Academic Journal
View in EDS
PDF Full Text
HTML Full Text

Cost-effectiveness analysis of nimotuzumab combined with gemcitabine for K-Ras wild type locally advanced or metastatic pancreatic cancer in China

Bibliographic Details
Title: Cost-effectiveness analysis of nimotuzumab combined with gemcitabine for K-Ras wild type locally advanced or metastatic pancreatic cancer in China
Authors: Rong Long, Hao Guo, Kun Chen
Source: Scientific Reports, Vol 15, Iss 1, Pp 1-9 (2025)
Publisher Information: Nature Portfolio, 2025.
Publication Year: 2025
Collection: LCC:Medicine
LCC:Science
Subject Terms: K-Ras wild type, Locally advanced or metastatic pancreatic cancer, Nimotuzumab, Gemcitabine, Cost-effectiveness, First-line treatment, Medicine, Science
More Details: Abstract The phase III NOTABLE trial has revealed that nimotuzumab plus gemcitabine achieves greater clinical benefit in the first-line treating K-Ras wild type locally advanced (LA) or metastatic pancreatic cancer (mPC), compared to gemcitabine. Hence, herein, we examined the cost-efficiency of introducing nimotuzumab to gemcitabine, relative to gemcitabinealone, in first-line K-Ras wild type LA or mPC therapy from a Chinese payer perspective. We generated an exhaustive decision-analytical Markov model using three exclusive health states to incorporate both clinical and economic consequences of nimotuzumab plus gemcitabine versus gemcitabine alone as first-line therapy patients with K-Ras wild type LA or mPC. Using a 10-year lifetime horizon, we assessed the total medical expenditure, quality-adjusted life years (QALYs), and incremental cost‒effectiveness ratio (ICER) as the primary surrogate outcomes of our model. Sensitivity analyses were conducted via alteration of internally tweakable parameters, and further subgroup analyses were conducted as needed. The overall health surrogate outcomes were 2.94 QALYs ($215,799) among patients with nimotuzumab plus gemcitabine and 1.83 QALYs ($86,039) among patients with gemcitabine alone (ICER value, $117,263/QALY; Incremental net health benefit [INHB] value, − 2.46/QALY). Based on our sensitivity analysis, among all parameters, progression-free survival (PFS) utility was of utmost importance, and it exerted a considerable impact on our model. The ICER consistently well exceeded the willingness-to-pay (WTP) threshold and negative INHBs were observed across all patient subcategories with zero alteration recorded as cost-effective in the subgroup analyses. Nimotuzumab plus gemcitabine, relative to gemcitabine alone, is not a cost-effective first-line treatment among patients with K-Ras wild type LA or mPC at the current prices offered in China.
Document Type: article
File Description: electronic resource
Language: English
ISSN: 2045-2322
Relation: https://doaj.org/toc/2045-2322
DOI: 10.1038/s41598-025-90960-x
Access URL: https://doaj.org/article/9f472f9a4b074ff5ae8d95d9ac1c8e58
Accession Number: edsdoj.9f472f9a4b074ff5ae8d95d9ac1c8e58
Database: Directory of Open Access Journals
Full text is not displayed to guests.
FullText Links:
  – Type: pdflink
    Url: https://content.ebscohost.com/cds/retrieve?content=AQICAHjPtM4BHU3ZchRwgzYmadcigk49r9CVlbU7V5F6lgH7WwGMY_bqPMzfRVVFQD7RH3F-AAAA4jCB3wYJKoZIhvcNAQcGoIHRMIHOAgEAMIHIBgkqhkiG9w0BBwEwHgYJYIZIAWUDBAEuMBEEDKKNyYEQ3em2rjKkcgIBEICBmmUozeWAFkej7RU6zmXdjKXkN9Td7aPbbTMsw5IzQ9LRLd30zPmh6QXAwXDY9jo9iuBfLsfp8viQFpOpnY2wxKnNm4Q72_kI0SplY2mJAU_Wxj3SpL43w0AeAtpxVBkfitcd3O_J8Xj9Zai52r23pi443EyAXfmJ3p1TYqTYkMU2u7_NqkpDzpcSprS2PSJpQhkHTyHW7irGuUQ=
Text:
  Availability: 1
  Value: <anid>AN0183309807;[fkqs]21feb.25;2025Mar01.13:07;v2.2.500</anid> <title id="AN0183309807-1">Cost-effectiveness analysis of nimotuzumab combined with gemcitabine for K-Ras wild type locally advanced or metastatic pancreatic cancer in China </title> <sbt id="AN0183309807-2">Introduction</sbt> <p>The phase III NOTABLE trial has revealed that nimotuzumab plus gemcitabine achieves greater clinical benefit in the first-line treating K-Ras wild type locally advanced (LA) or metastatic pancreatic cancer (mPC), compared to gemcitabine. Hence, herein, we examined the cost-efficiency of introducing nimotuzumab to gemcitabine, relative to gemcitabinealone, in first-line K-Ras wild type LA or mPC therapy from a Chinese payer perspective. We generated an exhaustive decision-analytical Markov model using three exclusive health states to incorporate both clinical and economic consequences of nimotuzumab plus gemcitabine versus gemcitabine alone as first-line therapy patients with K-Ras wild type LA or mPC. Using a 10-year lifetime horizon, we assessed the total medical expenditure, quality-adjusted life years (QALYs), and incremental cost‒effectiveness ratio (ICER) as the primary surrogate outcomes of our model. Sensitivity analyses were conducted via alteration of internally tweakable parameters, and further subgroup analyses were conducted as needed. The overall health surrogate outcomes were 2.94 QALYs ($215,799) among patients with nimotuzumab plus gemcitabine and 1.83 QALYs ($86,039) among patients with gemcitabine alone (ICER value, $117,263/QALY; Incremental net health benefit [INHB] value, − 2.46/QALY). Based on our sensitivity analysis, among all parameters, progression-free survival (PFS) utility was of utmost importance, and it exerted a considerable impact on our model. The ICER consistently well exceeded the willingness-to-pay (WTP) threshold and negative INHBs were observed across all patient subcategories with zero alteration recorded as cost-effective in the subgroup analyses. Nimotuzumab plus gemcitabine, relative to gemcitabine alone, is not a cost-effective first-line treatment among patients with K-Ras wild type LA or mPC at the current prices offered in China.</p> <p>Considering the sizeable mortality (<reflink idref="bib466" id="ref1">466</reflink>,000) and case (<reflink idref="bib496" id="ref2">496</reflink>,000) incidences worldwide, pancreatic cancer is among the leading lethal malignancies in both sexes owing to its poor prognosis[<reflink idref="bib1" id="ref3">1</reflink>]. Approximately, 80% of pancreatic cancer diagnosis occurs in locally advanced (LA) or metastatic stages[<reflink idref="bib1" id="ref4">1</reflink>]. Gemcitabine-based chemotherapy remains the priority first-line intervention for the LA or metastatic pancreatic cancer (mPC) patient population[<reflink idref="bib2" id="ref5">2</reflink>],[<reflink idref="bib3" id="ref6">3</reflink>]. Nevertheless, mPC patient prognosis is extremely poor, with a median overall survival (mOS) of only 6–8 months, and 5-year OS of 7–9%[<reflink idref="bib1" id="ref7">1</reflink>]. About 25% of patients with LA pancreatic cancer at first visit experience an mOS of 6–9 months. Moreover, between 60 and 70% of patients with mPC have an mOS of 3–5 months[<reflink idref="bib4" id="ref8">4</reflink>]. Given these dire circumstances, it is both urgent and necessary to identify novel and efficacious treatment strategies or combined therapeutic strategies that enhance patient outcomes.</p> <p>The K-Ras oncogene is often mutated in cancer cells. In fact, 1 in 7 cancers harbor mutations in this gene. Moreover, its mutations and/or wild-type amplifications are common in pancreatic cancer[<reflink idref="bib5" id="ref9">5</reflink>]. Nimotuzumab is a humanized IgG1 monoclonal antibody that targets the EGFR extracellular domain to suppress the EGFR axis and depress tumor cell proliferation, survival, and angiogenesis. Thus, it has great potential as an efficacious drug advanced pancreatic cancer[<reflink idref="bib6" id="ref10">6</reflink>],[<reflink idref="bib7" id="ref11">7</reflink>]. A German phase II study (PCS07) reported that, among patients with LA or mPC, a nimotuzumab and gemcitabine combination, relative to placebo plus gemcitabine, significantly enhanced mOS (8.6 months vs. 6.0 months), particularly among patients with K-Ras wild type (11.6 months vs. 5.6 months), and the corresponding 1-year OS rates were 53.8% and 15.8%, respectively[<reflink idref="bib8" id="ref12">8</reflink>]. Subsequently, the Chinese Society of Clinical Oncology (CSCO) Recommendations for the Detection and Intervention of Pancreatic Cancer approved nimotuzumab plus gemcitabine as a first-line intervention for patients with K-Ras wild type LA or mPC.</p> <p>The NOTABLE trial was the first recorded phase III clinical investigation of the first-line intervention involving nimotuzumab plus gemcitabine for patients with K-Ras wild type LA or mPC in China[<reflink idref="bib9" id="ref13">9</reflink>]. Based on their findings, nimotuzumab plus gemcitabine strongly enhanced mOS (10.9 vs. 8.5 months, hazard ratio [HR] 0.50, 95% confidence interval [CI] 0.06–0.94, <emph>P</emph> = 0.024) as well as progression-free survival (PFS, 4.2 vs. 3.6 months, hazard ratio [HR] 0.56, 95% confidence interval [CI] 0.12–0.99, <emph>P</emph> = 0.013) of the aforementioned patient population. In terms of safety, they observed that the grade 3 treatment-associated adverse events (AEs) were comparable between both patient cohorts (26.7% vs. 24.4%), and there were no cases of grade 4 treatment-associated AEs.</p> <p>Although a combined nimotuzumab plus gemcitabine intervention demonstrated obvious clinical benefits, and is, therefore, an attractive therapeutic option, it is still unclear whether its cost is feasible for the general population in China. Thus far, there is no relative analysis of nimotuzumab plus gemcitabine treatment cost-efficiency anywhere in the world. Herein, our goal was the assess the expenditure efficacy of nimotuzumab plus gemcitabine versus gemcitabine alone as first-line therapy for patients with K-Ras wild type LA or mPC, based on the NOTABLE trial, and from the perspective of a Chinese patient.</p> <hd id="AN0183309807-3">Materials and methods</hd> <p>The present analysis was conducted as per the Consolidated Health Economic Evaluation Reporting Standards 2022 guideline for economic evaluations (Table S1).</p> <hd id="AN0183309807-4">Patient population and intervention</hd> <p>The clinical population, treatment programs, robustness, and safety information were all acquired from the randomized, double-blind, placebo-controlled, multicenter, phase 3 NOTABLE trial (ClinicialTrials.gov number, NCT02395016) conducted in China[<reflink idref="bib9" id="ref14">9</reflink>]. The following patients were included in analysis: aged between 18 and 75; histologically or cytologically confirmed LA or mPC diagnosis; K-Ras wild type status; Karnofsky performance score ≥ 60; and ≥ 1 measurable lesions per Response Evaluation Criteria in Solid Tumors version 1.1. Study participants were randomly placed in an nimotuzumab plus gemcitabine (n = 46) or gemcitabine alone (n = 46) cohort. Nimotuzumab (400 mg, weekly) and subsequent gemcitabine (1000 mg/m2 on days 1, 8, and 15, every four weeks), or placebo plus gemcitabine was provided until disease progression or intolerable toxic effect occurrence, at which point, patients were transferred to second-line intervention. Disease progression was evident in 33% and 27% of the aforementioned treated cohorts, respectively, and these patients were provided with the best supportive care. Terminal care was provided prior to treatment-related death. However, since the trial lacked specific subsequent therapeutic medications, we presumed nal-IRI + 5-FU/LV (nal-irinotecan; 5-fluorouracil, leucovorin) was provided as follow-up chemotherapy, based on the NCCN and CSCO recommendations for LA or mPC Grade I second-line intervention[<reflink idref="bib2" id="ref15">2</reflink>],[<reflink idref="bib3" id="ref16">3</reflink>],[<reflink idref="bib10" id="ref17">10</reflink>].</p> <hd id="AN0183309807-5">Model generation</hd> <p>To simulate disease progression following nimotuzumab plus gemcitabine first-line therapy among patients with K-Ras wild type LA or mPCin China, we integrated clinical and economic statuses to generate an exhaustive decision-analytical Markov model integrating 3 distinctive health conditions—PFS, progressive disease (PD), and mortality. In individual Markov cycle, all patients in PFS were initially treated with either nimotuzumab plus gemcitabine or gemcitabine alone, and were monitored to reveal whether they remain in their initial state or experienced progressed disease[<reflink idref="bib11" id="ref18">11</reflink>]. In case of disease progression or intolerable toxic reactions, both patient cohorts were administered comprehensive intervention until death (Figure S1).</p> <p>To adjust for differences in dosage frequencies as per the clinical trial drug administration, the model cycle was set to 3 months and run for 10 years considering that about 90% of patients in the cohort died, during which time most patients in both groups expired. Based on the recommendations from the Evaluation of Chinese Pharmacoeconomics (2019), all costs and outcomes were discounted annually at a rate of 5%[<reflink idref="bib12" id="ref19">12</reflink>]. The primary endpoints of the generated model were total expenditure, quality-adjusted life years (QALYs), and incremental cost‒effectiveness ratio (ICER) which demonstrated the incremental expenditure of individual QALY. The willingness-to-pay (WTP) threshold was based on the triple 2022 Chinese per capita gross domestic product (GDP) of $36,289/QALY, as reported by the World Health Organization. Moreover, although our model was primarily based on the NOTABLE trial, its structure and data were further supplemented by publicly available scientific resources. Lastly, model construction employed TreeAge Pro 2022 (TreeAge Software, Inc.).</p> <hd id="AN0183309807-6">Model survival and transition likelihoods</hd> <p>Using short-term OS and PFS information from Kaplan–Meier survival curves in the NOTABLE trial, we next predicted transition likelihoods between distinct health conditions. Owing to unavailability of individual patient information, we utilized the Get Data Graph Digitizer 2.26 tool to extract information from both cohorts, using a protocol reported by Rini et al.[<reflink idref="bib13" id="ref20">13</reflink>]. The subsequent information was then employed toward fitting a parametric survival model. In selecting the survival model, although the lognormal and loglogistic distributions yielded the lowest Akaike information criterion (AIC) and Bayesian information criterion (BIC) values, they did not account for the applicability of the follow-up period in the final model assessment. Additionally, their weighted tails could lead to an overestimation of long-term OS and PFS. After a comprehensive evaluation of AIC, BIC as well as visual inspection, the Weibull distribution was found to be the most suitable fit for the pseudo-individual patient information compared with the exponential, loglogistic, log-normal, and Gompertz distributions[<reflink idref="bib14" id="ref21">14</reflink>]. Owing to its accommodating and widespread usage in assessing cancer OS, the Weibull distribution was determined to align patient quantity among the 3 health states over time[<reflink idref="bib15" id="ref22">15</reflink>],[<reflink idref="bib16" id="ref23">16</reflink>]. Table S2 and Figure S2 provide a comprehensive overview of the survival model selection procedure. Specific survival model parameters are listed in Table 1.</p> <p>Table 1 Key parameters.</p> <p> <ephtml> <table frame="hsides" rules="groups"><thead><tr><th align="left"><p>Variable</p></th><th align="left"><p>Mean value (range)</p></th><th align="left"><p>Reference</p></th><th align="left"><p>Distribution</p></th></tr></thead><tbody><tr><td align="left" colspan="4"><p>Clinical parameters</p></td></tr><tr><td align="left" colspan="4"><p> Weibull survival model for nimotuzumab plus chemotherapy</p></td></tr><tr><td align="left"><p> OS</p></td><td align="left"><p>Scale = 0.10701, Shape = 0.80324</p></td><td align="left"><p>–</p></td><td align="left"><p>–</p></td></tr><tr><td align="left"><p> PFS</p></td><td align="left"><p>Scale = 0.08603, Shape = 0.83713</p></td><td align="left"><p>–</p></td><td align="left"><p>–</p></td></tr><tr><td align="left" colspan="4"><p> Weibull survival model for chemotherapy</p></td></tr><tr><td align="left"><p> OS</p></td><td align="left"><p>Scale = 0.07444, Shape = 1.09557</p></td><td align="left"><p>–</p></td><td align="left"><p>–</p></td></tr><tr><td align="left"><p> PFS</p></td><td align="left"><p>Scale = 0.06402, Shape = 1.12822</p></td><td align="left"><p>–</p></td><td align="left"><p>–</p></td></tr><tr><td align="left" colspan="4"><p> Rate of post-discontinuation therapy</p></td></tr><tr><td align="left"><p> Nimotuzumab plus chemotherapy group</p></td><td align="left"><p>0.330 (0.264–0.396)</p></td><td align="left"><p><xref ref-type="bibr" rid="bibr9">9</xref></p></td><td align="left"><p>Beta</p></td></tr><tr><td align="left"><p> Chemotherapy group</p></td><td align="left"><p>0.270 (0.216–0.324)</p></td><td align="left"><p><xref ref-type="bibr" rid="bibr9">9</xref></p></td><td align="left"><p>Beta</p></td></tr><tr><td align="left" colspan="4"><p> Risk for main AEs in nimotuzumab plus chemotherapy group</p></td></tr><tr><td align="left"><p> White blood cell count decreased</p></td><td align="left"><p>0.089 (0.071–0.107)</p></td><td align="left"><p><xref ref-type="bibr" rid="bibr9">9</xref></p></td><td align="left"><p>Beta</p></td></tr><tr><td align="left"><p> Neutrophil count decreased</p></td><td align="left"><p>0.111 (0.089–0.133)</p></td><td align="left"><p><xref ref-type="bibr" rid="bibr9">9</xref></p></td><td align="left"><p>Beta</p></td></tr><tr><td align="left"><p> Platelet count decreased</p></td><td align="left"><p>0.067 (0.054–0.080)</p></td><td align="left"><p><xref ref-type="bibr" rid="bibr9">9</xref></p></td><td align="left"><p>Beta</p></td></tr><tr><td align="left" colspan="4"><p> Risk for main AEs in chemotherapy group</p></td></tr><tr><td align="left"><p> White blood cell count decreased</p></td><td align="left"><p>0.067 (0.054–0.080)</p></td><td align="left"><p><xref ref-type="bibr" rid="bibr9">9</xref></p></td><td align="left"><p>Beta</p></td></tr><tr><td align="left"><p> Neutrophil count decreased</p></td><td align="left"><p>0.089 (0.071–0.107)</p></td><td align="left"><p><xref ref-type="bibr" rid="bibr9">9</xref></p></td><td align="left"><p>Beta</p></td></tr><tr><td align="left"><p> Platelet count decreased</p></td><td align="left"><p>0.089 (0.071–0.107)</p></td><td align="left"><p><xref ref-type="bibr" rid="bibr9">9</xref></p></td><td align="left"><p>Beta</p></td></tr><tr><td align="left" colspan="4"><p> Utility and disutility</p></td></tr><tr><td align="left"><p> Utility of PFS</p></td><td align="left"><p>0.850 (0.680–1.020)</p></td><td align="left"><p><xref ref-type="bibr" rid="bibr17">17</xref>,<xref ref-type="bibr" rid="bibr18">18</xref></p></td><td align="left"><p>Beta</p></td></tr><tr><td align="left"><p> Utility of PD</p></td><td align="left"><p>0.730 (0.584–0.876)</p></td><td align="left"><p><xref ref-type="bibr" rid="bibr17">17</xref>,<xref ref-type="bibr" rid="bibr18">18</xref></p></td><td align="left"><p>Beta</p></td></tr><tr><td align="left"><p> Disutility of WBC count decreased</p></td><td align="left"><p>0.090 (0.072–0.108)</p></td><td align="left"><p><xref ref-type="bibr" rid="bibr19">19</xref></p></td><td align="left"><p>Beta</p></td></tr><tr><td align="left"><p> Disutility of Neutrophil count decreased</p></td><td align="left"><p>0.090 (0.072–0.108)</p></td><td align="left"><p><xref ref-type="bibr" rid="bibr19">19</xref></p></td><td align="left"><p>Beta</p></td></tr><tr><td align="left"><p> Disutility of Platelet count decreased</p></td><td align="left"><p>0.650 (0.520–0.780)</p></td><td align="left"><p><xref ref-type="bibr" rid="bibr19">19</xref></p></td><td align="left"><p>Beta</p></td></tr><tr><td align="left" colspan="4"><p>Cost, $/per cycle</p></td></tr><tr><td align="left" colspan="4"><p> Treatment cost</p></td></tr><tr><td align="left"><p> Nimotuzumab 1st cycle</p></td><td align="left"><p>11,343 (9074–13,612)</p></td><td align="left"><p>Real World</p></td><td align="left"><p>Gamma</p></td></tr><tr><td align="left"><p> Nimotuzumab subsequent cycle</p></td><td align="left"><p>9722 (7778–116,668)</p></td><td align="left"><p>Real World</p></td><td align="left"><p>Gamma</p></td></tr><tr><td align="left"><p> Gemcitabine</p></td><td align="left"><p>87 (70–104)</p></td><td align="left"><p>Real World</p></td><td align="left"><p>Gamma</p></td></tr><tr><td align="left"><p> Nal-irinotecan</p></td><td align="left"><p>26,948 (21,558–32,338)</p></td><td align="left"><p>Real World</p></td><td align="left"><p>Gamma</p></td></tr><tr><td align="left"><p> LV</p></td><td align="left"><p>146 (117–175)</p></td><td align="left"><p>Real World</p></td><td align="left"><p>Gamma</p></td></tr><tr><td align="left"><p> 5-FU</p></td><td align="left"><p>450 (360–540)</p></td><td align="left"><p>Real World</p></td><td align="left"><p>Gamma</p></td></tr><tr><td align="left" colspan="4"><p> Cost of AEs</p></td></tr><tr><td align="left"><p> Nimotuzumab plus chemotherapy group</p></td><td align="left"><p>332 (265.6–398)</p></td><td align="left"><p><xref ref-type="bibr" rid="bibr20">20</xref></p></td><td align="left"><p>Gamma</p></td></tr><tr><td align="left"><p> Chemotherapy group</p></td><td align="left"><p>391 (312.8–469.2)</p></td><td align="left"><p><xref ref-type="bibr" rid="bibr20">20</xref></p></td><td align="left"><p>Gamma</p></td></tr><tr><td align="left"><p>Laboratory</p></td><td align="left"><p>116 (92.8–139.2)</p></td><td align="left"><p><xref ref-type="bibr" rid="bibr21">21</xref></p></td><td align="left"><p>Gamma</p></td></tr><tr><td align="left"><p>Tumor imaging</p></td><td align="left"><p>378 (302.4–453.6)</p></td><td align="left"><p><xref ref-type="bibr" rid="bibr21">21</xref></p></td><td align="left"><p>Gamma</p></td></tr><tr><td align="left"><p>Adminstration</p></td><td align="left"><p>369 (295.2–442.8)</p></td><td align="left"><p><xref ref-type="bibr" rid="bibr18">18</xref></p></td><td align="left"><p>Gamma</p></td></tr><tr><td align="left"><p>Best supportive care</p></td><td align="left"><p>468 (374.4–561.6)</p></td><td align="left"><p><xref ref-type="bibr" rid="bibr22">22</xref></p></td><td align="left"><p>Gamma</p></td></tr><tr><td align="left"><p>Terminal care per patient</p></td><td align="left"><p>7794 (6235.2–9352.8)</p></td><td align="left"><p><xref ref-type="bibr" rid="bibr22">22</xref></p></td><td align="left"><p>Gamma</p></td></tr><tr><td align="left"><p>Discount rate</p></td><td align="left"><p>0.05 (0–0.08)</p></td><td align="left"><p><xref ref-type="bibr" rid="bibr12">12</xref></p></td><td align="left"><p>Uniform</p></td></tr></tbody></table> </ephtml> </p> <p>OS, overall survival; PFS, progression-free survival; PD, disease progressed; WBC, White blood cell; LV, leucovorin; 5-FU, 5-Fluoropyrimidine; AEs, adverse events; NC, nimotuzumab plus chemotherapy.</p> <hd id="AN0183309807-7">Utility and expenditure input</hd> <p>We predicted total QALYs via health-associated quality of life (QoL)-mediated adjustment of OS duration. Utility was used to assess patient health-associated QoL at a particular health condition. We avoided disclosing QoL data from the NOTABLE trial, and derived 0.85 and 0.73 average health utility values for the PFS and PD states, respectively, from prior publications[<reflink idref="bib17" id="ref24">17</reflink>],[<reflink idref="bib18" id="ref25">18</reflink>]. In addition, the mean utility was normalized based on the grade 3/4 AEs disutility values[<reflink idref="bib19" id="ref26">19</reflink>]. Direct medical expenditure constituted the following: drug costs, treatment-related AEs management (given that AEs occurred only once during the PFS and PD conditions), laboratory examinations, routine tumor imaging, administration, BSC, and terminal care (Table 1). Intervention expenditure was acquired from relevant and local hospital sources. Nimotuzumab price was sourced from Tai Xin Sheng®, Baitai Biological Pharmaceutical Co., Ltd., China, as nal-irinotecan was not yet available in mainland China, and the drug price referred to Hong Kong prices. Other direct medical expenses were based on published reports[<reflink idref="bib18" id="ref27">18</reflink>],[<reflink idref="bib20" id="ref28">20</reflink>], [<reflink idref="bib21" id="ref29">21</reflink>]–[<reflink idref="bib22" id="ref30">22</reflink>]. Specific treatment drugs and unit costs were shown in Table S3. To compute chemotherapeutic agent dosage, we assumed that an average patient was of 65 kg weight and 1.64 m height, giving him a body surface area (BSA) of 1.72 m<sups>2</sups>[<reflink idref="bib23" id="ref31">23</reflink>]. Since the Chinese government controls healthcare costs to maintain stability, there was no need of an inflation adjustment in the present analysis. Prices are presented in US dollars, with a conversion rate of $1 = ￥7.0848 (June 2023).</p> <hd id="AN0183309807-8">Sensitivity analyses</hd> <p>To assess the decision-analytical model performance, and to elucidate the uncertainty influence that individual variables have on the overall model results, furthermore, we conducted the impact of diverse variables and performed several sensitivity analyses. One-way sensitivity analyses were performed to examine the personal separate effects of parameter via variation of all parameters by ± 20% of baseline. This was based on the recognized technique for uncertainty impacts assessment on ICERs[<reflink idref="bib24" id="ref32">24</reflink>]. We also examined the likelihood of nimotuzumab plus gemcitabine cost-efficiency by performing likelihood sensitivity analyses with 10,000 Monte Carlo repetitions[<reflink idref="bib24" id="ref33">24</reflink>]. Acceptability curves, scatter plots, and tornado diagrams were next constructed to display the results of aforementioned sensitivity analyses. Lastly, subgroup analyses were performed on patients employed in the NOTABLE trial forest plot, according to the subgroup-specified HRs using the Hoyle et al.[<reflink idref="bib25" id="ref34">25</reflink>] approach.</p> <hd id="AN0183309807-9">Results</hd> <p></p> <hd id="AN0183309807-10">Base-case analysis</hd> <p>Among all patients, the curative efficiency (total costs) were 2.94 QALYs ($161,774) among patients with nimotuzumab plus gemcitabine and 1.83 QALYs ($38,330) among patients with gemcitabine alone (ICER value, $111,556/QALY; INHB value, − 2.29/QALY). Relative to gemcitabine alone, patients with K-Ras wild type LA or mPC who received nimotuzumab plus gemcitabine as first-line treatment provided an additional 1.11 QALYs (1.25 LYs) at an incremental cost of $123,444 within a 10-year horizon, which contributed to an ICER value of $111,556 per QALY ($98,929 per LY) at a WTP threshold of $36,289/QALY within China (Table 2). When the cost of nimotuzumab is reduced by 90%, the ICERs were $34,811/QALY, making nimotuzumab and gemcitabine combination a cost-effective treatment option (Table S4).</p> <p>Table 2 Results of the base-case analysis.</p> <p> <ephtml> <table frame="hsides" rules="groups"><thead><tr><th align="left" rowspan="2"><p>Treatment</p></th><th align="left" rowspan="2"><p>Total cost, $</p></th><th align="left" rowspan="2"><p>Overall LYs</p></th><th align="left" rowspan="2"><p>Overall QALYs</p></th><th align="left" colspan="2"><p>ICER, $</p></th><th align="left" rowspan="2"><p>INHB, QALY</p></th></tr><tr><th align="left"><p>Per LY</p></th><th align="left"><p>Per QALY</p></th></tr></thead><tbody><tr><td align="left"><p>Chemotherapy</p></td><td char="," align="char"><p>38,330</p></td><td char="." align="char"><p>2.10</p></td><td char="." align="char"><p>1.83</p></td><td align="left"><p>Reference</p></td><td align="left"><p>Reference</p></td><td align="left"><p>Reference</p></td></tr><tr><td align="left"><p>Nimotuzumab plus chemotherapy</p></td><td char="," align="char"><p>161,774</p></td><td char="." align="char"><p>3.35</p></td><td char="." align="char"><p>2.94</p></td><td align="left"><p>98,929</p></td><td align="left"><p>111,556</p></td><td align="left"><p>− 2.29</p></td></tr></tbody></table> </ephtml> </p> <p>LYs, life-years; QALYs, quality-adjusted life-years; ICER, incremental cost-effectiveness ratio; INHB, incremental net health benefits.</p> <hd id="AN0183309807-11">Sensitivity analysis</hd> <p>The results of our one-way sensitivity analysis are presented in tornado diagrams (Fig. 1). We demonstrated that the PFS utility was the most sensitive parameter, exerting a considerable impact on our model-based conclusions, with variations from 1.02 to 0.68 coinciding with ICERs ranging from $97,785/QALY to $ 129,842/QALY. Other considerable influential parameters were the nimotuzumab cost, PD utility, and nal-irinotecan cost. ICERs were consistently above the WTP cut-off of $36,289/QALY no matter the changes in parameter values. The cost-efficiency acceptability curve (Fig. 2) and ICER scatter plots (Figure S3) produced in the likelihood sensitivity analysis further confirmed that nimotuzumab plus gemcitabine usage has 0% possibility of being cost-efficient, relative to gemcitabine alone, at a WTP cut-off of $36,289. The ICER consistently exceeded the WTP cut-off, and negative INHBs were observed across all patient subcategories with zero possibility of being cost-efficient in any of the subgroup analyses (Table 3).</p> <p>Graph: Fig. 1 The one-way sensitivity analyses for nimotuzumab plus gemcitabine strategy compared to gemcitabine strategy. PFS, progression-free survival; PD, progressive disease; NC, nimotuzumab plus chemotherapy(gemcitabine); C, chemotherapy(gemcitabine); WTP, willingness-to-pay; ICER, incremental cost-effectiveness ratio; QALY, quality-adjusted life-year.</p> <p>Graph: Fig. 2 The cost-effectiveness acceptability curves for nimotuzumab plus chemotherapy(gemcitabine) strategy compared to chemotherapy(gemcitabine) strategy in the overall patients. WTP, willingness-to-pay; QALY, quality-adjusted life-year.</p> <p>Table 3 Results of subgroup analyses.</p> <p> <ephtml> <table frame="hsides" rules="groups"><thead><tr><th align="left" rowspan="2"><p>Subgroup</p></th><th align="left" rowspan="2"><p>OS HR (95% CI)</p></th><th align="left" rowspan="2"><p>PFS HR (95% CI)</p></th><th align="left" rowspan="2"><p>ICER, $/QALY</p></th><th align="left" rowspan="2"><p>INHB, QALYs</p></th><th align="left"><p>Cost-effectiveness probability of nimotuzumab plus chemotherapy at WTP, %</p></th></tr><tr><th align="left"><p>$36,289/QALY</p></th></tr></thead><tbody><tr><td align="left" colspan="6"><p>Tumor site</p></td></tr><tr><td align="left"><p> Head</p></td><td align="left"><p>0.75 (0.37–1.51)</p></td><td align="left"><p>0.52 (0.23–1.16)</p></td><td align="left"><p>193,663</p></td><td align="left"><p>− 1.99</p></td><td align="left"><p>0%</p></td></tr><tr><td align="left"><p> Body or tail</p></td><td align="left"><p>0.59 (0.32–1.11)</p></td><td align="left"><p>0.82 (0.38–1.15)</p></td><td align="left"><p>130,289</p></td><td align="left"><p>− 2.17</p></td><td align="left"><p>0%</p></td></tr><tr><td align="left" colspan="6"><p>Previous surgery</p></td></tr><tr><td align="left"><p> Yes</p></td><td align="left"><p>0.98 (0.54–1.79)</p></td><td align="left"><p>0.81 (0.41–1.59)</p></td><td align="left"><p>102,7289</p></td><td align="left"><p>− 1.79</p></td><td align="left"><p>0%</p></td></tr><tr><td align="left"><p> No</p></td><td align="left"><p>0.40 (0.19–0.84)</p></td><td align="left"><p>0.44 (0.21–0.94)</p></td><td align="left"><p>97,094</p></td><td align="left"><p>− 2.42</p></td><td align="left"><p>0%</p></td></tr><tr><td align="left" colspan="6"><p>Previous treatment of biliary obstrucion</p></td></tr><tr><td align="left"><p> Yes</p></td><td align="left"><p>NA</p></td><td align="left"><p>NA</p></td><td align="left"><p>NA</p></td><td align="left"><p>NA</p></td><td align="left"><p>NA</p></td></tr><tr><td align="left"><p> No</p></td><td align="left"><p>0.54 (0.33–0.88)</p></td><td align="left"><p>0.50 (0.29–0.86)</p></td><td align="left"><p>118,779</p></td><td align="left"><p>− 2.26</p></td><td align="left"><p>0%</p></td></tr><tr><td align="left" colspan="6"><p>Previous adjuvant chemotherapy</p></td></tr><tr><td align="left"><p> Yes</p></td><td align="left"><p>0.39 (0.03–4.44)</p></td><td align="left"><p>NA</p></td><td align="left"><p>NA</p></td><td align="left"><p>NA</p></td><td align="left"><p>NA</p></td></tr><tr><td align="left"><p> No</p></td><td align="left"><p>0.68 (0.43–1.09)</p></td><td align="left"><p>0.62 (0.37–1.03)</p></td><td align="left"><p>157,583</p></td><td align="left"><p>− 2.09</p></td><td align="left"><p>0%</p></td></tr><tr><td align="left" colspan="6"><p>Disease type</p></td></tr><tr><td align="left"><p> Local advanced</p></td><td align="left"><p>0.74 (0.27–2.07)</p></td><td align="left"><p>0.37 (0.09–1.49)</p></td><td align="left"><p>185,794</p></td><td align="left"><p>− 2.02</p></td><td align="left"><p>0%</p></td></tr><tr><td align="left"><p> Metastatic</p></td><td align="left"><p>0.64 (0.38–1.08)</p></td><td align="left"><p>0.66 (0.38–1.13)</p></td><td align="left"><p>143,577</p></td><td align="left"><p>− 2.14</p></td><td align="left"><p>0%</p></td></tr><tr><td align="left" colspan="6"><p>KPS score</p></td></tr><tr><td align="left"><p> 60–80</p></td><td align="left"><p>0.53 (0.27–1.05)</p></td><td align="left"><p>0.48 (0.23–0.99)</p></td><td align="left"><p>117,260</p></td><td align="left"><p>− 2.23</p></td><td align="left"><p>0%</p></td></tr><tr><td align="left"><p> 80–100</p></td><td align="left"><p>0.81 (0.43–1.56)</p></td><td align="left"><p>0.81 (0.41–1.61)</p></td><td align="left"><p>241,568</p></td><td align="left"><p>− 1.94</p></td><td align="left"><p>0%</p></td></tr><tr><td align="left" colspan="6"><p>Gender</p></td></tr><tr><td align="left"><p> Male</p></td><td align="left"><p>0.64 (0.36–1.15)</p></td><td align="left"><p>0.58 (0.31–1.07)</p></td><td align="left"><p>146,099</p></td><td align="left"><p>− 2.08</p></td><td align="left"><p>0%</p></td></tr><tr><td align="left"><p> Female</p></td><td align="left"><p>0.62 (0.28–1.36)</p></td><td align="left"><p>0.47 (0.19–1.20)</p></td><td align="left"><p>138,171</p></td><td align="left"><p>− 2.14</p></td><td align="left"><p>0%</p></td></tr><tr><td align="left" colspan="6"><p>Age</p></td></tr><tr><td align="left"><p> < 65 years</p></td><td align="left"><p>0.70 (0.41–1.19)</p></td><td align="left"><p>0.61 (0.35–1.07)</p></td><td align="left"><p>168,445</p></td><td align="left"><p>− 2.02</p></td><td align="left"><p>0%</p></td></tr><tr><td align="left"><p> ≥ 65 years</p></td><td align="left"><p>0.54 (0.19–1.52)</p></td><td align="left"><p>0.52 (0.18–1.53)</p></td><td align="left"><p>119,174</p></td><td align="left"><p>− 2.23</p></td><td align="left"><p>0%</p></td></tr><tr><td align="left" colspan="6"><p>Course of disease</p></td></tr><tr><td align="left"><p> < 1 year</p></td><td align="left"><p>0.60(0.36–0.99)</p></td><td align="left"><p>0.60(0.35–1.03)</p></td><td align="left"><p>132,875</p></td><td align="left"><p>− 2.16</p></td><td align="left"><p>0%</p></td></tr><tr><td align="left"><p> ≥ 1 year</p></td><td align="left"><p>1.42(0.33–6.08)</p></td><td align="left"><p>0.48(0.10–2.15)</p></td><td align="left"><p>− 106,491</p></td><td align="left"><p>− 1.57</p></td><td align="left"><p>0%</p></td></tr></tbody></table> </ephtml> </p> <p>NA, The sample size was unavailable or too small and was not further calculated. CI, confidence interval; OS HR, overall survival hazard ratio; PFS HR, progression-free survival hazard ratio; ICER, incremental cost-effectiveness ratio; INHB, incremental net health benefits; QALY, quality-adjusted life-year; WTP, Willingness-to-pay; KPS, Karnofsky performance status;</p> <hd id="AN0183309807-12">Discussion</hd> <p>Owing to an mOS of only 6–8 months, pancreatic cancer is among the most lethal malignancies that are diagnosed at LA or mPC, at which point treatment options are gravely ineffective[<reflink idref="bib1" id="ref35">1</reflink>]. More recently, new active treatments have shown significant clinical benefits in patients with LA and mPC. Moreover, one phase II investigation demonstrated that a combined nimotuzumab plus gemcitabine treatment can great enhance clinical activity[<reflink idref="bib8" id="ref36">8</reflink>]. Till date, the NOTABLE study is the only phase III investigation that reported a double benefit of targeted nimotuzumab plus gemcitabine therapy in treating patients with K-Ras wild type LA or mPC. Thus, nimotuzumab has become a promising new drug for the first-line intervention of this patient population. Unfortunately, the exceedingly high drug prices can often place heavy economic burdens on the patients, as well as the national medical and health system. Thus, to maximize use of limited resources, it is essential to conduct an economic evaluation and re-examination of new treatments and expensive drugs to elucidate the balance between benefits and costs for patients and the entire health system, such that the health care system continues to provide equal and accessible medical services and assist patients to benefit from advanced medical progress.</p> <p>Different economic conditions in various countries may contribute to distinct cost-efficiency outcomes. In a study by Morimoto et al.[<reflink idref="bib26" id="ref37">26</reflink>], a combination therapy involving nab-paclitaxel plus gemcitabine as first-line intervention for unresectable mPC was proven to be quite costly, relative to gemcitabine therapy alone, in Japan. In a separate investigation by Cui et al.[<reflink idref="bib27" id="ref38">27</reflink>], examining the retrospective real-world investigation by Kang et al.[<reflink idref="bib28" id="ref39">28</reflink>] in China revealed that the combinational intervention of nab-paclitaxel plus gemcitabine was, in fact, a cost-effective first-line intervention for mPC, relative to FOLFIRINOX. Additionally, Bao et al.[<reflink idref="bib29" id="ref40">29</reflink>] reported that a combination therapy with erlotinib plus gemcitabine as first-line intervention for mPC was not economically beneficial, based on the Markov model. However, it is important to note that this study solely relied on the PA.3 trial[<reflink idref="bib30" id="ref41">30</reflink>], and therefore, may not completely represent the clinical application and health condition of the general Chinese population. Based on our current understanding, we are the first to report a cost-effective analysis of nimotuzumab plus gemcitabine versus gemcitabine alone as the first-line intervention for Chinese patients with K-Ras wild type LA or mPC, based on the current clinical recommendations. Our analyses and conclusions will have great significance for policymakers and payment negotiators and will provide valuable insight into formulating future treatment strategies.</p> <p>Herein, we revealed that, relative to gemcitabine alone, nimotuzumab plus gemcitabine made an additional 1.11 QALYs (1.25 LYs), at an incremental cost of $123,444, within a 10-year horizon, thus producing an ICER value of $111,556 per QALY ($98,929 per LY) at a WTP cut-off of $36,289/QALY in China, which was greater than $36,289/QALY. Thus, a combined nimotuzumab plus gemcitabine therapy was not considered cost-effective in this study. Regardless of the variations within specific ranges for the most sensitive variables, it is highly improbable that a nimotuzumab plus gemcitabine intervention would be considered cost-efficient in China, based on our likelihood sensitivity analysis results. Based on our one-way sensitivity analysis, PFS utility contributed the most to ICER regulation. Additionally, our acceptability curve suggested that the ICER was influenced by WTP value alterations, which, in turn, was affected by the Chinese GDP per capita. Herein, we utilized 3 times GDP per capita as the criteria for WTP cut-off definition[<reflink idref="bib31" id="ref42">31</reflink>]. Despite the potential lack of nimotuzumab cost-effectiveness in China, considering the large survival benefits, lower drug price would be beneficial in ensuring patients receive best possible care. Our sensitivity analysis further indicated that, with reduced price, the economic outcomes potentially become more favorable. Our scenario analysis founds that when the cost of nimotuzumab is reduced by 90%, nimotuzumab plus gemcitabine combination therapy will be considered a cost-effective treatment option. Hence, it is critical to consider the evolving cost dynamics and potential improvements in drug cost-effectiveness with a reduced nimotuzumab price. Engaging in negotiations that balance drug pricing and coverage scope can potentially lower its cost while enhancing cost-effectiveness. However, achieving a 90% reduction in drug prices is extremely difficult. Indiscriminately lowering drug prices reveals the impractical cost-effectiveness of nimotuzumab plus gemcitabine combination therapy, highlighting its limited accessibility in clinical practice. Cost-effectiveness is also modulated by various factors within a specified subgroup. Proper identification and analysis of these factors can enrich policymakers and researchers with the appropriate insight into which subgroups will likely benefit from cost-effective interventions. Accordingly, cost-effectiveness-related characteristics, such as, tumor site, prior surgery, prior biliary obstruction intervention, and prior adjuvant gemcitabine factors must be taken into consideration. However, it should be noted that a nimotuzumab plus gemcitabine combined therapy is not universally cost-effective across all patient subpopulations.</p> <p>This study has some notable strengths. Firstly, this is the first performed cost-efficient analysis in China and the world that combined nimotuzumab plus gemcitabine therapy as a first-line intervention for patients with K-Ras wild type LA or mPC, in combination with the latest evidence. Secondly, all NOTABLE trial participants were of Chinese origin, which facilitated the direct comparison of nimotuzumab plus gemcitabine treatment efficacy and safety within the context of the Chinese healthcare system. As a result, our conclusions are readily applicable to the general Chinese population. In addition, our conclusions will be highly beneficial to clinicians, government, and healthcare financial institutions, and will assist them in making well-informed and effective decisions. Finally, our findings will provide supportive information for the multilateral nimotuzumab price negotiators in both domestic and international markets.</p> <p>Certain limitations of our study deserve consideration. First, we utilized a Markov model to compare between traditional gemcitabine alone and nimotuzumab plus gemcitabine combination therapy. However, owing to missing long-term follow-up information, the efficacy may have been underestimated. Therefore, we employed a more parametric Weibull distribution model to extrapolate survival tails beyond our examined follow-up time frame, aiming to capture the full survival benefits. However, with the extension of follow-up duration, the OS data may evolve, and may not fully reflect real-world scenarios[<reflink idref="bib32" id="ref43">32</reflink>]. Second, while the treatment strategy cost was primarily obtained from real-world data, the remaining costs were acquired from selected published references. We failed to take into account indirect costs that could potentially influence the accuracy of our cost reduction. It was worth mentioning that since nal-irinotecan was not yet available in mainland China, the drug price referred to the price in Hong Kong, China, which may overestimate the actual cost of nal-irinotecan. Nevertheless, our one-way sensitivity analysis revealed that these costs posed negligible influence on the model conclusions, apart from the cost of nimotuzumab, and the ICER value was always higher than the WTP threshold ($36,289/QALY) regardless of how these parameters were changed. Third, the selected utility values are critical for conducting pharmacoeconomic analyses, and, owing to the unavailability of complete Qol statistics in the NOTABLE trial, the health state utilities employed in our model were sourced from published literatures that primarily describe advanced and mPC. Single sensitivity variables representing utility parameters often influence model stability, though the negative effects of AEs come from the same literature, which may, in turn, inevitably introduce overestimated or underestimated utility value. Finally, we should note that, owing to the limited detailed information of individual subgroup, we were unable to comprehensively implement the model for each subgroup. Thus, caution is warranted while interpreting the results of the economic estimates from the aforementioned subgroup analyses.</p> <hd id="AN0183309807-13">Conclusion</hd> <p>The nimotuzumab plus gemcitabine combination therapy, relative to gemcitabine alone, is a cost-ineffective first-line intervention for patients with K-Ras wild type LA or mPC from the perspective of an average Chinese patient utilizing the current drug prices.</p> <hd id="AN0183309807-14">Acknowledgements</hd> <p>All authors had full access to all of the data in this study and took complete responsibility for the integrity of the data and accuracy of the data analysis.</p> <hd id="AN0183309807-15">Author contributions</hd> <p>R.L., H.G., and K.C. designed the experiment. R.L., H.G., and K.C. performed the experiments. R.L. analyzed the data. H.G. and K.C. contributed analysis tools and funding. R.L., H.G., and K.C. wrote the manuscript. All authors have reviewed and approved the manuscript.</p> <hd id="AN0183309807-16">Funding</hd> <p>This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.</p> <hd id="AN0183309807-17">Data availability</hd> <p>All authors had full access to all of the data in this study and took complete responsibility for the integrity of the data and accuracy of the data analysis. The datasets generated and/or analyzed during the current study are available from the corresponding author upon reasonable request.</p> <hd id="AN0183309807-18">Declarations</hd> <p></p> <hd id="AN0183309807-19">Competing interests</hd> <p>The authors declare no competing interests.</p> <hd id="AN0183309807-20">Ethical approval</hd> <p>This article is based on previously conducted studies and does not contain any new studies with human participants or animals performed by any of the authors, it does not require the approval of the independent ethics committee.</p> <hd id="AN0183309807-21">Supplementary Information</hd> <p>Graph: Supplementary Information.</p> <hd id="AN0183309807-22">Supplementary Information</hd> <p>The online version contains supplementary material available at https://doi.org/10.1038/s41598-025-90960-x.</p> <hd id="AN0183309807-23">Publisher's note</hd> <p>Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.</p> <ref id="AN0183309807-24"> <title> References </title> <blist> <bibl id="bib1" idref="ref3" type="bt">1</bibl> <bibtext> Sung H, Ferlay J, Siegel RL. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin. 2021; 71; 3: 209-249. 10.3322/caac.21660. 33538338</bibtext> </blist> <blist> <bibl id="bib2" idref="ref5" type="bt">2</bibl> <bibtext> (CSCO 2023). Chinese society of clinical oncology, pancreatic cancer. Available at: <ulink href="http://www.csco.org.cn/cn/index.aspx">http://www.csco.org.cn/cn/index.aspx</ulink>. Accessed 11 June 2023.</bibtext> </blist> <blist> <bibl id="bib3" idref="ref6" type="bt">3</bibl> <bibtext> NCCN (2023). NCCN Clinical Practice Guidelines in Oncology, pancreatic adenocarcinoma. Available at: https://<ulink href="http://www.nccn.org/guidelines/category%5f1">www.nccn.org/guidelines/category%5f1</ulink>. Accessed 11 June 2023.</bibtext> </blist> <blist> <bibl id="bib4" idref="ref8" type="bt">4</bibl> <bibtext> International agency for Research on Cancer. Available at: https://gco.iarc.fr/today/data/factsheets/populations/160-china-fact-sheets. Accessed 11 June 2023.</bibtext> </blist> <blist> <bibl id="bib5" idref="ref9" type="bt">5</bibl> <bibtext> Hofmann MH, Gerlach D, Misale S, Petronczki M, Kraut N. Expanding the reach of precision oncology by drugging all KRAS mutants. Cancer Discov. 2022; 12; 4: 924-937. 1:CAS:528:DC%2BB38Xht1Git73I. 10.1158/2159-8290.CD-21-1331. 35046095. 9394389</bibtext> </blist> <blist> <bibl id="bib6" idref="ref10" type="bt">6</bibl> <bibtext> Mazorra Z, Chao L, Lavastida A. Nimotuzumab: beyond the EGFR signaling cascade inhibition. Semin. Oncol. 2018; 45; 1–2: 18-26. 1:CAS:528:DC%2BC1cXhtVyqsb3N. 10.1053/j.seminoncol.2018.04.008. 30318080</bibtext> </blist> <blist> <bibl id="bib7" idref="ref11" type="bt">7</bibl> <bibtext> Talavera A, Friemann R, Gómez-Puerta S. Nimotuzumab, an antitumor antibody that targets the epidermal growth factor receptor, blocks ligand binding while permitting the active receptor conformation. Cancer Res. 2009; 69; 14: 5851-5859. 1:CAS:528:DC%2BD1MXosV2msbo%3D. 10.1158/0008-5472.CAN-08-4518. 19584289</bibtext> </blist> <blist> <bibl id="bib8" idref="ref12" type="bt">8</bibl> <bibtext> Schultheis B, Reuter D, Ebert MP. Gemcitabine combined with the monoclonal antibody nimotuzumab is an active first-line regimen in KRAS wildtype patients with locally advanced or metastatic pancreatic cancer: A multicenter, randomized phase IIb study. Ann. Oncol. Off. J. Eur. Soc. Med. Oncol. 2017; 28; 10: 2429-2435. 1:STN:280:DC%2BC1M%2Fjs12jtw%3D%3D. 10.1093/annonc/mdx343</bibtext> </blist> <blist> <bibl id="bib9" idref="ref13" type="bt">9</bibl> <bibtext> Qin S, Li J, Bai Y. Nimotuzumab plus gemcitabine for K-ras wild-type locally advanced or metastatic pancreatic cancer. J. Clin. Oncol. 2023; 41; 33: 5163-5173. 1:CAS:528:DC%2BB3sXisVChu7nO. 10.1200/JCO.22.02630. 37647576. 10666986. 1537.35249</bibtext> </blist> <blist> <bibtext> Wang-Gillam A, Li CP, Bodoky G. Nanoliposomal irinotecan with fluorouracil and folinic acid in metastatic pancreatic cancer after previous gemcitabine-based therapy (NAPOLI-1): A global, randomised, open-label, phase 3 trial. Lancet. 2016; 387; 10018: 545-557. 1:CAS:528:DC%2BC2MXhvV2jsrzF. 10.1016/S0140-6736(15)00986-1. 26615328</bibtext> </blist> <blist> <bibtext> Wu B, Gu X, Zhang Q. Cost-Effectiveness of osimertinib for EGFR mutation-positive non-small cell lung cancer after progression following first-line EGFR TKI therapy. J. Thorac. Oncol. 2018; 13; 2: 184-193. 1:CAS:528:DC%2BC1MXhsleks7vK. 10.1016/j.jtho.2017.10.012. 29101057</bibtext> </blist> <blist> <bibtext> Association CP. China Guidelines for Pharmacoeconomic Evaluations. 2019. https://www.cpa.org.cn//?do=infoandcid=75017. Accessed 11 June 2023.</bibtext> </blist> <blist> <bibtext> Rini BI, Plimack ER, Stus V. Pembrolizumab plus axitinib versus sunitinib for advanced renal-cell carcinoma. New Engl. J. Med. 2019; 380; 12: 1116-1127. 1:CAS:528:DC%2BC1MXntVKis7w%3D. 10.1056/NEJMoa1816714. 30779529</bibtext> </blist> <blist> <bibtext> Kohn CG, Zeichner SB, Chen Q, Montero AJ, Goldstein DA, Flowers CR. Cost-effectiveness of immune checkpoint inhibition in BRAF wild-type advanced melanoma. J. Clin. Oncol. 2017; 35; 11: 1194-1202. 1:CAS:528:DC%2BC1cXktFGrt7k%3D. 10.1200/JCO.2016.69.6336. 28221865. 5791832</bibtext> </blist> <blist> <bibtext> Tikhonova IA, Huxley N, Snowsill T. Economic analysis of first-line treatment with cetuximab or panitumumab for RAS wild-type metastatic colorectal cancer in England. PharmacoEconomics. 2018; 36; 7: 837-851. 10.1007/s40273-018-0630-9. 29498000</bibtext> </blist> <blist> <bibtext> Wan XM, Peng LB, Ma JA, Li YJ. Economic evaluation of nivolumab as a second-line treatment for advanced renal cell carcinoma from US and Chinese perspectives. Cancer. 2017; 123; 14: 2634-2641. 1:CAS:528:DC%2BC2sXhtFSms7fF. 10.1002/cncr.30666. 28301684. 1498.60109</bibtext> </blist> <blist> <bibtext> Liao W, Huang J, Zhu G. S-1 or gemcitabine adjuvant therapy in resected pancreatic cancer: A cost-effectiveness analysis based on the JASPAC-01 trial. Expert Rev. Pharmacoecon. Outcomes Res. 2020; 20; 1: 133-138. 10.1080/14737167.2020.1677155. 31597496</bibtext> </blist> <blist> <bibtext> Zhou J, Zhao R, Wen F. Cost-effectiveness analysis of gemcitabine, S-1 and gemcitabine plus S-1 for treatment of advanced pancreatic cancer based on GEST study. Med. Oncol. 2015; 32; 4: 121. 10.1007/s12032-015-0580-4. 25788034. 1150.91317</bibtext> </blist> <blist> <bibtext> Zhu Y, Liu K, Ding D, Zhou Y, Peng L. Pembrolizumab plus chemotherapy as first-line treatment for advanced esophageal cancer: A cost-effectiveness analysis. Adv. Ther. 2022; 39; 6: 2614-2629. 10.1007/s12325-022-02101-9. 35394255. 1509.93021</bibtext> </blist> <blist> <bibtext> Zhu Y, Liu K, Ding D, Wang K, Liu X, Tan X. Chemo-immunotherapy regimes for recurrent or metastatic nasopharyngeal carcinoma: A network meta-analysis and cost-effectiveness analysis. Front. Pharmacol. 2022; 13. 1:CAS:528:DC%2BB38XhsFent7bN. 10.3389/fphar.2022.858207. 35668931. 9163401858207</bibtext> </blist> <blist> <bibtext> Li N, Zheng H, Huang Y, Zheng B, Cai H, Liu M. Cost-effectiveness analysis of olaparib maintenance treatment for germline BRCA-mutated metastatic pancreatic cancer. Front. Pharmacol. 2021; 12. 1:CAS:528:DC%2BB3MXhvVWmsr7P. 10.3389/fphar.2021.632818. 33959007. 8096350632818</bibtext> </blist> <blist> <bibtext> Wu B, Li T, Cai J, Xu Y, Zhao G. Cost-effectiveness analysis of adjuvant chemotherapies in patients presenting with gastric cancer after D2 gastrectomy. BMC Cancer. 2014; 14: 984. 10.1186/1471-2407-14-984. 25526802. 4301844. 1451.28003</bibtext> </blist> <blist> <bibtext> Cai H, Xu B, Li N, Zheng B, Zheng Z, Liu M. Cost-effectiveness analysis of camrelizumab versus chemotherapy as second-line treatment of advanced or metastatic esophageal squamous cell carcinoma. Front. Pharmacol. 2021; 12. 10.3389/fphar.2021.732912. 34867339. 8634950732912</bibtext> </blist> <blist> <bibtext> Wan X, Zhang Y, Tan C, Zeng X, Peng L. First-line nivolumab plus ipilimumab vs. sunitinib for metastatic renal cell carcinoma: A cost-effectiveness analysis. JAMA Oncol. 2019; 5; 4: 491-496. 10.1001/jamaoncol.2018.7086. 30789633. 6459127</bibtext> </blist> <blist> <bibtext> Hoyle M, Green C, Thompson-Coon J. Cost-effectiveness of temsirolimus for first line treatment of advanced renal cell carcinoma. Value Health. 2010; 13; 1: 61-68. 10.1111/j.1524-4733.2009.00617.x. 19804430</bibtext> </blist> <blist> <bibtext> Morimoto K, Moriwaki K, Kaneyasu T, Nakayama H, Shimozuma K. Cost-effectiveness of nab-paclitaxel and gemcitabine versus gemcitabine monotherapy for patients with unresectable metastatic pancreatic cancer in Japan. Value Health Reg. Issues. 2022; 28: 54-60. 10.1016/j.vhri.2021.04.003. 34800832</bibtext> </blist> <blist> <bibtext> Cui J, Zhang X, Qu S, Wang L. Cost-effectiveness analysis of nab-paclitaxel plus gemcitabine versus folfirinox in the treatment of metastatic pancreatic cancer in china. Expert Rev. Pharmacoecon. Outcomes Res. 2021; 21; 4: 691-697. 10.1080/14737167.2020.1812386. 32976031</bibtext> </blist> <blist> <bibtext> Kang J, Hwang I, Yoo C. Nab-paclitaxel plus gemcitabine versus FOLFIRINOX as the first-line chemotherapy for patients with metastatic pancreatic cancer: Retrospective analysis. Investig. New Drugs. 2018; 36; 4: 732-741. 1:CAS:528:DC%2BC1cXmvFaqurw%3D. 10.1007/s10637-018-0598-5</bibtext> </blist> <blist> <bibtext> Bao K, Li X, He X, Jian L. Pharmacoeconomic evaluation of erlotinib for the treatment of pancreatic cancer. Clin. Ther. 2021; 43; 6: 1107-1115. 1:CAS:528:DC%2BB3MXhvVGgsrjN. 10.1016/j.clinthera.2021.04.012. 34059328. 1449.20020</bibtext> </blist> <blist> <bibtext> Moore MJ, Goldstein D, Hamm J. Erlotinib plus gemcitabine compared with gemcitabine alone in patients with advanced pancreatic cancer: A phase III trial of the national cancer institute of Canada clinical trials group. J. Clin. Oncol. 2007; 25; 15: 1960-1966. 1:CAS:528:DC%2BD2sXmvVWmsr0%3D. 10.1200/JCO.2006.07.9525. 17452677</bibtext> </blist> <blist> <bibtext> Xiao J, Sun JF, Wang QQ, Qi X, Yao HY. Health economic evaluation reporting guideline and application status. Zhonghua yu fang yi xue za zhi [Chinese journal of preventive medicine]. 2017; 51; 3: 276-280. 1:STN:280:DC%2BC1czivV2hsw%3D%3D. 28260345. 1105.94327</bibtext> </blist> <blist> <bibtext> Wilson DL. The analysis of survival (mortality) data: Fitting Gompertz, Weibull, and logistic functions. Mech. Ageing Dev. 1994; 74; 1–2: 15-33. 1:STN:280:DyaK2M%2FhvFymtw%3D%3D. 10.1016/0047-6374(94)90095-7. 7934205. 52.0605.21</bibtext> </blist> </ref> <aug> <p>Reported by Author; Author; Author</p> </aug> <nolink nlid="nl1" bibid="bib466" firstref="ref1"></nolink> <nolink nlid="nl2" bibid="bib496" firstref="ref2"></nolink> <nolink nlid="nl3" bibid="bib10" firstref="ref17"></nolink> <nolink nlid="nl4" bibid="bib11" firstref="ref18"></nolink> <nolink nlid="nl5" bibid="bib12" firstref="ref19"></nolink> <nolink nlid="nl6" bibid="bib13" firstref="ref20"></nolink> <nolink nlid="nl7" bibid="bib14" firstref="ref21"></nolink> <nolink nlid="nl8" bibid="bib15" firstref="ref22"></nolink> <nolink nlid="nl9" bibid="bib16" firstref="ref23"></nolink> <nolink nlid="nl10" bibid="bib17" firstref="ref24"></nolink> <nolink nlid="nl11" bibid="bib18" firstref="ref25"></nolink> <nolink nlid="nl12" bibid="bib19" firstref="ref26"></nolink> <nolink nlid="nl13" bibid="bib20" firstref="ref28"></nolink> <nolink nlid="nl14" bibid="bib21" firstref="ref29"></nolink> <nolink nlid="nl15" bibid="bib22" firstref="ref30"></nolink> <nolink nlid="nl16" bibid="bib23" firstref="ref31"></nolink> <nolink nlid="nl17" bibid="bib24" firstref="ref32"></nolink> <nolink nlid="nl18" bibid="bib25" firstref="ref34"></nolink> <nolink nlid="nl19" bibid="bib26" firstref="ref37"></nolink> <nolink nlid="nl20" bibid="bib27" firstref="ref38"></nolink> <nolink nlid="nl21" bibid="bib28" firstref="ref39"></nolink> <nolink nlid="nl22" bibid="bib29" firstref="ref40"></nolink> <nolink nlid="nl23" bibid="bib30" firstref="ref41"></nolink> <nolink nlid="nl24" bibid="bib31" firstref="ref42"></nolink> <nolink nlid="nl25" bibid="bib32" firstref="ref43"></nolink>
CustomLinks:
  – Url: https://resolver.ebsco.com/c/xy5jbn/result?sid=EBSCO:edsdoj&genre=article&issn=20452322&ISBN=&volume=15&issue=1&date=20250201&spage=1&pages=1-9&title=Scientific Reports&atitle=Cost-effectiveness%20analysis%20of%20nimotuzumab%20combined%20with%20gemcitabine%20for%20K-Ras%20wild%20type%20locally%20advanced%20or%20metastatic%20pancreatic%20cancer%20in%20China&aulast=Rong%20Long&id=DOI:10.1038/s41598-025-90960-x
    Name: Full Text Finder (for New FTF UI) (s8985755)
    Category: fullText
    Text: Find It @ SCU Libraries
    MouseOverText: Find It @ SCU Libraries
  – Url: https://doaj.org/article/9f472f9a4b074ff5ae8d95d9ac1c8e58
    Name: EDS - DOAJ (s8985755)
    Category: fullText
    Text: View record from DOAJ
    MouseOverText: View record from DOAJ
Header DbId: edsdoj
DbLabel: Directory of Open Access Journals
An: edsdoj.9f472f9a4b074ff5ae8d95d9ac1c8e58
RelevancyScore: 1082
AccessLevel: 3
PubType: Academic Journal
PubTypeId: academicJournal
PreciseRelevancyScore: 1081.56311035156
IllustrationInfo
Items – Name: Title
  Label: Title
  Group: Ti
  Data: Cost-effectiveness analysis of nimotuzumab combined with gemcitabine for K-Ras wild type locally advanced or metastatic pancreatic cancer in China
– Name: Author
  Label: Authors
  Group: Au
  Data: <searchLink fieldCode="AR" term="%22Rong+Long%22">Rong Long</searchLink><br /><searchLink fieldCode="AR" term="%22Hao+Guo%22">Hao Guo</searchLink><br /><searchLink fieldCode="AR" term="%22Kun+Chen%22">Kun Chen</searchLink>
– Name: TitleSource
  Label: Source
  Group: Src
  Data: Scientific Reports, Vol 15, Iss 1, Pp 1-9 (2025)
– Name: Publisher
  Label: Publisher Information
  Group: PubInfo
  Data: Nature Portfolio, 2025.
– Name: DatePubCY
  Label: Publication Year
  Group: Date
  Data: 2025
– Name: Subset
  Label: Collection
  Group: HoldingsInfo
  Data: LCC:Medicine<br />LCC:Science
– Name: Subject
  Label: Subject Terms
  Group: Su
  Data: <searchLink fieldCode="DE" term="%22K-Ras+wild+type%22">K-Ras wild type</searchLink><br /><searchLink fieldCode="DE" term="%22Locally+advanced+or+metastatic+pancreatic+cancer%22">Locally advanced or metastatic pancreatic cancer</searchLink><br /><searchLink fieldCode="DE" term="%22Nimotuzumab%22">Nimotuzumab</searchLink><br /><searchLink fieldCode="DE" term="%22Gemcitabine%22">Gemcitabine</searchLink><br /><searchLink fieldCode="DE" term="%22Cost-effectiveness%22">Cost-effectiveness</searchLink><br /><searchLink fieldCode="DE" term="%22First-line+treatment%22">First-line treatment</searchLink><br /><searchLink fieldCode="DE" term="%22Medicine%22">Medicine</searchLink><br /><searchLink fieldCode="DE" term="%22Science%22">Science</searchLink>
– Name: Abstract
  Label: Description
  Group: Ab
  Data: Abstract The phase III NOTABLE trial has revealed that nimotuzumab plus gemcitabine achieves greater clinical benefit in the first-line treating K-Ras wild type locally advanced (LA) or metastatic pancreatic cancer (mPC), compared to gemcitabine. Hence, herein, we examined the cost-efficiency of introducing nimotuzumab to gemcitabine, relative to gemcitabinealone, in first-line K-Ras wild type LA or mPC therapy from a Chinese payer perspective. We generated an exhaustive decision-analytical Markov model using three exclusive health states to incorporate both clinical and economic consequences of nimotuzumab plus gemcitabine versus gemcitabine alone as first-line therapy patients with K-Ras wild type LA or mPC. Using a 10-year lifetime horizon, we assessed the total medical expenditure, quality-adjusted life years (QALYs), and incremental cost‒effectiveness ratio (ICER) as the primary surrogate outcomes of our model. Sensitivity analyses were conducted via alteration of internally tweakable parameters, and further subgroup analyses were conducted as needed. The overall health surrogate outcomes were 2.94 QALYs ($215,799) among patients with nimotuzumab plus gemcitabine and 1.83 QALYs ($86,039) among patients with gemcitabine alone (ICER value, $117,263/QALY; Incremental net health benefit [INHB] value, − 2.46/QALY). Based on our sensitivity analysis, among all parameters, progression-free survival (PFS) utility was of utmost importance, and it exerted a considerable impact on our model. The ICER consistently well exceeded the willingness-to-pay (WTP) threshold and negative INHBs were observed across all patient subcategories with zero alteration recorded as cost-effective in the subgroup analyses. Nimotuzumab plus gemcitabine, relative to gemcitabine alone, is not a cost-effective first-line treatment among patients with K-Ras wild type LA or mPC at the current prices offered in China.
– Name: TypeDocument
  Label: Document Type
  Group: TypDoc
  Data: article
– Name: Format
  Label: File Description
  Group: SrcInfo
  Data: electronic resource
– Name: Language
  Label: Language
  Group: Lang
  Data: English
– Name: ISSN
  Label: ISSN
  Group: ISSN
  Data: 2045-2322
– Name: NoteTitleSource
  Label: Relation
  Group: SrcInfo
  Data: https://doaj.org/toc/2045-2322
– Name: DOI
  Label: DOI
  Group: ID
  Data: 10.1038/s41598-025-90960-x
– Name: URL
  Label: Access URL
  Group: URL
  Data: <link linkTarget="URL" linkTerm="https://doaj.org/article/9f472f9a4b074ff5ae8d95d9ac1c8e58" linkWindow="_blank">https://doaj.org/article/9f472f9a4b074ff5ae8d95d9ac1c8e58</link>
– Name: AN
  Label: Accession Number
  Group: ID
  Data: edsdoj.9f472f9a4b074ff5ae8d95d9ac1c8e58
PLink https://login.libproxy.scu.edu/login?url=https://search.ebscohost.com/login.aspx?direct=true&site=eds-live&scope=site&db=edsdoj&AN=edsdoj.9f472f9a4b074ff5ae8d95d9ac1c8e58
RecordInfo BibRecord:
  BibEntity:
    Identifiers:
      – Type: doi
        Value: 10.1038/s41598-025-90960-x
    Languages:
      – Text: English
    PhysicalDescription:
      Pagination:
        PageCount: 9
        StartPage: 1
    Subjects:
      – SubjectFull: K-Ras wild type
        Type: general
      – SubjectFull: Locally advanced or metastatic pancreatic cancer
        Type: general
      – SubjectFull: Nimotuzumab
        Type: general
      – SubjectFull: Gemcitabine
        Type: general
      – SubjectFull: Cost-effectiveness
        Type: general
      – SubjectFull: First-line treatment
        Type: general
      – SubjectFull: Medicine
        Type: general
      – SubjectFull: Science
        Type: general
    Titles:
      – TitleFull: Cost-effectiveness analysis of nimotuzumab combined with gemcitabine for K-Ras wild type locally advanced or metastatic pancreatic cancer in China
        Type: main
  BibRelationships:
    HasContributorRelationships:
      – PersonEntity:
          Name:
            NameFull: Rong Long
      – PersonEntity:
          Name:
            NameFull: Hao Guo
      – PersonEntity:
          Name:
            NameFull: Kun Chen
    IsPartOfRelationships:
      – BibEntity:
          Dates:
            – D: 01
              M: 02
              Type: published
              Y: 2025
          Identifiers:
            – Type: issn-print
              Value: 20452322
          Numbering:
            – Type: volume
              Value: 15
            – Type: issue
              Value: 1
          Titles:
            – TitleFull: Scientific Reports
              Type: main
ResultId 1