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

Transparency

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.

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.

Acknowledgements

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

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.

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.

Additional information

Funding

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