Research ArticleOpen Access cc icon

Cost–effectiveness of pembrolizumab plus chemotherapy as first-line treatment in PD-L1-positive metastatic triple-negative breast cancer

Min Huang

Peter Fasching

Amin Haiderali

Wilbur Pan

Emma Gray

Zheng-Yi Zhou

Peter Hu

Mitashri Chaudhuri

Celine Le Bailly De Tilleghem

Nicolas Cappoen

Joyce O’Shaughnessy

Min Huang

*Author for correspondence:

E-mail Address: min_huang@merck.com

Merck & Co., Inc., Kenilworth, NJ, USA

Search for more papers by this author

Peter Fasching

Comprehensive Cancer Center Erlangen-EMN, University Hospital Erlangen, Department of Gynecology & Obstetrics, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany

Search for more papers by this author

Amin Haiderali

https://orcid.org/0000-0002-6858-1564

Merck & Co., Inc., Kenilworth, NJ, USA

Search for more papers by this author

Wilbur Pan

Merck & Co., Inc., Kenilworth, NJ, USA

Search for more papers by this author

Emma Gray

Analysis Group Inc., London, UK

Search for more papers by this author

Zheng-Yi Zhou

Analysis Group Inc., London, UK

Search for more papers by this author

Peter Hu

Merck & Co., Inc., Kenilworth, NJ, USA

Search for more papers by this author

Mitashri Chaudhuri

Complete HEOR Solutions (CHEORS), North Wales, PA, USA

Search for more papers by this author

Celine Le Bailly De Tilleghem

MSD, HTA Statistics Europe, Brussels, Belgium

Search for more papers by this author

Nicolas Cappoen

MSD, HTA Statistics Europe, Brussels, Belgium

Search for more papers by this author

Joyce O’Shaughnessy

Baylor University Medical Center, Texas Oncology & US Oncology, Dallas, TX, USA

Search for more papers by this author

Published Online:7 Jul 2022https://doi.org/10.2217/imt-2022-0082

View article

Abstract

Objective: This study evaluated the cost–effectiveness of pembrolizumab/chemotherapy combinations for previously untreated metastatic triple-negative breast cancer patients in the USA with PD-L1 combined positive score ≥10. Methods: A partitioned-survival model was developed to project health outcomes and direct medical costs over a 20-year time horizon. Efficacy and safety data were from randomized clinical trials. Comparative effectiveness of indirect comparators was assessed using network meta-analyses. A series of sensitivity analyses were performed to test the robustness of the results. Results: Pembrolizumab/chemotherapy resulted in total quality-adjusted life-year (QALY) gains of 0.70 years and incremental cost–effectiveness ratio of US$182,732/QALY compared with chemotherapy alone. The incremental cost–effectiveness ratio for pembrolizumab/nab-paclitaxel versus atezolizumab/nab-paclitaxel was US$44,157/QALY. Sensitivity analyses showed the results were robust over plausible values of model inputs. Conclusion: Pembrolizumab/chemotherapy is cost effective compared with chemotherapy as well as atezolizumab/nab-paclitaxel as first-line treatment for PD-L1-positive metastatic triple-negative breast cancer from a US payer perspective.

Keywords:

Papers of special note have been highlighted as: • of interest; •• of considerable interest

References

1. Siegel RL, Miller KD, Fuchs HE, Jemal A. Cancer statistics, 2021. CA Cancer J. Clin. 71(1), 7–33 (2021).
MedlineGoogle Scholar
2. Acheampong T, Kehm RD, Terry MB, Argov EL, Tehranifar P. Incidence trends of breast cancer molecular subtypes by age and race/ethnicity in the US from 2010 to 2016. JAMA Netw. Open 3(8), e2013226 (2020).
MedlineGoogle Scholar
3. Ensenyat-Mendez M, Llinàs-Arias P, Orozco JIJ et al. Current triple-negative breast cancer subtypes: dissecting the most aggressive form of breast cancer. Front. Oncol. 11, 681476 (2021).
MedlineGoogle Scholar
4. Wahba HA, El-Hadaad HA. Current approaches in treatment of triple-negative breast cancer. Cancer Biol. Med. 12(2), 106–116 (2015).
Medline CASGoogle Scholar
5. Martínez-Sáez O, Prat A. Current and future management of HER2-positive metastatic breast cancer. JCO Oncol. Pract. 17(10), 594–604 (2021).
MedlineGoogle Scholar
6. Dent R, Trudeau M, Pritchard KI et al. Triple-negative breast cancer: clinical features and patterns of recurrence. Clin. Cancer Res. 13(15 Pt 1), 4429–4434 (2007).
MedlineGoogle Scholar
7. Aly A, Shah R, Hill K, Botteman MF. Overall survival costs and healthcare resource use by number of regimens received in elderly patients with newly diagnosed metastatic triple-negative breast cancer. Future Oncol. 15(9), 1007–1020 (2019).
CASGoogle Scholar
8. Adel NG. Current treatment landscape and emerging therapies for metastatic triple-negative breast cancer. Am. J. Manag. Care 27(5), S87–S96 (2021).
MedlineGoogle Scholar
9. Furlanetto J, Loibl S. Optimal systemic treatment for early triple-negative breast cancer. Breast Care (Basel) 15(3), 217–226 (2020).
MedlineGoogle Scholar
10. Kassam F, Enright K, Dent R et al. Survival outcomes for patients with metastatic triple-negative breast cancer: implications for clinical practice and trial design. Clin. Breast Cancer 9(1), 29–33 (2009).
MedlineGoogle Scholar
11. Heimes AS, Schmidt M. Immuno-oncology in triple-negative breast cancer. J. Cancer Metastasis Treat. 7, 9 (2021).
Google Scholar
12. Emens LA, Middleton G. The interplay of immunotherapy and chemotherapy: harnessing potential synergies. Cancer Immunol. Res. 3(5), 436–443 (2015).
Medline CASGoogle Scholar
13. US Food and Drug Administration. FDA approves atezolizumab for PD-L1 positive unresectable locally advanced or metastatic triple-negative breast cancer (18 March 2019). www.fda.gov/drugs/drug-approvals-and-databases/fda-approves-atezolizumab-PD-L1-positive-unresectable-locally-advanced-or-metastatic-triple-negative
Google Scholar
14. ESMO Oncology News. EMA recommends extension of indications for atezolizumab (28 June 2019). www.esmo.org/oncology-news/EMA-Recommends-Extension-of-Indications-for-Atezolizumab
Google Scholar
15. Schmid P, Adams S, Rugo HS et al. Atezolizumab and nab-paclitaxel in advanced triple-negative breast cancer. N. Engl. J. Med. 379(22), 2108–2121 (2018). • Data from the IMpassion130 trial were used in previous cost–effectiveness analyses of atezolizumab plus nab-paclitaxel in PD-L1-positive triple-negative breast cancer.
Medline CASGoogle Scholar
16. Schmid P, Rugo HS, Adams S et al. Atezolizumab plus nab-paclitaxel as first-line treatment for unresectable, locally advanced or metastatic triple-negative breast cancer (IMpassion130): updated efficacy results from a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 21(1), 44–59 (2020).
Medline CASGoogle Scholar
17. Miles D, Gligorov J, André F et al. Primary results from IMpassion131, a double-blind, placebo-controlled, randomised phase III trial of first-line paclitaxel with or without atezolizumab for unresectable locally advanced/metastatic triple-negative breast cancer. Ann. Oncol. 32(8), 994–1004 (2021).
Medline CASGoogle Scholar
18. US Food and Drug Administration. FDA grants accelerated approval to pembrolizumab for locally recurrent unresectable or metastatic triple negative breast cancer (13 November 2020). www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-pembrolizumab-locally-recurrent-unresectable-or-metastatic-triple.
Google Scholar
19. US Food and Drug Administration. FDA approves pembrolizumab for high-risk early-stage triple-negative breast cancer (7 July 2021). www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-pembrolizumab-high-risk-early-stage-triple-negative-breast-cancer.
Google Scholar
20. Cortes J, Cescon DW, Rugo HS et al. Pembrolizumab plus chemotherapy versus placebo plus chemotherapy for previously untreated locally recurrent inoperable or metastatic triple-negative breast cancer (KEYNOTE-355): a randomised, placebo-controlled, double-blind, phase 3 clinical trial. Lancet 396(10265), 1817–1828 (2020). •• Primary clinical publication of the KEYNOTE-355 trial (NCT02819518), which was the main data source of this study.
MedlineGoogle Scholar
21. Rugo HS, Cortés J, Cescon DW et al. KEYNOTE-355: final results from a randomized double-blind phase III study of first-line pembrolizumab + chemotherapy vs. placebo + chemotherapy for metastatic TNBC. Ann. Oncol. 32(5), S1283–S1346 (2021). •• Final analysis results of the KEYNOTE-355 trial, which was the main data source of this study.
Google Scholar
22. Duranti S, Fabi A, Filetti M et al. Breast Cancer Drug Approvals Issued by EMA: A Review of Clinical Trials. Cancers 13(20), 5189(2021). doi: 10.3390/cancers13205198
MedlineGoogle Scholar
23. Picot J, Kalita N, Gaisford W, Harris P, Onyimadu O, Cooper K. Fulvestrant for untreated hormone-receptor positive locally advanced or metastatic breast cancer: an Evidence Review Group perspective of a NICE single technology appraisal. Pharmacoeconomics 37(6), 753–762 (2019).
MedlineGoogle Scholar
24. Huang M, Lou Y, Pellissier J et al. Cost effectiveness of pembrolizumab vs. standard-of-care chemotherapy as first-line treatment for metastatic NSCLC that expresses high levels of PD-L1 in the United States. Pharmacoeconomics 35(8), 831–844 (2017).
MedlineGoogle Scholar
25. Huang M, Lopes GL, Insinga RP et al. Cost–effectiveness of pembrolizumab versus chemotherapy as first-line treatment in PD-L1-positive advanced non-small-cell lung cancer in the USA. Immunotherapy 11(17), 1463–1478 (2019).
CASGoogle Scholar
26. Haiderali A, Huang M, Pan W, Fox GE, Maciel D, Frederickson A. Pembrolizumab plus chemotherapy for first-line treatment of advanced triple-negative breast cancer – a network meta-analysis.. J. Natl Compr. Canc. Netw. 20(3.5), Abstract HSR22-145 (2022). •• Network meta-analysis reporting the relative effectiveness of pembrolizumab plus nab-paclitaxel versus atezolizumab plus nab-paclitaxel
Google Scholar
27. Institute for Clinical and Economic Review. A Guide to ICER's Methods for Health Technology Assessment (27 October 2020). https://icer.org/wp-content/uploads/2021/01/ICER_HTA_Guide_102720.pdf.
Google Scholar
28. Latimer NR. Survival analysis for economic evaluations alongside clinical trials – extrapolation with patient-level data. [National Institute for Health and Care Excellence (NICE), London, Internet]. 2013 Mar. NICE DSU Technical Support Document No. 14. doi: 10.1177/0272989X12472398
Google Scholar
29. Eisenhauer EA, Therasse P, Bogaerts J et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur. J. Cancer 45(2), 228–247 (2009).
Medline CASGoogle Scholar
30. Rugo HS, Loi S, Adams S et al. PD-L1 immunohistochemistry assay comparison in atezolizumab plus nab-paclitaxel-treated advanced triple-negative breast cancer. J. Natl Cancer Inst. 113(12), 1733–1743 (2021). •• A substudy of IMpassion130 which provided the clinical outcome data for comparing PD-L1 (combined positive score ≥10) patients in this study with those in the KEYNOTE-355 trial.
MedlineGoogle Scholar
31. US Centers for Medicare & Medicaid Services. Physician Fee Schedule look-up tool (1 December 2021). www.cms.gov/Medicare/Medicare-Fee-for-Service-Payment/PFSlookup.
Google Scholar
32. Weng X, Huang X, Li H et al. First-line treatment with atezolizumab plus nab-paclitaxel for advanced triple-negative breast cancer: a cost–effectiveness analysis. Am. J. Clin. Oncol. 43(5), 340–348 (2020).
MedlineGoogle Scholar
33. Analysource. www.analysource.com/.
Google Scholar
34. Shaw JW, Johnson JA, Coons SJ. US valuation of the EQ-5D health states: development and testing of the D1 valuation model. Med. Care 43(3), 203–220 (2005).
MedlineGoogle Scholar
35. Hatswell AJ, Pennington B, Pericleous L, Rowen D, Lebmeier M, Lee D. Patient-reported utilities in advanced or metastatic melanoma, including analysis of utilities by time to death. Health Qual. Life Outcomes 12, 140 (2014).
MedlineGoogle Scholar
36. Huang M, Haiderali A, Hu P, Chaudhuri M, Pan W. Health utility in patients with previously untreated locally recurrent inoperable or metastatic TNBC. J. Natl Compr. Canc. Netw. 20(3.5), Abstract HSR22-146 (2022).
Google Scholar
37. Garassino MC, Martelli O, Broggini M et al. Erlotinib versus docetaxel as second-line treatment of patients with advanced non-small-cell lung cancer and wild-type EGFR tumours (TAILOR): a randomised controlled trial. Lancet Oncol. 14(10), 981–988 (2013).
Medline CASGoogle Scholar
38. US Centers for Medicare and Medical Services. Medicare 2017 costs at a glance (2017). www.medicare.gov/your-medicare-costs/medicare-costs-at-a-glance#collapse-4809.
Google Scholar
39. US Bureau of Labor Statistics. Consumer Price Index (October 2021). www.bls.gov/cpi/latest-numbers.htm.
Google Scholar
40. Merck & Co., Inc. KEYTRUDA prescribing information (December 2021). ( 7 December 2021). www.merck.com/product/usa/pi_circulars/k/keytruda/keytruda_pi.pdf .
Google Scholar
41. Genentech, Inc. TECENTRIQ Prescribing Information (January 2022). www.gene.com/download/pdf/tecentriq_prescribing.pdf
Google Scholar
42. Sieluk J, Yang L, Haiderali A, Huang M, Hirshfield KM. Systemic therapy survival and end-of-life costs for metastatic triple-negative breast cancer: retrospective SEER-Medicare study of women age ≥65 years. Future Oncol. 17(20), 2581–2592 (2021).
CASGoogle Scholar
43. Agency for Healthcare Research and Quality. Healthcare Cost and Utilization Project (HCUP). (2019) https://hcupnet.ahrq.gov/ .
Google Scholar
44. National Cancer Institute. National Cancer Institute SEER Data, 1973–2013. http://seer.cancer.gov/data.
Google Scholar
45. Leighl NB, Nirmalakumar S, Ezeife DA, Gyawali B. An arm and a leg: the rising cost of cancer drugs and impact on access. Am. Soc. Clin. Oncol. Educ. Book 41, 1–12 (2021).
MedlineGoogle Scholar
46. Dolgin E. Bringing down the cost of cancer treatment. Nature 555(7695), S26–S29 (2018).
Medline CASGoogle Scholar
47. Braithwaite RS, Meltzer DO, King Jr JT, Leslie D, Roberts MS. What does the value of modern medicine say about the $50,000 per quality-adjusted life-year decision rule? Med. Care 46(4), 349–356 (2008).
MedlineGoogle Scholar
48. Bertram MY, Lauer JA, Stenberg K, Edejer TTT. Methods for the economic evaluation of health care interventions for priority setting in the health system: An update from WHO CHOICE. Int. J. Health Policy Manag. 10(11), 673–677 (2021).
MedlineGoogle Scholar
49. KNOEMA. IMF World Economic Outlook (WEO). https://knoema.com/pjeqzh/gdp-per-capita-by-country-forecast-from-imf-2020-2024.
Google Scholar
50. Neumann PJ, Cohen JT, Weinstein MC. Updating cost–effectiveness – the curious resilience of the $50,000-per-QALY threshold. N. Engl. J. Med. 371(9), 796–797 (2014).
Medline CASGoogle Scholar
51. Won KA, Spruck C. Triple-negative breast cancer therapy: current and future perspectives (Review). Int. J. Oncol. 57(6), 1245–1261 (2020).
Medline CASGoogle Scholar
52. Chisaki Y, Kuwada Y, Matsumura C, Yano Y. Cost–effectiveness analysis of atezolizumab plus nab-paclitaxel for advanced PD-L1 positive triple-negative breast cancer in Japan. Clin. Drug. Investig. 41(4), 381–389 (2021).
MedlineGoogle Scholar
53. Phua LC, Lee SC, Ng K, Abdul Aziz MI. Cost–effectiveness analysis of atezolizumab in advanced triple-negative breast cancer. BMC Health Serv. Res. 20, 581 (2020).
MedlineGoogle Scholar
54. Seymour L, Bogaerts J, Perrone A et al. iRECIST: guidelines for response criteria for use in trials testing immunotherapeutics [published correction appears in Lancet Oncol. 2019 May;20(5):e242]. Lancet Oncol. 18(3), e143–e152 (2017).
MedlineGoogle Scholar

Vol. 14, No. 13

Supplemental Materials

Metrics

Downloaded 3,484 times

History

Received 5 April 2022

Accepted 16 June 2022

Published online 7 July 2022

Published in print September 2022

Information

Keywords

Supplementary data

To view the supplementary data that accompany this paper please visit the journal website at: www.futuremedicine.com/doi/suppl/10.2217/imt-2022-0082

Author contributions

All authors contributed to the study design and methodology, interpretation of the results and development and writing of the draft manuscript and approved the final version.

Financial & competing interests disclosure

This study was funded by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. M Huang, A Haiderali, W Pan and P Hu are employees of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA, the sponsor of this study and manuscript. Z Zhou are employees of Analysis Group, Inc., which received consulting fees from Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA in connection with this study. E Gray was an employee of Analysis Group, Inc., at the time this study was conducted. P Fasching reports personal fees from Novartis Pfizer, Daiichi-Sankyo, Astra Zeneca, Eisai, Merck Sharp & Dohme, Lilly Pierre Fabre, SeaGen, Roche, Hexal and Agendia, and grants from Biontech and Cepheid. J O’Shaughnessy receives consulting fees and/or honorarium from AbbVie Inc., Agendia, Amgen Biotechnology, Aptitude Health, AstraZeneca, Bayer, Bristol-Myers Squibb, Celgene Corporation, Clovis Oncology, Daiichi Sankyo, Eisai, G1 Therapeutics, Genentech, Gilead Sciences, GRAIL, Halozyme Therapeutics, Heron Therapeutics, Immunomedics, Ipsen Biopharmaceuticals, Lilly, Merck, Myriad, Nektar Therapeutics, Novartis, Pfizer, Pharmacyclics, Pierre Fabre Pharmaceuticals, Puma Biotechnology, Prime Oncology, Roche, Samsung Bioepis, Sanofi, Seagen, Syndax Pharmaceuticals, Synthon, Taiho Oncology and Takeda. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Medical writing assistance was provided by J Imai, an employee of Analysis Group, Inc., and was funded by Merck Sharp & Dohme Corp.

Data sharing statement

Several datasets were used for this analysis: (1) efficacy, safety, patient-reported outcomes and healthcare resource utilization data collected in phase III KEYNOTE-355 trial. The patient-level data are not publicly available, but the results of the trials have been presented in several publications. The trial results supporting the findings of this analysis are available within the article and its supplemental material. (2) Observational data from the SEER databases and other publications, for which references are provided in the article. (3) Cost data used in the model were obtained from CMS or other publications.

Open access

This work is licensed under the Attribution-NonCommercial-NoDerivatives 4.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/4.0/

PDF download