Cost effectiveness of pembrolizumab plus lenvatinib compared with chemotherapy for treating previously treated advanced endometrial cancer in Sweden

Abstract

Objective

Pembrolizumab plus lenvatinib was recently approved for the treatment of advanced or recurrent endometrial carcinoma in women with disease progression on or following prior treatment with a platinum‑containing therapy in any setting, and who are not candidates for curative surgery or radiation (KEYNOTE-775/Study-309; NCT03517449). The objective was to assess the cost effectiveness of pembrolizumab plus lenvatinib compared with chemotherapy from a Swedish healthcare perspective.

Materials and methods

A lifetime partitioned-survival model with three health states (progression free, progressed disease, death) was constructed. Chemotherapy was represented by paclitaxel or doxorubicin. Overall survival, progression-free survival, time on treatment, and utility data were obtained from KEYNOTE-775 (database lock: March 1, 2022). Costs (in 2020 Swedish Krona [SEK]) included drug acquisition and administration, health state, end of life, adverse event management, subsequent treatment, and societal (scenario analysis). Outcomes were calculated as quality-adjusted life-years (QALY) and life-years. Model results were presented as incremental cost-effectiveness ratios for all-comers, patients with proficient mismatch repair tumors, and deficient mismatch repair tumors. Deterministic and probabilistic sensitivity analyses were conducted.

Results

Pembrolizumab plus lenvatinib is a cost-effective treatment when compared with chemotherapy, with estimated deterministic and probabilistic incremental cost-effectiveness ratios of SEK 795,712 and 819,757 per QALY gained. Pembrolizumab plus lenvatinib was associated with a large incremental QALY and life-year gain per person versus chemotherapy over the model time horizon (1.49 and 1.76).

Limitations

Time-to-event data were incomplete and semiparametric and parametric curves were utilized for lifetime extrapolation. Willingness-to-pay thresholds, costs, and utility weights vary by country, which would vary the treatment’s cost effectiveness in different countries.

Conclusions

This partitioned survival analysis suggests that pembrolizumab plus lenvatinib is cost effective compared with chemotherapy in Sweden for women with advanced or recurrent endometrial carcinoma following previous systemic therapy. Results were robust to mismatch repair status and to changes in parameters/assumptions.

Keywords:

• Cost effectiveness
• pembrolizumab
• lenvatinib
• chemotherapy
• advanced endometrial cancer
• decision analytic model
• Sweden

JEL Classification Codes:

• D60
• D6
• D
• I10
• I1
• I

Introduction

Endometrial cancer is the sixth most common cancer in women globally¹. In Sweden, around 1,400 patients had endometrial cancer in 2020². For patients with advanced endometrial cancer, median survival from initiation of second-line treatment was 10.3 months in a real-world study³. There are limited treatment options for women with advanced stages of endometrial cancer following previous systemic therapy. Prior to the approval of pembrolizumab plus lenvatinib, European guidelines included paclitaxel, pegylated liposomal doxorubicin, and topotecan⁴. Swedish treatment guidelines recommended a combination of paclitaxel and carboplatin as first-line treatment, and liposomal doxorubicin as second-line treatment².

Pembrolizumab is a monoclonal antibody with high specificity of binding to the programmed cell death-protein 1 (PD-1)⁵. Lenvatinib is a multiple kinase inhibitor targeted against the vascular endothelial growth factor (VEGF) receptor kinases⁶. The clinical efficacy of pembrolizumab plus lenvatinib in previously treated advanced endometrial cancer was established in Study 309/KEYNOTE-775 (NCT03517449), a Phase III trial that included mismatch repair status as a stratification factor^7,8. Study 309/KEYNOTE-775 demonstrated statistically significant and clinically meaningful improvements in progression-free survival, overall survival, and objective response rate for pembrolizumab plus lenvatinib compared with paclitaxel or doxorubicin in the overall population, in patients with mismatch repair–proficient disease, and the population with mismatch repair-deficient disease⁷.

Cost-effectiveness analyses play an important role in the decision to reimburse healthcare providers for pharmaceuticals worldwide. The objective of this analysis was to assess the cost effectiveness of pembrolizumab plus lenvatinib compared with the physician’s choice of chemotherapy in women with advanced or recurrent endometrial carcinoma who had disease progression on or following prior treatment with a platinum‑containing therapy in any setting, and who are not candidates for curative surgery or radiation from the Swedish healthcare payer perspective.

Materials and methods

This study was based on previously collected, anonymized clinical trial data provided by the study sponsor who received ethical approval to conduct the study; therefore, the authors were not required to obtain additional ethical approval nor was consent from participants required.

Patient population

The target population was adult (aged ≥18 years) women with advanced or recurrent endometrial carcinoma with disease progression on or following prior treatment with a platinum‑containing therapy in any setting, and who are not candidates for curative surgery or radiation consistent with the overall population of KEYNOTE-775. Mismatch repair subpopulation analysis was also conducted, including patients with proficient and deficient mismatch repair tumors.

Perspective

The analysis was conducted from a Swedish healthcare payer perspective using a willingness-to-pay threshold of 1,000,000 Swedish Krona (SEK) per quality-adjusted life-year (QALY) over a lifetime horizon (40 years)⁹. Patients with deficient mismatch repair endometrial carcinoma show a robust response to treatment and there may be a subset of patients with durable long-term survival. Therefore, a lifetime time horizon was chosen following Swedish and other guidelines^9,10. A societal perspective considering indirect costs was explored in a scenario analysis, as requested by some health technology assessment bodies, including the Tandvårds- och läkemedelsförmånsverket (TLV). Costs and benefits were discounted at an annual rate of 3.0%¹¹.

Intervention and comparators

• Pembrolizumab 200 mg (administered via intravenous [IV] infusion every 21 d) for up to 35 cycles of therapy, in combination with lenvatinib 20 mg (oral) once daily for each 21 d cycle;

• Physician’s choice of chemotherapy (paclitaxel 80 mg/m² administered weekly via IV infusion for 3 weeks out of four until disease progression or doxorubicin 60 mg/m² administered every 21 d via IV infusion, until a lifetime cumulative dose of 500 mg/m²). Survival data are not available for liposomal doxorubicin. Thus, chemotherapy efficacy is based on KEYNOTE-775 and the costs are for standard chemotherapy, which is a conservative assumption because liposomal doxorubicin is substantially more expensive.

Model overview

A partitioned-survival model comprising three health states (progression free, progressed disease, death) was constructed in Microsoft Excel. Partitioned-survival models are commonly used to assess the cost effectiveness of new treatments in advanced or metastatic cancer using time-to-event data from oncology clinical trials¹². Patients entered the model in the progression-free health state and could remain progression free, transition to progressed disease, or die in each cycle. Patients who transitioned to progressed disease could then remain in this health state or die. Death is an absorbing health state where patients remained for the model time horizon.

The proportion of patients in the progression-free health state was defined as the area under the progression-free survival curve. The proportion of patients in the death health state was defined as one minus the area under the overall survival curve. The proportion of patients with progressed disease was estimated as the difference between overall survival and progression-free survival curves.

Life expectancy data from Swedish life tables were included to account for age-specific all-cause mortality. A 1-week cycle was used in the model to capture incremental costs and benefits, ensuring treatment regimens were costed accurately.

Model inputs

A summary of all inputs and associated distribution data included in the analysis is presented in Table 1.

Table 1. Model inputs.

Input	Mean value	Distribution	Source
Model settings
Time horizon (years)	40	N/A	Tandvårds- och läkemedelsförmånsverket. General guidelines for economic evaluations^9
Cycle length (weeks)	1	N/A
Discount rate (costs, outcomes), %	3	N/A
Baseline characteristics
Age (years)	63.50	Normal	KEYNOTE-775^7
Average patient weight (kg)	70.50	Log-normal
Average patient BSA (m^2)	1.77	Normal
Overall survival
PEM + LEN	KM (Wk 26)+log-logistic models	MV normal	KEYNOTE-775^13
Chemotherapy	Treatment switch adjustment HR, 0.60	Log-normal	KEYNOTE-775^13
Progression-free survival
PEM + LEN	Independent KM (Wk10)+ generalized gamma models	MV normal	KEYNOTE-775^13
Chemotherapy		MV normal	KEYNOTE-775^13
Costs (SEK)
Cost of PEM 100 mg	33,519.50	Gamma	Tandvårds- och läkemedelsförmånsverket drug price index^14
Cost of LEN 4 mg	16,180.61	Gamma
Cost of LEN 10 mg	16,180.61	Gamma
Cost of PAC 30 mg	146.25	Gamma
Cost of PAC 100 mg	386.93	Gamma
Cost of DOX 50 mg	203.50	Gamma
Cost of DOX 10 mg	67.50	Gamma
Cost of subsequent treatment upon treatment discontinuation (PEM + LEN)	66,033.88	Gamma
Cost of subsequent treatment upon treatment discontinuation (chemotherapy)	34,267.92	Gamma
Cost of IV administration	5,878.00	Gamma	Southwest region price list^15
Resource use costs/cycle (progression free)	1,121.84	Gamma	Southwest region price list^15
Resource use costs/cycle (progressed disease)	223.89	Gamma
AEs/cycle (pembrolizumab plus)	317.01	Normal	Southwest region price list^15
AEs/cycle (chemotherapy)	1,094.01	Normal
End-of-life cost upon death^a	12,165.86	Gamma	Opdivo and Yervoy submission (Tandvårds- och läkemedelsförmånsverket)^11
Utility
≥360 d	0.869	MV normal	Calculated from KEYNOTE-775^13
270–359 d	0.861	MV normal
180–269 d	0.830	MV normal
90–179 d	0.822	MV normal
30–89 d	0.772	MV normal
<30 d	0.675	MV normal

Abbreviations. AE, adverse event; BSA, body surface area; DOX, doxorubicin; HR, hazard ratio; IV, intravenous; KM, Kaplan–Meier; LEN, lenvatinib; MV, multivariate; N/A, not applicable; PAC, paclitaxel; PEM, pembrolizumab; SEK, Swedish Krona; Wk, Week.

^a The end-of life cost upon death was calculated as follows: the reported 96,000 SEK¹¹ was assumed to be the last 8 weeks of life; this value was adjusted for inflation and divided by 8 to obtain the cost in the final week of life.

Clinical inputs

Overall survival, progression-free survival, time on treatment, adverse events, and utility data for pembrolizumab plus lenvatinib and chemotherapy were sourced from the KEYNOTE-775 final analysis (database lock: March 1, 2022)¹³. Observed overall survival and progression-free survival Kaplan–Meier data were only available through trial follow-up, so were extrapolated beyond the trial follow-up period using parametric survival models^16,17.

Modelled and observed overall survival and progression-free survival for pembrolizumab plus lenvatinib and chemotherapy are presented alongside observed longer-term pembrolizumab plus lenvatinib KEYNOTE-146 (NCT02501096) overall survival data in Figure 1¹⁸.

Figure 1. Estimation of overall survival (A) and progression-free survival (B). Abbreviations. KM, Kaplan–Meier; LEN, lenvatinib; OS, overall survival; PEM, pembrolizumab; PFS, progression-free survival.

Overall survival

Both one-piece survival models and two-piece Kaplan–Meier (Week 26) plus survival model extrapolations were considered. The goodness-of-fit of each one-piece and two-piece survival model to the observed data was assessed visually and objectively using the Akaike information criterion and Bayesian information criterion statistics^16,17. Final selections were validated by clinicians.

The observed hazard associated with pembrolizumab plus lenvatinib was assessed and showed a change at approximately 26 weeks (i.e. there was a different slope before and after 26 weeks). Two-piece extrapolations fit the observed hazard data better than one-piece extrapolations and provided more plausible long-term extrapolations. Following the 26-week cut point, the log-logistic model provided the most plausible fit to the observed hazard of death and offered a plausible long-term extrapolation supported by external data (KEYNOTE-146). A Kaplan–Meier (Week 26) plus log-logistic extrapolation was selected for pembrolizumab plus lenvatinib.

For chemotherapy, treatment-switching methods were used to remove subsequent PD-1/programmed death-ligand 1 (PD-L1) and VEGF/VEGF receptor treatments not expected in clinical practice¹⁹. An adjusted hazard ratio using the two-stage without recensoring methodology was then applied to the pembrolizumab plus lenvatinib extrapolation to generate a chemotherapy extrapolation in the overall population and the proficient mismatch repair population. An unadjusted hazard ratio was used within the deficient mismatch repair subpopulation analysis.

The selected overall survival curves are presented in Figure 1. Alternative survival models were tested in scenario analyses. Visual and statistical fits are presented in the Supplementary material (Tables S1 and S3; Figures S1, S2, S5, S6, S9, and S10).

Progression-free survival

Progression-free survival Kaplan–Meier data for pembrolizumab plus lenvatinib and chemotherapy were also extrapolated using one- and two-piece methods. Week 10 was included as a cut-off point for progression-free survival, corresponding to the first scheduled radiologic assessment of progression in KEYNOTE-775.

Each model was assessed visually and objectively, and final selections were validated by clinicians. Two-piece extrapolations fit the observed hazard data better, provided more plausible long-term extrapolations, and maintained consistency with overall survival modeling. All two-piece models fit the data well and the generalized gamma extrapolation was selected for the base-case analysis. Selected progression-free survival curves are presented in Figure 1. Alternative survival models were tested in scenario analyses. Visual and statistical fits are presented in the Supplementary material (Tables S1, S3, S4; Figures S3, S4, S7, S8, S11, and S12).

Time on treatment

Time-on-treatment data were used to establish the proportion of patients on treatment in each model cycle, used to calculate the overall drug, administration, and adverse event costs.

Time on treatment was modeled separately for pembrolizumab, lenvatinib, and chemotherapy. Kaplan–Meier data were extrapolated using one-piece survival models. There were few differences between short- and long-term outcomes between each extrapolation, so for pembrolizumab, lenvatinib, and chemotherapy, the generalized gamma extrapolation was used as it presented a superior statistical fit (see Supplementary material Table S2).

Pembrolizumab time-on-treatment was set to 0% from 24 months, consistent with the maximum treatment duration implemented in KEYNOTE-775 and clinical practice (35 cycles). Doxorubicin was set to a maximum cumulative dose of 500 mg/m² consistent with KEYNOTE-775⁷.

Health-related quality of life

Utility values were derived from patient-reported EuroQol five-dimension, five-level (EQ-5D-5L) scores collected in KEYNOTE-775²⁰. A time-to-death approach was used in the base-case analysis (Table 1). This approach removes the dependence on subjective clinical assessments of progression status. Utility values were applied consistently across treatment arms and were age adjusted to account for the natural decline in quality of life. Subpopulation-specific utility values were included (see Supplementary Table S5).

Cost inputs

All costs were expressed in SEK and were from the 2020 cost year.

Drug costs were obtained from the Swedish Dental and Pharmaceutical Benefits Agency drug–cost database and the Apoteket (Table 1)^14,21. Administration and disease management costs were sourced from the Southern Healthcare Region¹⁵. Healthcare resource use for the progression-free and progressed disease health state were sourced from a previous ovarian cancer analysis²². End-of-life costs were sourced from a TLV appraisal in renal cell carcinoma and applied at the point of death^11,23.

The overall cost of the chemotherapy arm in the model was weighted using the proportion of patients who received paclitaxel and doxorubicin, as observed in KEYNOTE-775²⁴.

Adverse events

Treatment-related Grade 3+ adverse events with an incidence of at least 3% were included in the model. Adverse event costs and disutilities were applied per cycle while on treatment.

Subsequent treatment

The proportion of patients that received subsequent therapy, the share and duration of treatments after receiving pembrolizumab plus lenvatinib and chemotherapy, was informed by KEYNOTE-775²⁴. In addition, routine home care was assumed to be provided as a palliative care option alongside or in place of subsequent therapy. Subsequent treatment costs were applied as a one-off cost on treatment discontinuation for those in the cohort still alive.

Societal perspective

The human capital method was explored in scenario analysis to capture indirect costs incurred from production losses from patients treated with pembrolizumab plus lenvatinib and chemotherapy²⁵.

It was assumed that 10% and 50% of work hours were lost from patients while in the progression-free and progressed disease states, respectively. The societal cost per week was calculated as the product of working hours and average wage per hour. Complete productivity is lost upon death. We assume that patients retire at 67 years. Consistent with a prior approach, the number of productive years remaining for the proportion of patients dying in each cycle was calculated²⁶. These productive years were multiplied by the expected wage for the cohort and the proportion of patients in full-time work, in order to calculate the expected productivity loss of patients dying before retirement.

Outcomes

Costs and utilities were calculated over the time horizon to estimate the total costs, life-years, and QALYs for pembrolizumab plus lenvatinib and chemotherapy. Incremental costs and QALYs were then used to estimate the incremental cost-effectiveness ratio.

Deterministic and probabilistic sensitivity analyses were carried out to test the robustness of model assumptions. The probabilistic-sensitivity analysis included 1,000 iterations. A range of scenario analyses were carried out to test model assumptions. The distributions assigned to each model input are described in Table 1 for each variable included within the sensitivity analyses.

Results

Base case results

Base case cost-effectiveness results are presented in Table 2. A cohort treated with pembrolizumab plus lenvatinib and chemotherapy would gain 3.46 and 1.71 life-years, and 2.93 and 1.44 QALYs, respectively. Costs associated with pembrolizumab plus lenvatinib are SEK 1,484,976 compared with SEK 297,904 for chemotherapy.

Table 2. Cost effectiveness of pembrolizumab plus lenvatinib compared with chemotherapy.

	Total discounted costs (SEK)	Total discounted life-years	Total discounted QALYs	Incremental			ICER (SEK per QALY)
				Discounted Costs (SEK)	Discounted life-years	Discounted QALYs
All-comers
Chemotherapy	297,904	1.70	1.44	–	–	–	–
PEM + LEN	1,484,976	3.46	2.93	1,187,073	1.76	1.49	795,712
Proficient mismatch repair
Chemotherapy	295,258	1.77	1.50	–	–	–	–
PEM + LEN	1,486,968	3.24	2.75	1,191,710	1.46	1.24	958,306

Abbreviations. ICER, incremental cost-effectiveness ratio; LEN, lenvatinib; PEM, pembrolizumab; QALY, quality-adjusted life-year; SEK, Swedish Krona.

Pembrolizumab plus lenvatinib was associated with an overall incremental cost-effectiveness ratio (ICER) of SEK 795,712 per QALY gained versus chemotherapy. The ICER for the proficient mismatch repair subpopulation is SEK 958,306 per QALY. The results for the deficient mismatch repair subpopulation are presented in the Supplementary material (Table S6).

Probabilistic sensitivity analysis

The probabilistic sensitivity analysis had an ICER of SEK 819,757 per QALY with a 95% chance of pembrolizumab with lenvatinib being cost effective compared with chemotherapy at a willingness-to-pay threshold of SEK 1,000,000 per QALY (see Supplementary Figure S13).

One-way sensitivity analysis and scenario analysis

Deterministic results were tested in one-way sensitivity analysis and scenario analyses, and were found to be robust to all changes explored (Figure 2). In the one-way sensitivity analysis, the model inputs or assumptions with the largest impact on the ICER were associated with overall survival and time on treatment.

Figure 2. Deterministic sensitivity analysis tornado plot all-comers. Increasing the hazard ratio decreased the ICER as the OS hazard ratio was entered as 1/0.06; therefore, the resulting lower bound value was greater than the upper bound value in some cases. Abbreviations. ICER, incremental cost-effectiveness ratio; LEN, lenvatinib; MRU, medical resource utilization; OS, overall survival; PEM, pembrolizumab; PFS, progression-free survival; SEK, Swedish Krona; SoC, standard of care.

All scenario analyses for pembrolizumab plus lenvatinib in the all-comers population reported incremental cost-effectiveness ratios below SEK 1,000,000 per QALY (Table 3).

Table 3. Scenario results.

Parameter	Base case setting	Scenario setting	PEM + LEN versus chemotherapy ICER (SEK)
Base case			795,712
Discount rate (costs and utilities), %	3.0	0.0	629,817
		5.0	905,944
Time horizon, years	40	30	804,026
Subsequent treatment, %	28 for PEM + LEN, 48 for chemotherapy	100	804,155
		0	801,086
Perspective	Healthcare payer	Societal	732,130
Utility	Time to death approach	Health state approach	829,651
	Sweden tariff	UK tariff	923,210
	Age-adjustment included	Age-adjustment excluded	776,341
Overall survival	Treatment switch adjustment	Separate Kaplan–Meier + log-logistic models	933,980
Progression-free survival	Separate Kaplan–Meier (Wk 10) +log-logistic models	Separate Kaplan–Meier (Wk 10) +log-normal models	791,341
		Separate Kaplan–Meier (Wk 37) +log-logistic models	808,011
		Separate one-piece log-logistic models	800,017
Time on treatment	Separate one-piece generalized gamma models	Weibull	905,130
		Progression-free survival as proxy	997,266
		Capped by progression-free survival	901,023

Abbreviations. ICER, incremental cost-effectiveness ratio; LEN, lenvatinib; PEM, pembrolizumab; SEK, Swedish Krona; UK, United Kingdom; Wk, Week.

Discussion

To our knowledge, this is the first study to evaluate the cost effectiveness of pembrolizumab in combination with lenvatinib in Sweden for women with advanced or recurrent endometrial carcinoma following previous systemic therapy. From the Swedish healthcare payer perspective, pembrolizumab plus lenvatinib is a cost-effective treatment option compared with chemotherapy within the defined population. Sensitivity and scenario analyses demonstrate that these results are robust to changes in the model parameters.

This analysis quantifies the incremental costs and health gains with pembrolizumab plus lenvatinib in the overall population and mismatch repair subgroups. Pembrolizumab plus lenvatinib is associated with improvements in QALYs when considering quality of life along with improvements in length of life, and is considered a cost-effective treatment option below the Swedish threshold. The societal perspective reduces the deterministic ICER compared with the base case and reinforces the improved survival prospects of patients treated with pembrolizumab plus lenvatinib compared with chemotherapy.

Treatment-switching methods adjust for differing subsequent treatments administered in a clinical trial setting and that are available in clinical practice. This approach accounted for the lack of PD-1/PD-L1 and VEGF/VEGF receptor treatments available in clinical practice during later-line treatment. While treatment-switching methods may generate survival extrapolations that are more representative to real-world chemotherapy treatment, they use an adjusted hazard ratio to create a curve for chemotherapy overall survival. Deficient mismatch repair subpopulation results can be considered conservative because an unadjusted hazard ratio is used in this subpopulation. In a scenario analysis, pembrolizumab plus lenvatinib remains cost effective in the all-comer population without adjustment for subsequent PD-1/PD-L1 and VEGF/VEGF receptor treatments.

This analysis has several strengths. The model structure is consistent with other cost-effectiveness analyses in advanced or metastatic cancer and was constructed according to general guidelines for economic evaluations¹⁶. The analysis utilized time-to-event data and safety data from KEYNOTE-775, the only Phase III clinical trial with data available in this patient population. Earlier Phase I/II trials investigated the efficacy of immunotherapies in the deficient mismatch repair population only. Data for these treatments are not available in the all-comers population and, as such, have been excluded in this analysis. The KEYNOTE-775 trial had a representative patient sample from multiple countries and used a physician’s choice chemotherapy treatment reflecting current clinical practice (doxorubicin and paclitaxel). Therefore, survival and health outcomes derived from the trial are generally representative of European countries for women who would be similar to those enrolled in the trial. Furthermore, the total life-years with chemotherapy are generally consistent with another publication of cost effectiveness in women with unresectable or metastatic endometrial cancer^27,28.

This analysis also has a number of limitations. Time-to-event data were incomplete and both semi-parametric and parametric curves were utilized for lifetime extrapolation. However, pembrolizumab plus lenvatinib survival extrapolations are consistent with long-term data from KEYNOTE-146²⁹. Extrapolations beyond the observed KEYNOTE-775 data were also reviewed and validated by clinical experts. Where inputs were unavailable for advanced endometrial cancer, ovarian cancer-based and renal cell carcinoma-based inputs were used. Willingness-to-pay thresholds, costs, and utility weights vary by country, which would vary the cost effectiveness of the treatment in different markets.

Costs and specifically drug acquisition costs, utility weights, life-expectancy, and cost-effectiveness thresholds vary across different countries. This Swedish analysis would need to be adapted to assess the cost effectiveness of the combination for an individual country. Further, the patient population in the real world is likely to include patients with worse performance status, different histology, etc., and the cost effectiveness in these patient populations could vary depending upon the relative survival of patients in these groups.

Conclusions

From a Swedish healthcare payer perspective, pembrolizumab plus lenvatinib is a cost-effective treatment option compared with physician’s choice of chemotherapy treatment for adult women with advanced or recurrent endometrial carcinoma with disease progression on or following prior treatment. Given the clinically meaningful and statistically significant improvement in efficacy and the economic value as assessed through the cost-effectiveness analysis, pembrolizumab plus lenvatinib should be considered in this practice setting.

Transparency

Author contributions

Conceptualization: LR, AM, NU, VSP

Formal analysis: LR, AM, KY, NU, RX, RM

Investigation: NU, VSP, RX, AG, CL, RM

Methodology: LR, AM

Validation: RO, LD.

All authors were involved in drafting of the paper and/or revising it critically for intellectual content, as well as approving the final version to be published. All authors agree to be accountable for all aspects of the work.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Previous presentations

A cost-effectiveness analysis of this treatment combination has previously been presented at the 2021 International Gynecologic Cancer Society (IGCS) Annual Global Meeting; August 30–September 2, 2021.

Acknowledgements

Editorial assistance was provided by Russell Craddock, of Parexel, and was funded by MSD.

Declaration of financial/other relationships

LR and AM are employees of Lumanity and received a consultancy fee to conduct this analysis on behalf of MSD.

AG is an employee/consultant of Quantify Research and received a consultancy fee to conduct this analysis on behalf of MSD.

KY, NU, VSP, RX, and RO are employees of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA, and may own stocks or shares in, Merck & Co., Inc., Rahway, NJ, USA.

CL and RM are employees of MSD and may own stocks or shares in Merck & Co., Inc., Rahway, NJ, USA.

LD reports research funding (to institution) for investigator-initiated trials from Merck; clinical trial grants (to institution) from AbbVie/(GOG 3005), Acrivon, Aduro BioTech, Advaxis, Alkermes, Blueprint, Constellation, Eisai, Genentech/Roche, GlaxoSmithKline/Novartis, Immunogen, Inovio, Iovance, Karyopharm, KSQ Therapeutics, Lycera, Merck, Morab, MorphoTek, Naveris, Nurix, OncoQuest, Pfizer, Syndax, Tesaro, Zentalis; royalties or licenses from American Society of Clinical Oncology (as an Editor of American Society of Clinical Oncology Connection), UpToDate, and Wiley; consulting fees from Aadi Bioscience, Merck, and Regeneron; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Advance Medical, CEA Group, and Clinical Care Options; participation in a Data Safety Monitoring Board (to institution) or advisory board for Innovio and Aegenus; a leadership or fiduciary role as Secretary Treasurer for SGO (unpaid); and a position on the British Journal of Obstetrics and Gynaecology editorial board.

Data availability statement

The corresponding author has full access to all the data in the study. MSD is committed to providing qualified scientific researchers access to anonymized data and clinical study reports from the company’s clinical trials for the purpose of conducting legitimate scientific research. MSD is also obligated to protect the rights and privacy of trial participants and, as such, has a procedure in place for evaluating and fulfilling requests for sharing company clinical trial data with qualified external scientific researchers. The MSD data-sharing website (available at: http://engagezone.msd.com/ds_documentation.php) outlines the process and requirements for submitting a data request.

Additional information

Funding

This work was supported by Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA (MSD).