Skip to main content
Download PDF
Download ePub

Economic evaluation of NALIRIFOX vs. nab-paclitaxel and gemcitabine regimens for first-line treatment of metastatic pancreatic ductal adenocarcinoma from U.S. perspective

Cost Effectiveness and Resource Allocation volume 22, Article number: 70 (2024) Cite this article

Abstract

Background

The cost-effectiveness of NALIRIFOX as a potential new standard of care for patients with metastatic pancreatic ductal adenocarcinoma (mPDAC) has yet to be established. Our objective was to evaluate the cost-effectiveness of NALIRIFOX vs. nab-paclitaxel and gemcitabine in this indication from the perspective of U.S. public payers.

Methods

A partitioned survival model was constructed from the perspective of U.S. public payers, drawing on baseline patient characteristics and vital clinical data from the NAPOLI-3 trial. Costs and utilities were sourced from publicly accessible databases and literature. A lifetime horizon was applied, with an annual discount rate of 3%. We calculated and compared cumulative costs, life years, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios (ICER). To evaluate the model’s robustness, sensitivity analyses, scenario analyses, and subgroup analyses were carried out. Additionally, a price simulation for the costly liposomal irinotecan was conducted to inform the pricing strategy at the given willingness to pay (WTP) threshold.

Results

In the base-case analysis, NALIRIFOX provided an additional 0.29 QALYs with an ICER of $206,340.69 /QALY compared to nab-paclitaxel and gemcitabine, indicating it is not cost-effective at a $150,000/QALY threshold. Sensitivity analysis showed the model was most sensitive to the costs of liposomal irinotecan, capecitabine, and post-progression care. Probabilistic sensitivity analysis indicated a 17.66% probability of NALIRIFOX being cost-effective at $150,000/QALY, rising to 47.48% at $200,000/QALY. Pricing simulations suggested NALIRIFOX could become cost-effective at $150,000/QALY if the price of irinotecan liposome drops to $53.24/mg (a 14.8% reduction).

Conclusions

NALIRIFOX may not be cost-effective at its current price as a first-line treatment for patients with mPDAC in the long term. The cost of liposomal irinotecan has the greatest impact. It may become cost-effective only if its cost is reduced by 14.8%, with a WTP threshold of $150,000 /QALY.

Introduction

Metastatic pancreatic ductal adenocarcinoma (mPDAC) remains one of the most lethal forms of cancer, with a 5-year survival rate below 10% [1] It is the fourth leading cause of cancer-related mortality in the United States, with projections placing it as the second leading cause by 2030 [2, 3]. This alarming trend underscores the imperative need for novel and more efficacious treatment strategies. Despite significant advancements in the understanding of the pathophysiology of mPDAC over recent decades, breakthroughs in clinical treatment strategies are still lacking, with the therapeutic effects of existing regimens being relatively limited. Currently, two combination chemotherapy regimens are the standard first-line treatments for mPDAC: the FOLFIRINOX, which is a combination of fluorouracil, leucovorin, irinotecan, and oxaliplatin, and the doublet regimen of nab-paclitaxel with gemcitabine [4].

Liposomal irinotecan represents an innovative approach in cancer treatment, encapsulating the topoisomerase I inhibitor irinotecan within a lipid bilayer vesicle to prolong its circulation time before it is converted to its active metabolite [5]. A phase 1/2 trial (NCT02551991, which was initially registered on ClinicalTrials.gov on September 16, 2015) that explored the combination of liposomal irinotecan with fluorouracil, leucovorin, and oxaliplatin, known as NALIRIFOX, demonstrated promising antitumor activity in treatment-naive patients with mPDAC [6]. The subsequent international randomized phase III trial, NAPOLI-3 [7], assessed the efficacy and safety of NALIRIFOX in comparison to the standard doublet regimen of nab-paclitaxel and gemcitabine for patients who had not previously received treatment for metastatic PDAC. The survival analysis revealed a median overall survival of 11.1 months with NALIRIFOX, which was significantly longer than the 9.2 months recorded for the doublet chemotherapy group. The risk of death was reduced by 17% for patients receiving NALIRIFOX, with progression-free survival times of 7.4 months compared to 5.6 months for the doublet regimen. Building upon the observed superior efficacy, the NALIRIFOX regimen was formally incorporated into the first-line treatment recommendations for pancreatic cancer in the 2023 V2 edition of the National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines [8]. In February 2024, the U.S. Food and Drug Administration (FDA) approved NALIRIFOX regimen as a potential first-line treatment for mPDAC [9].

Despite these promising clinical outcomes, the cost of liposomal irinotecan, at $62.485 for 1 mg, is substantially higher than that of regular irinotecan, which is $2.064 for 20 mg, raising concerns about its cost-effectiveness [10, 11]. To date, there has been an absence of pharmacoeconomic evaluations concerning this issue. Therefore, our study aimed to compare the cost-effectiveness of NALIRIFOX versus the combination of nab-paclitaxel and gemcitabine as first-line therapy for previously untreated mPDAC patients, from the perspective of U.S. public insurance payers.

Methods

Study design

This study adhered to the Consolidated Health Economic Evaluation Reporting Standards reporting guideline (Supplement 1) [12]. The target population comprised adult patients in the United States with pancreatic ductal adenocarcinoma who were previously untreated in the metastatic setting. It was assumed that these patients shared similar baseline characteristics with those enrolled in the NAPOLI-3 trial (baseline information is detailed in Supplement 2 Table S1). Additionally, our model presumed a body surface area of 1.79m2 for the hypothetical patient cohort [13].

Patients were allocated to either the NALIRIFOX regimen or the standard chemotherapy regimen. The NALIRIFOX arm consisted of liposomal irinotecan at a dose of 50mg/m2, oxaliplatin at 60mg/m2, leucovorin at 400mg/m2, and fluorouracil at 2400mg/m2, administered sequentially as a continuous intravenous infusion over 46 h on days 1 and 15 of a 28-day cycle. The comparator arm was treated with nab-paclitaxel at a dose of 125mg/m2 and gemcitabine at 1000 mg/m2. The proportions of the subsequent treatments as reported in the NAPOLI-3 trial, and the first-line progressive treatment protocol was reference to NCT00112658 [14]. It was assumed that patients in the NALIRIFOX arm, upon disease progression, would be treated with monotherapy gemcitabine at a dose of 1000 mg/m2 administered via injection on days 1, 8, and 15 throughout four consecutive cycles. In contrast, patients in the nab-paclitaxel and gemcitabine arm, upon progression, would receive the FOLFIRINOX regimen, which includes oxaliplatin at 85 mg/m2 administered intravenously over 2 hours, leucovorin at 400 mg/m2 also administered intravenously over 2 hours, irinotecan at 180 mg/m2, followed by a 400 mg/m2 bolus of fluorouracil.

Model structure

We developed a partitioned survival model to compare the cost and effectiveness of the NALIRIFOX regimen versus the Nab-paclitaxel and Gemcitabine regimens as first-line treatments for mPDAC. The model delineated three mutually exclusive health states: progression-free survival (PFS), progressed disease (PD), and death (Fig. 1). The time horizon of the model was established from a lifetime perspective, meaning that 99% of the patients would have transitioned to the death state. The cycle length was defined as one treatment cycle, which was 28 days. This analysis was conducted from the perspective of U.S. public payers (Medicare).

Fig. 1
figure 1

Partitioned survival model structure

Full size image

The primary outcomes of the model were costs, life years (LYs), equal value of life years gained (evLYG), quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios (ICER). Both costs and utilities were discounted at an annual rate of 3%. The willingness-to-pay (WTP) threshold considered the common U.S. benchmark of $150,000 /QALY gained, as well as a higher threshold of $200,000 /QALY for metastatic cancer [15]. The modeling and analysis were carried out using R version 4.3.0, available at R Project for Statistical Computing, and Microsoft Excel. Within the R environment, we used the“flexsurv” and “survHE” packages to reconstruct individual patient data (IPD) and extrapolate survival outcomes.

Effectiveness

Probabilities of PFS and OS were extracted from Kaplan-Meier curves from NAPOLI-3 through Engauge Digitizer (version 4.1) by Guyot’s method to reconstruct estimates of IPD [16]. Reconstructed IPD comprised event and censor times and were almost equal in number to the initial number at risk, which closely reproduced the digitized Kaplan-Meier curves. The reconstructed IPD was then used to fit the following survival functions: exponential, Weibull, Gompertz, gamma, log-logistic, log-normal, generalized gamma, fractional polynomial, restricted cubic spline models, and Royston-Parmar spline models. The goodness of fit was evaluated through the Akaike information criterion (AIC) and visual inspection. Lower AIC value combined with practical visual effect indicated a better fit of the selected model. Further information on the methodology of the goodness of fit and external validation can be found in Supplement 2 Table S2 and Figure S1.

Cost and utility

The economic model considered direct medical costs such as the cost of acquiring drugs, cost of follow-up, cost of treatment of adverse events (AEs), best supportive care, and end-of-life care. The drug costs were based on prices from Medicare Part B [17]. Given the potential overlap in the statistical categorization of AEs at different levels, to avoid double, and the model specifically considered AEs (Grade 3 or higher) with incidence rates exceeding 2%. The associated costs and durations of these AEs were extracted from data reported in published literature. To ensure the cost estimations were current and reflective of the study’s time frame, all prices were adjusted for inflation to October 2023 values using the Consumer Price Index Inflation Calculator [17, 18].

The utility values for PFS and PD were obtained from a U.S. economic evaluation of systemic chemotherapy as a first-line treatment for metastatic pancreatic cancer [15]. The disutilities due to AEs considered in this analysis were extracted from other studies. All AEs were assumed to be incurred during the first cycle; the duration-adjusted disutilities were subtracted from the baseline values. The parameters of model input are shown in Table 1.

Table 1 Model input parameters
Full size table

Sensitivity analysis

To evaluate the stability of the outcomes from the base-case analysis, sensitivity analyses were executed. The deterministic sensitivity analysis (DSA) involved modulating all parameters within their 95% confidence intervals or by ranging plausible variations (± 20%) from the base-case estimates. For the cost parameters, a gamma distribution was chosen, while a beta distribution was applied to the probability, proportion, and utility estimates. The probabilistic sensitivity analysis (PSA) was then carried out for the stipulated price point by undertaking 10,000 Monte Carlo simulation iterations. The cost-effectiveness acceptability curve (CEAC) was utilized to determine the cost-effectiveness of each treatment regimen across a range of WTP thresholds.

Scenario analysis

Due to the significant cost variability and associated uncertainty that subsequent treatment may influence the outcomes, we conducted a scenario analysis for second-line therapy approaches. We incorporated second-line treatment regimens for pancreatic cancer as recommended by the NCCN and European Society for Medical Oncology guidelines [19], as well as those reported in NAPOLI-3 (Supplement 2 Table S3). To account for different patient scenarios in subsequent lines of therapy and to minimize the uncertainty of the results, we selected the highest and lowest cycle cost scenarios from the second-line treatment options for the NALIRIFOX group and the Nab-paclitaxel and gemcitabine group. This approach allowed us to construct an analysis consisting of four distinct scenarios. The scenarios are as follows, Scenario 1: NALIRIFOX followed by gemcitabine with nab-paclitaxel and gemcitabine followed by FOLFIRINOX. Scenario 2: NALIRIFOX followed by gemcitabine with nab-paclitaxel and gemcitabine followed by 5-FU, leucovorin, and liposomal irinotecan. Scenario 3: NALIRIFOX followed by mFOLFOX with nab-paclitaxel and gemcitabine followed by FOLFIRINOX. Scenario 4: NALIRIFOX followed by mFOLFOX with nab-paclitaxel and gemcitabine followed by 5-FU, leucovorin, and liposomal irinotecan.

Subgroup analysis

In the subgroup analysis, the ICER was calculated using the subgroup-specific HRs for PFS and OS obtained from NAPOLI-3. Subgroup analyses were conducted under WTP thresholds of $200,000 and $150,000 for the US scenarios. We considered the subgroups of patients of different age (< 65 or ≥ 65), sex (male or female), Eastern Cooperative Oncology Group performance status score (0 or 1), white race, region (North America or rest of the world), number of metastatic sites (1, 2 or ≥ 3), presence of liver metastases at baseline (yes or no), main pancreatic tumor location (head or other), and baseline CA 19 − 9 (< 37 U/ml or ≥ 37 U/ml).

Price simulation

Considering the high cost of liposomal irinotecan, we conducted a price simulation by varying the price of irinotecan liposome (1 mg) between $10 and $63 to analyze the possibility of cost-effectiveness of the NALIRIFOX regimen at U.S. willingness-to-pay thresholds of $150,000/QALY and $200,000/QALY.

Results

Base case analysis

The base-case analysis results, presented in Table 2, revealed that the lifetime treatment cost for NALIRIFOX is $216,397.03, which was substantially higher than the lifetime costs for the regimen of nab-paclitaxel and Gemcitabine, calculated at $156,558.23. The NALIRIFOX regimen resulted in an increase of 0.44 evLYG and 0.29 QALYs compared to the nab-paclitaxel and Gemcitabine regimen. However, the ICER for NALIRIFOX in comparison to nab-paclitaxel and Gemcitabine was determined to be $206,340.69 /QALY, which was higher than the chosen WTP threshold of $150,000 /QALY.

Table 2 Results of base-case analysis
Full size table

Sensitivity analysis

The results of the DSA are shown in Fig. 2. The primary factors influencing the ICER were determined to be the cost of liposomal irinotecan, the cost of capecitabine, and the follow-up cost post-progression per cycle. This is attributed to the fact that liposomal irinotecan is a key component of the NALIRIFOX regimen and carries a relatively high baseline price. Consequently, fluctuations in the price of liposomal irinotecan have the most significant impact on the ICER results. In addition to the cost of liposomal irinotecan, the cost of capecitabine and the follow-up costs after progression emerged as critical determinants of the ICER. These factors are significant components of the second-line treatment and have a substantial impact on the overall cost of the treatment regimen. Given that capecitabine and carboplatin are significant components of the primary treatment options for patients after first-line therapy progression, variations in their costs also had a considerable effect on the ICER. Overall, after accounting for parameter variations within their specified ranges, it was concluded that NALIRIFOX was rarely cost-effective at the WTP threshold of $200,000 /QALY or $150,000 /QALY.

Fig. 2
figure 2

Tornado diagram shows the association of variables with the ICER of NALIRIFOX vs. nab-paclitaxel and gemcitabine. Abbreviation: ICER incremental cost-effectiveness ratio, QALY quality-adjusted life year

Full size image

The cost-effectiveness density scatter plot is shown in Fig. 3A. The PSA results indicated that the average cost for NALIRIFOX was $211,568, while that for nab-paclitaxel and gemcitabine was $153,426. The average health outcomes were quantified as 0.94 and 0.65 QALYs for these respective treatments. At a WTP threshold of $150,000 /QALY, the probability of NALIRIFOX being cost-effective was 17.66%. When the threshold increased to $200,000 /QALY, this probability rose to 47.48% (Fig. 3B).

Fig. 3
figure 3

Results of the probabilistic sensitivity analysis (A. Cost-effectiveness scatter plot; B. Cost-Effectiveness Acceptability Curve). Note: Different colors in the cost-effectiveness scatter plot represent point density in that area

Full size image

Scenario analysis

The scenario analysis compared the ICER of NALIRIFOX and nab-paclitaxel and gemcitabine under different combinations of subsequent treatment regimens (Supplement 2 Table S4). The scenario analysis showed that scenario 1 and scenario 3 resulted in an ICER of $206,340 /QALY and $248,519 /QALY, respectively. This means that even the higher WTP threshold of $200,000 /QALY would not be cost-effective. This outcome may be because the most expensive subsequent treatment regimen was chosen for use after the NALIRIFOX protocol, while the least expensive subsequent treatment regimen was utilized following the nab-paclitaxel and gemcitabine protocol, resulting in the lack of cost-effectiveness for NALIRIFOX. In the other scenarios, NALIRIFOX was found to be cost-effective. Therefore, the choice of subsequent treatment regimens had a significant impact on the cost-effectiveness of the frontline treatment strategies.

Subgroup analysis

Summary results of the subgroup analysis are presented in Supplement 2 Table S5. At a WTP threshold of $150,000 /QALY, the subgroup with the highest probability of being cost-effective was the North America subgroup (17.4%), followed by the subgroup with a baseline ECOG performance status of 1 (17.0%). A similar trend was observed at a WTP threshold of $200,000 /QALY.

Price simulation

The results of the price simulation are presented in Supplement 2 Figure S2. As the price of irinotecan liposome (1 mg) fluctuated between $10 and $63, the ICER increased in tandem with the rising cost of irinotecan liposome. NALIRIFOX becomes cost-effective at an irinotecan liposome price of $53.24/mg (a 14.8% reduction) when considering a WTP threshold of $150,000 /QALY. For a WTP threshold of $200,000 /QALY, the irinotecan liposome price of $60.83/mg (a 2.7% reduction) is required for cost-effectiveness.

Discussion

With the rising costs of healthcare, the emphasis on value in oncology care is becoming increasingly pertinent. The NAPOLI-3 trial’s promising results suggest that NALIRIFOX may represent a significant advancement in the treatment of metastatic pancreatic ductal adenocarcinoma (mPDAC), offering potential therapeutic gains and an improved safety profile compared to the existing nab-paclitaxel and gemcitabine regimen. Recognizing its therapeutic promise, the FDA granted approval to NALIRIFOX in February 2024 as a primary treatment option for mPDAC. However, the lack of comprehensive pharmacoeconomic evaluations has left clinicians and patients uncertain about the cost-effectiveness of NALIRIFOX.

Previous research in the U.S. context has been limited. For instance, Bin Wu et al. [20] analyzed the cost-effectiveness of olaparib maintenance therapy for metastatic pancreatic cancer with BRCA mutations, using a partitioned survival model. The study concluded that olaparib was cost-effective at a $200,000 /QALY WTP threshold, based on PFS benefits alone, given no OS advantage over placebo. Similarly, Mahdi Gharaibeh’s evaluation [15], using a Markov model, found that combination therapies for mPDAC, including oxaliplatin + gemcitabine, capecitabine + gemcitabine, FOLFIRINOX, and nab-paclitaxel + gemcitabine, surpassed gemcitabine monotherapy ineffectiveness at the same WTP threshold, with nab-paclitaxel + gemcitabine being the most cost-effective. However, there has been a lack of recent evidence on the cost-effectiveness of NALIRIFOX.

To the best of our knowledge, this is the inaugural evaluation of the cost-effectiveness of NALIRIFOX as a first-line therapy for mPDAC from the standpoint of U.S. public payer. The strength of this research lies in its comprehensive approach, which includes evaluating various second-line treatment scenarios and conducting extensive sensitivity analyses. Moreover, we performed pricing simulations for irinotecan liposome, furnishing policymakers with more comprehensive evidence. Finally, we included economic information from 18 subgroups according to the NAPOLI-3, offering insights into tailoring treatment choices in the era of precision medicine.

Despite these strengths, there are several limitations to our study. First, due to constraints in the original clinical trial, our analysis may be subject to inherent biases. For example, the proportions of subsequent treatments were only reported as single agents, which could introduce errors in calculating subsequent treatment costs. Additional clinical data would be necessary to enhance the accuracy of this study. Second, the utilities used in our model were not derived from the NAPOLI-3 trial but were instead sourced from a published health technology assessment. We assumed identical utilities for patients in both groups, which may have introduced bias into the results. Utilizing utility values from other related RCTs rather than directly from NAPOLI-3 presents several potential issues. Patient populations in different trials often have varying baseline characteristics, disease severities, and responses to treatment, all of which can significantly influence health-related quality of life. As a result, utility values from these external RCTs may not fully reflect the specific experiences of patients in the NAPOLI-3 trial. Additionally, differences in study design—such as variations in follow-up duration, assessment tools, and health state definitions—can lead to inconsistencies in utility values, potentially resulting in estimates that are not entirely comparable or representative of the outcomes within the context of NAPOLI-3. While the use of external utility values is sometimes necessary, it is important to acknowledge these limitations and carefully consider the potential biases they may introduce when interpreting the model’s results. Furthermore, one concern that arose during the modeling process was the potential for overfitting, particularly given the high mortality rate associated with mPDAC. While our analysis ensured that the fitted survival curves did not fall below the prevailing age-specific all-cause mortality rate, this criterion alone may not be sufficient to completely rule out overfitting. Finally, in the context of our scenario analysis, it is important to note that the NAPOLI-3 clinical trial has limitations, particularly in that post-progression survival outcomes are already established. While we acknowledge that simplifying the post-treatment scenario may appear reductive, adjusting the survival curves to reflect these changes is unfortunately not feasible within the scope of our current analysis.

It is also essential to address the limitations of using QALY as a measure. One of the primary concerns is its potential to be discriminatory, particularly in the context of diseases with limited survival benefits, such as metastatic cancer. QALY has been criticized for potentially undervaluing the lives of individuals with chronic conditions or disabilities, as it combines both the quantity and quality of life into a single metric. This can lead to biases in health economic evaluations, especially when comparing treatments for populations with different baseline health states [21]. Moreover, recent developments, such as the rules outlined in the Inflation Reduction Act, have highlighted the potential discriminatory nature of QALY, and the Act has ruled out QALY as a relevant metric in certain contexts, reflecting growing concerns about its use in healthcare decision-making.

However, despite these limitations, QALY remains a widely recognized and utilized tool in health economics, particularly when applied with careful consideration of its constraints. We understand that in the oncology setting in the United States, the cost-effectiveness threshold for each QALY typically ranges between $150,000 and $300,000, reflecting the country’s distributed healthcare financing systems [22]. Specifically, in cases of metastatic cancer and other diseases where the survival benefit is limited—resulting in a relatively small ICER denominator—thresholds closer to $300,000/QALY have been observed. Therefore, while it is crucial to acknowledge the limitations of QALY, particularly its potential for discrimination, it still serves as a valuable measure in evaluating the cost-effectiveness of medical interventions when used judiciously within the appropriate context. Recognizing its limitations allows for a more nuanced application, ensuring that it remains a relevant tool in health economic assessments.

Conclusion

In conclusion, our model’s estimation reveals that, NALIRIFOX is not cost-effective at a WTP threshold of $150,000 /QALY. However, pricing simulations suggest that NALIRIFOX could achieve cost-effectiveness at a WTP threshold of $150,000 per QALY if the price of irinotecan liposome were reduced to $53.24 / mg, which represents a 14.8% decrease.

Data availability

No datasets were generated or analysed during the current study.

Abbreviations

AEs:

Adverse events

CEAC:

Cost-effectiveness acceptability curve

DSA:

Deterministic sensitivity analysis

ECOG:

Eastern Cooperative Oncology Group

ICER:

Incremental cost-effectiveness ratios

IPD:

Individual patient data

mPDAC:

Metastatic pancreatic ductal adenocarcinoma

NCCN:

National Comprehensive Cancer Network

PD:

Progressed disease

PFS:

Progression-free survival

PSA:

Probabilistic sensitivity analysis

QALYs:

Quality-adjusted life years

WTP:

Willingness to pay

References

  1. Siegel RL, Miller KD, Wagle NS, Jemal A. Cancer statistics, 2023. CA Cancer J Clin. 2023;73:17–48.

    Article  PubMed  Google Scholar 

  2. Rahib L, Smith BD, Aizenberg R, Rosenzweig AB, Fleshman JM, Matrisian LM. Projecting cancer incidence and deaths to 2030: the unexpected burden of thyroid, liver, and pancreas cancers in the United States. Cancer Res. 2014;74:2913–21.

    Article  CAS  PubMed  Google Scholar 

  3. Hu ZI, O’Reilly EM. Therapeutic developments in pancreatic cancer. Nat Rev Gastroenterol Hepatol. 2023.

  4. Chiaro MD, Sugawara T, Karam SD, Messersmith WA. Advances in the management of pancreatic cancer. BMJ. 2023 [cited 2023 Dec 21];383:e073995. https://www.bmj.com/content/383/bmj-2022-073995

  5. Frampton JE, Liposomal Irinotecan. A Review in Metastatic Pancreatic Adenocarcinoma. Drugs. 2020 [cited 2023 Dec 26];80:1007–18. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7347682/

  6. Wainberg ZA, Bekaii-Saab T, Boland PM, Dayyani F, Macarulla T, Mody K, et al. First-line liposomal irinotecan with oxaliplatin, 5-fluorouracil and leucovorin (NALIRIFOX) in pancreatic ductal adenocarcinoma: a phase I/II study. Eur J Cancer. 2021;151:14–24.

    Article  CAS  PubMed  Google Scholar 

  7. Wainberg ZA, Melisi D, Macarulla T, Pazo Cid R, Chandana SR, De La Fouchardière C et al. NALIRIFOX versus nab-paclitaxel and gemcitabine in treatment-naive patients with metastatic pancreatic ductal adenocarcinoma (NAPOLI 3): a randomised, open-label, phase 3 trial. The Lancet. 2023 [cited 2023 Dec 21];402:1272–81. https://www.sciencedirect.com/science/article/pii/S0140673623013661

  8. National Comprehensive Cancer Network -. Home. NCCN. [cited 2024 Mar 27]. https://www.nccn.org

  9. Research C, for DE. and. FDA approves irinotecan liposome for first-line treatment of metastatic pancreatic adenocarcinoma. FDA. 2024 [cited 2024 Mar 27]; https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-irinotecan-liposome-first-line-treatment-metastatic-pancreatic-adenocarcinoma

  10. NALIRIFOX Improves Survival Compared with Nab-. paclitaxel Plus Gemcitabine in First-Line Treatment for Patients with Metastatic Pancreatic Ductal Adenocarcinoma. [cited 2024 Mar 27]. https://www.esmo.org/oncology-news/nalirifox-improves-survival-compared-with-nab-paclitaxel-plus-gemcitabine-in-first-line-treatment-for-patients-with-metastatic-pancreatic-ductal-adenocarcinoma

  11. Besselink MG, Wilmink JW. Treating metastatic pancreatic ductal adenocarcinoma: NALIRIFOX as new standard? Lancet. 2023;402:1217–8.

    Article  PubMed  Google Scholar 

  12. Husereau D, Drummond M, Augustovski F, de Bekker-Grob E, Briggs AH, Carswell C et al. Consolidated Health Economic Evaluation Reporting Standards 2022 (CHEERS 2022) statement: updated reporting guidance for health economic evaluations. BMJ. 2022 [cited 2023 Dec 21];376:e067975. https://www.bmj.com/content/376/bmj-2021-067975

  13. Stainthorpe A, Greenhalgh J, Bagust A, Richardson M, Boland A, Beale S et al. Paclitaxel as Albumin-Bound Nanoparticles with Gemcitabine for Untreated Metastatic Pancreatic Cancer: An Evidence Review Group Perspective of a NICE Single Technology Appraisal. PharmacoEconomics. 2018 [cited 2023 Dec 17];36:1153–63. https://doi.org/10.1007/s40273-018-0646-1

  14. Conroy T, Desseigne F, Ychou M, Bouché O, Guimbaud R, Bécouarn Y, et al. FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. N Engl J Med. 2011;364:1817–25.

    Article  CAS  PubMed  Google Scholar 

  15. Gharaibeh M, McBride A, Alberts DS, Slack M, Erstad B, Alsaid N, et al. Economic Evaluation for USA of systemic chemotherapies as First-Line treatment of metastatic pancreatic Cancer. PharmacoEconomics. 2018;36:1273–84.

    Article  PubMed  Google Scholar 

  16. Guyot P, Ades AE, Ouwens MJ, Welton NJ. Enhanced secondary analysis of survival data: reconstructing the data from published Kaplan-Meier survival curves. BMC Med Res Methodol. 2012;12:9.

    Article  PubMed  PubMed Central  Google Scholar 

  17. Centers for Medicare &. Medicaid Services | CMS. [cited 2024 Mar 27]. https://www.cms.gov/

  18. CPI Inflation Calculator. [cited 2024 Mar 27]. https://www.bls.gov/data/inflation_calculator.htm

  19. Conroy T, Pfeiffer P, Vilgrain V, Lamarca A, Seufferlein T, O’Reilly EM, et al. Pancreatic cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up. Ann Oncol. 2023;34:987–1002.

    Article  CAS  PubMed  Google Scholar 

  20. Wu B, Shi L. Cost-effectiveness of maintenance olaparib for germline BRCA-Mutated metastatic pancreatic Cancer. J Natl Compr Canc Netw. 2020;18:1528–36.

    Article  PubMed  Google Scholar 

  21. Schneider P. The QALY is ableist: on the unethical implications of health states worse than dead. Qual Life Res. 2022 [cited 2024 Aug 21];31:1545–52. https://doi.org/10.1007/s11136-021-03052-4

  22. Seabury SA, Goldman DP, Maclean JR, Penrod JR, Lakdawalla DN. Patients value metastatic cancer therapy more highly than is typically shown through traditional estimates. Health Aff (Millwood). 2012;31:691–9.

    Article  PubMed  Google Scholar 

  23. O’Neill CB, Atoria CL, O’Reilly EM, LaFemina J, Henman MC, Elkin EB. Costs and trends in pancreatic cancer treatment. Cancer. 2012 [cited 2023 Dec 17];118:5132–9. https://onlinelibrary.wiley.com/doi/abs/10.1002/cncr.27490

  24. Bao Y, Maciejewski RC, Garrido MM, Shah MA, Maciejewski PK, Prigerson HG. Chemotherapy use, end-of-Life Care, and costs of Care among patients diagnosed with Stage IV Pancreatic Cancer. J Pain Symptom Manage. 2018;55:1113–e11213.

    Article  PubMed  Google Scholar 

  25. Nafees B, Stafford M, Gavriel S, Bhalla S, Watkins J. Health state utilities for non small cell lung cancer. Health Qual Life Outcomes. 2008;6:84.

    Article  PubMed  PubMed Central  Google Scholar 

  26. de Groot S, Redekop WK, Versteegh MM, Sleijfer S, Oosterwijk E, Kiemeney La. Health-related quality of life and its determinants in patients with metastatic renal cell carcinoma. Qual Life Res. 2018;27:115–24.

    Article  PubMed  Google Scholar 

  27. Swinburn P, Lloyd A, Nathan P, Choueiri TK, Cella D, Neary MP. Elicitation of health state utilities in metastatic renal cell carcinoma. Curr Med Res Opin. 2010;26:1091–6.

    Article  PubMed  Google Scholar 

  28. Tam VC, Ko YJ, Mittmann N, Cheung MC, Kumar K, Hassan S, et al. Cost-effectiveness of systemic therapies for metastatic pancreatic cancer. Curr Oncol. 2013;20:e90–106.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Sullivan PW, Slejko JF, Sculpher MJ, Ghushchyan V. Catalogue of EQ-5D scores for the United Kingdom. Med Decis Mak. 2011;31:800–4.

    Article  Google Scholar 

  30. Ambavane A, Yang S, Atkins MB, Rao S, Shah A, Regan MM, et al. Clinical and economic outcomes of treatment sequences for intermediate- to poor-risk advanced renal cell carcinoma. Immunotherapy. 2020;12:37–51.

    Article  CAS  PubMed  Google Scholar 

  31. Baker T, Johnson H, Kotapati S, Moshyk A, Hamilton M, Kurt M, et al. Cost-utility of Nivolumab Plus Ipilimumab in First-Line Treatment of Advanced Melanoma in the United States: an analysis using long-term overall Survival Data from Checkmate 067. Pharmacoecon Open. 2022;6:697–710.

    Article  PubMed  PubMed Central  Google Scholar 

  32. 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;12:632818.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Shao T, Zhao M, Liang L, Tang W. Serplulimab Plus Chemotherapy vs Chemotherapy for treatment of US and Chinese patients with extensive-stage small-cell lung Cancer: a cost-effectiveness analysis to inform drug pricing. BioDrugs. 2023;37:421–32.

    Article  CAS  PubMed  Google Scholar 

  34. Kuznik A, Smare C, Chen C-I, Venkatachalam M, Keeping S, Atsou K, et al. Cost-effectiveness of Cemiplimab Versus Standard of Care in the United States for First-Line treatment of Advanced Non-small Cell Lung Cancer with programmed death-ligand 1 expression ≥ 50. Value Health. 2022;25:203–14.

    Article  PubMed  Google Scholar 

  35. Halloush S, Alkhatib NS, Almutairi AR, Calamia M, Halawah H, Obeng-Kusi M, et al. Economic evaluation of three BRAF + MEK inhibitors for the treatment of Advanced Unresectable Melanoma with BRAF Mutation from a US Payer Perspective. Ann Pharmacother. 2023;57:1016–24.

    Article  PubMed  Google Scholar 

  36. Courtney PT, Yip AT, Cherry DR, Salans MA, Kumar A, Murphy JD. Cost-effectiveness of Nivolumab-Ipilimumab Combination Therapy for the treatment of Advanced Non-small Cell Lung Cancer. JAMA Netw Open. 2021;4:e218787.

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

HS and HF contributed equally to this work. Concept and design: HS and MZ; Acquisition of data: YL and HF; Analysis and interpretation of data: HS, MZ, and YJ; Drafting of manuscripts, HS, YJ; Critical revision of the manuscript for important intellectual content: WT; Obtaining funding: WT.

Funding

This work was supported by the General Program of National Natural Science Foundation of China (grant no. 72174207).

Author information

Author notes

  1. Hanqiao Shao and Hongshu Fang contributed equally to this work.

Authors and Affiliations

  1. School of International Pharmaceutical Business, China Pharmaceutical University, Nanjing, Jiangsu, China

    Hanqiao Shao, Hongshu Fang, Yuan Li, Mingye Zhao & Wenxi Tang

  2. Center for Pharmacoeconomics and Outcomes Research, Department of Public Affairs Management, School of International Pharmaceutical Business, China Pharmaceutical University, Nanjing, Jiangsu, China

    Hanqiao Shao, Hongshu Fang, Yuan Li, Mingye Zhao & Wenxi Tang

  3. Nanjing Hospital of Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing, China

    Yunlin Jiang

  4. Nanjing University of Chinese Medicine, Nanjing, China

    Yunlin Jiang

Authors
  1. Hanqiao Shao
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Hongshu Fang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yuan Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yunlin Jiang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Mingye Zhao
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Wenxi Tang
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Concept and design: HS and MZ; Acquisition of data: YL and HF; Analysis and interpretation of data: HS, MZ, and YJ; Drafting of manuscripts, HS, YJ; Critical revision of the manuscript for important intellectual content: WT; Obtaining funding: WT. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Wenxi Tang.

Ethics declarations

Ethics approval and consent to participate

Not applicable, this study does not involve human participants or animal subjects.

Consent for publication

All authors agreed to the publication of this manuscript.

Competing interests

The authors declare no competing interests.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary Material 1

Supplementary Material 2

Rights and permissions

Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc-nd/4.0/.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Shao, H., Fang, H., Li, Y. et al. Economic evaluation of NALIRIFOX vs. nab-paclitaxel and gemcitabine regimens for first-line treatment of metastatic pancreatic ductal adenocarcinoma from U.S. perspective. Cost Eff Resour Alloc 22, 70 (2024). https://doi.org/10.1186/s12962-024-00578-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1186/s12962-024-00578-5

Keywords

Cost Effectiveness and Resource Allocation

ISSN: 1478-7547

Contact us