) and ipilimumab plus chemotherapy (HR = 0.67; 95% CI: 0.50-0.90). It additionally exhibited better PFS outcomes compared to chemotherapy (HR = 0.48; 95% CI: 0.39-0.60), adebrelimab (HR = 0.72; 95% CI: 0.53-0.97), atezolizumab (HR = 0.62; 0.46-0.85), durvalumab (HR = 0.60; 95% CI: 0.45-0.80), durvalumab and tremelimumab (HR = 0.57; 95% CI: 0.43-0.76), ipilimumab (HR = 0.57; 95% CI: 0.44-0.73), and pembrolizumab (HR = 0.64; 95% CI: 0.48-0.86) plus chemotherapy. Serplulimab plus chemotherapy was linked to the greatest odds of effectively reducing the odds of death (p score = 0.87) and progression (p score = 0.99) while exhibiting a good safety profile. Conclusion: Serplulimab plus chemotherapy exhibited the best survival outcomes with manageable AEs. Thus, serplulimab plus chemotherapy may represent the optimal best first-line treatment option for ES-SCLC patients.

First-line Immuno-chemotherapy for extensive-stage small-cell lung cancer: A network meta-analysis and cost-effectiveness analysis.

Introduction: Many randomized controlled trials have indicated that immuno-chemotherapy could generate clinical benefits, though the cost of immuno-chemotherapy was so prohibitive and the options were varied. This investigation aimed at evaluating effectiveness, safety, and cost-effectiveness for immuno-chemotherapy as a first-line therapeutic option for ES-SCLC patients. Methods: Multiple scientific literature repositories were searched for clinical studies where immuno-chemotherapy was regarded as the first-line treatment for ES-SCLC, which were published in English between Jan 1, 2000, and Nov 30, 2021. This study conducted a network meta-analysis (NMA) and cost-effectiveness analysis (CEA) based upon US-resident payer perspectives. Overall survival (OS), progression-free survival (PFS), and adverse events (AEs) were evaluated through NMA. In addition, costings, life-years (LYs), quality-adjusted life-years (QALYs), and incremental cost-benefit ratio (ICER) were estimated by CEA. Results: We identified 200 relevant search records, of which four randomized controlled trials (RCTs) (2,793 patients) were included. NMA demonstrated that the effect of atezolizumab plus chemotherapy was ranked at a more elevated position in comparison to other immuno-chemotherapy options and chemotherapy alone, within the general population. The influence of atezolizumab plus chemotherapy and durvalumab plus chemotherapy was ranked higher within populations experiencing non-brain metastases (NBMs) andbrain metastases (BMs), respectively. The CEA revealed that the ICERs of immuno-chemotherapy over chemotherapyalone were higher than the willingness-to-pay (WTP) threshold of $150,000/QALY in any population. However, treatment with atezolizumab plus chemotherapy and durvalumab plus chemotherapy were more favorable health advantages than other immuno-chemotherapy regimens and chemotherapy alone, and the results were 1.02 QALYs and 0.89 QALYs within overall populations and populations with BMs, respectively. Conclusion: The NMA and cost-effectiveness investigation demonstrated that atezolizumab plus chemotherapy could be an optimal first-line therapeutic option for ES-SCLC when compared with other immuno-chemotherapy regimens. Durvalumab plus chemotherapy is likely to be the most favorable first-line therapeutic option for ES-SCLC with BMs.