Clinical benefit and cost of breakthrough cancer drugs approved by the US Food and Drug Administration.
American Society of Clinical Oncology (ASCO)
European Society for Medical Oncology (ESMO)
breakthrough therapy designation
clinical benefit
cost
value frameworks
Journal
Cancer
ISSN: 1097-0142
Titre abrégé: Cancer
Pays: United States
ID NLM: 0374236
Informations de publication
Date de publication:
01 10 2020
01 10 2020
Historique:
received:
22
01
2020
revised:
17
06
2020
accepted:
22
06
2020
pubmed:
23
7
2020
medline:
12
6
2021
entrez:
23
7
2020
Statut:
ppublish
Résumé
The clinical benefit and pricing of breakthrough-designated cancer drugs are uncertain. This study compares the magnitude of the clinical benefit and monthly price of new and supplemental breakthrough-designated and non-breakthrough-designated cancer drug approvals. A cross-sectional cohort comprised approvals of cancer drugs for solid tumors from July 2012 to December 2017. For each indication, the clinical benefit from the pivotal trials was scored via validated frameworks: the American Society of Clinical Oncology Value Framework (ASCO-VF), the American Society of Clinical Oncology Cancer Research Committee (ASCO-CRC), the European Society for Medical Oncology Magnitude of Clinical Benefit Scale (ESMO-MCBS), and the National Comprehensive Cancer Network (NCCN) Evidence Blocks. A high clinical benefit was defined as scores ≥ 45 for the ASCO-VF, overall survival gains ≥ 2.5 months or progression-free survival gains ≥ 3 months for all cancer types for the ASCO-CRC criteria, a grade of A or B for trials of curative intent and a grade of 4 or 5 for trials of noncurative intent for the ESMO-MCBS, and scores of 4 and 5 and a combined score ≥ 16 for the NCCN Evidence Blocks. Monthly Medicare drug prices were calculated with Medicare prices and DrugAbacus. This study identified 106 trials supporting approval of 52 drugs for 96 indications. Forty percent of these indications received the breakthrough designation. Among the included trials, 33 (43%), 46 (73%), 35 (34%), and 67 (69%) met the thresholds established by the ASCO-VF, ASCO-CRC, ESMO-MCBS, and NCCN, respectively. In the metastatic setting, there were higher odds of clinically meaningful grades in trials supporting breakthrough drugs with the ASCO-VF (odds ratio [OR], 3.69; P = .022) and the NCCN Evidence Blocks (OR, 5.80; P = .003) but not with the ASCO-CRC (OR, 3.54; P = .11) or version 1.1 (v1.1) of the ESMO-MCBS (OR, 1.22; P = .70). The median costs of breakthrough therapy drugs were significantly higher than those of nonbreakthrough therapies (P = .001). In advanced solid cancers, drugs that received the breakthrough therapy designation were more likely than nonbreakthrough therapy drugs to be scored as providing a high clinical benefit with the ASCO-VF and the NCCN Evidence Blocks but not with the ESMO-MCBS v1.1 or the ASCO-CRC scale.
Sections du résumé
BACKGROUND
The clinical benefit and pricing of breakthrough-designated cancer drugs are uncertain. This study compares the magnitude of the clinical benefit and monthly price of new and supplemental breakthrough-designated and non-breakthrough-designated cancer drug approvals.
METHODS
A cross-sectional cohort comprised approvals of cancer drugs for solid tumors from July 2012 to December 2017. For each indication, the clinical benefit from the pivotal trials was scored via validated frameworks: the American Society of Clinical Oncology Value Framework (ASCO-VF), the American Society of Clinical Oncology Cancer Research Committee (ASCO-CRC), the European Society for Medical Oncology Magnitude of Clinical Benefit Scale (ESMO-MCBS), and the National Comprehensive Cancer Network (NCCN) Evidence Blocks. A high clinical benefit was defined as scores ≥ 45 for the ASCO-VF, overall survival gains ≥ 2.5 months or progression-free survival gains ≥ 3 months for all cancer types for the ASCO-CRC criteria, a grade of A or B for trials of curative intent and a grade of 4 or 5 for trials of noncurative intent for the ESMO-MCBS, and scores of 4 and 5 and a combined score ≥ 16 for the NCCN Evidence Blocks. Monthly Medicare drug prices were calculated with Medicare prices and DrugAbacus.
RESULTS
This study identified 106 trials supporting approval of 52 drugs for 96 indications. Forty percent of these indications received the breakthrough designation. Among the included trials, 33 (43%), 46 (73%), 35 (34%), and 67 (69%) met the thresholds established by the ASCO-VF, ASCO-CRC, ESMO-MCBS, and NCCN, respectively. In the metastatic setting, there were higher odds of clinically meaningful grades in trials supporting breakthrough drugs with the ASCO-VF (odds ratio [OR], 3.69; P = .022) and the NCCN Evidence Blocks (OR, 5.80; P = .003) but not with the ASCO-CRC (OR, 3.54; P = .11) or version 1.1 (v1.1) of the ESMO-MCBS (OR, 1.22; P = .70). The median costs of breakthrough therapy drugs were significantly higher than those of nonbreakthrough therapies (P = .001).
CONCLUSIONS
In advanced solid cancers, drugs that received the breakthrough therapy designation were more likely than nonbreakthrough therapy drugs to be scored as providing a high clinical benefit with the ASCO-VF and the NCCN Evidence Blocks but not with the ESMO-MCBS v1.1 or the ASCO-CRC scale.
Substances chimiques
Antineoplastic Agents
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
4390-4399Subventions
Organisme : Arnold Ventures
Organisme : Harvard-MIT Center for Regulatory Science
Commentaires et corrections
Type : ErratumIn
Informations de copyright
© 2020 American Cancer Society.
Références
Garon EB, Rizvi NA, Hui R, et al. Pembrolizumab for the treatment of non-small-cell lung cancer. N Engl J Med. 2015;372:2018-2028.
Flaherty KT, Infante JR, Daud A, et al. Combined BRAF and MEK inhibition in melanoma with BRAF V600 mutations. N Engl J Med. 2012;367:1694-1703.
Reck M, Rodriguez-Abreu D, Robinson AG, et al. Pembrolizumab versus chemotherapy for PD-L1-positive non-small-cell lung cancer. N Engl J Med. 2016;375:1823-1833.
Robert C, Karaszewska B, Schachter J, et al. Improved overall survival in melanoma with combined dabrafenib and trametinib. N Engl J Med. 2015;372:30-39.
Pub L No. 112-144, §902, 126 Stat 993 (2012).
US Food and Drug Administration. Guidance for Industry: Expedited Programs for Serious Conditions-Drugs and Biologics. Published May 2014. Accessed July 11, 2020. http://www.fda.gov/downloads/drugs/guidancecomplianceregulatoryinformation/guidances/ucm358301.pdf
US Food and Drug Administration. Manual of Policies and Procedures-Good Review Practice: Review of Marketing Applications for Breakthrough Therapy-Designated Drugs and Biologics That Are Receiving an Expedited Review. Published March 9, 2015. Accessed July 11, 2020. https://www.fda.gov/media/90933/download
US Food and Drug Administration. Breakthrough therapy at FDA. Accessed July 11, 2020. https://www.fda.gov/media/95302/download
Darrow JJ, Avorn J, Kesselheim AS. The FDA breakthrough-drug designation-four years of experience. N Engl J Med. 2018;378:1444-1453.
Bach PB. Limits on Medicare's ability to control rising spending on cancer drugs. N Engl J Med. 2009;360:626-633.
Mailankody S, Prasad V. Five years of cancer drug approvals: innovation, efficacy, and costs. JAMA Oncol. 2015;1:539-540.
Hwang TJ, Franklin JM, Chen CT, et al. Efficacy, safety, and regulatory approval of Food and Drug Administration-designated breakthrough and nonbreakthrough cancer medicines. J Clin Oncol. 2018;36:1805-1812.
Ellis LM, Bernstein DS, Voest EE, et al. American Society of Clinical Oncology perspective: raising the bar for clinical trials by defining clinically meaningful outcomes. J Clin Oncol. 2014;32:1277-1280.
Schnipper LE, Davidson NE, Wollins DS, et al. Updating the American Society of Clinical Oncology Value Framework: revisions and reflections in response to comments received. J Clin Oncol. 2016;34:2925-2934.
Cherny NI, Dafni U, Bogaerts J, et al. ESMO-Magnitude of Clinical Benefit Scale version 1.1. Ann Oncol. 2017;28:2340-2366.
Carlson RW, Jonasch E. NCCN Evidence Blocks. J Natl Compr Canc Netw. 2016;14:616-619.
Mateo J, Chakravarty D, Dienstmann R, et al. A framework to rank genomic alterations as targets for cancer precision medicine: the ESMO Scale for Clinical Actionability of Molecular Targets (ESCAT). Ann Oncol. 2018;29:1895-1902.
US Food and Drug Administration. Drugs at Food and Drug Administration. Accessed July 11, 2020. http://www.fda.gov/Drugs/InformationOnDrugs/ApprovedDrugs/ucm279174.htm
Tibau A, Molto C, Ocana A, et al. Magnitude of clinical benefit of cancer drugs approved by the US Food and Drug Administration. J Natl Cancer Inst. 2018;110:486-492.
Tibau A, Molto C, Borrell M, et al. Magnitude of clinical benefit of cancer drugs approved by the US Food and Drug Administration based on single-arm trials. JAMA Oncol. 2018;4:1610-1611.
US Food and Drug Administration. Review classification new drug applications. Accessed July 11, 2020. https://www.fda.gov/Drugs/DevelopmentApprovalProcess/HowDrugsareDevelopedandApproved/DrugandBiologicApprovalReports/NDAandBLAApprovalReports/ucm373420.htm
US Food and Drug Administration. Review classification supplement drug applications. Accessed July 11, 2020. http://www.fda.gov/Drugs/DevelopmentApprovalProcess/HowDrugsareDevelopedandApproved/DrugandBiologicApprovalReports/NDAandBLAApprovalReports/ucm2007013.htm
US Food and Drug Administration. Orphan drugs. Accessed July 11, 2020. http://www.accessdata.fda.gov/scripts/opdlisting/oopd/index.cfm
US Food and Drug Administration. Accelerated drugs. Accessed July 11, 2020. https://www.fda.gov/Drugs/DevelopmentApprovalProcess/HowDrugsareDevelopedandApproved/DrugandBiologicApprovalReports/NDAandBLAApprovalReports/ucm373430.htm
US Food and Drug Administration. List of cleared or approved companion diagnostic devices (in vitro and imaging tools). Accessed July 11, 2020. https://www.fda.gov/MedicalDevices/ProductsandMedicalProcedures/InVitroDiagnostics/ucm301431.htm
US Food and Drug Administration. Drugs@FDA: FDA-approved drugs. Accessed July 11, 2020. http://www.accessdata.fda.gov/scripts/cder/drugsatfda/
Memorial Sloan Kettering Cancer Center. DrugAbacus. Accessed July 11, 2020. http://abacus.realendpoints.com/abacus-mskcc?ab-eff=1000&ab-tox=0.1&ab-nov=1&ab-rare=1&ab-pop=1&ab-dev=1&ab-prog=1.0&ab-need=1&ab-time=1501410712
US Centers for Medicare and Medicaid Services. 2018 ASP Drug Pricing Files. Accessed July 11, 2020. https://www.cms.gov/Medicare/Medicare-Fee-for-Service-Part-B-Drugs/McrPartBDrugAvgSalesPrice/2018ASPFiles.html
US Centers for Medicare and Medicaid Services. Medicare Plan Finder. Accessed July 11, 2020. https://www.medicare.gov/find-a-plan/questions/home.aspx
National Comprehensive Cancer Network. NCCN Guidelines. Accessed July 11, 2020. https://www.nccn.org/professionals/physician_gls/default.aspx
Cherny NI, de Vries EGE, Dafni U, et al. Comparative assessment of clinical benefit using the ESMO-Magnitude of Clinical Benefit Scale version 1.1 and the ASCO Value Framework Net Health Benefit Score. J Clin Oncol. 2019;37:336-349.
Monthly and median costs of cancer drugs at the time of FDA approval 1965-2016. J Natl Cancer Inst. 2017;109:djx173.
Puthumana J, Wallach JD, Ross JS. Clinical trial evidence supporting FDA approval of drugs granted breakthrough therapy designation. JAMA. 2018;320:301-303.
Del Paggio JC, Sullivan R, Schrag D, et al. Delivery of meaningful cancer care: a retrospective cohort study assessing cost and benefit with the ASCO and ESMO frameworks. Lancet Oncol. 2017;18:887-894.
Shepshelovich D, Tibau A, Goldvaser H, et al. Postmarketing modifications of drug labels for cancer drugs approved by the US Food and Drug Administration between 2006 and 2016 with and without supporting randomized controlled trials. J Clin Oncol. 2018;36:1798-1804.
Vokinger KN, Hwang TJ, Grischott T, et al. Prices and clinical benefit of cancer drugs in the USA and Europe: a cost-benefit analysis. Lancet Oncol. 2020;21:664-670.
Seruga B, Templeton AJ, Badillo FE, et al. Under-reporting of harm in clinical trials. Lancet Oncol. 2016;17:e209-e219.
Davis C, Naci H, Gurpinar E, et al. Availability of evidence of benefits on overall survival and quality of life of cancer drugs approved by European Medicines Agency: retrospective cohort study of drug approvals 2009-13. BMJ. 2017;359:j4530.
Beaver JA, Howie LJ, Pelosof L, et al. A 25-year experience of US Food and Drug Administration accelerated approval of malignant hematology and oncology drugs and biologics: a review. JAMA Oncol. 2018;4:849-856.