Systematic or Meta-analysis StudiesEfficacy, safety, tolerability and price of newly approved drugs in solid tumors
Introduction
Regulatory approval of anti-cancer drugs occurs typically after demonstration of clinical benefit in registration trials. Over the last 15 years, new drug development has focused on numerous mechanisms of action including conventional cytotoxic agents, inhibition of oncogenic signaling pathways, angiogenesis and immune modulation. In recent years, there has been substantial enthusiasm for immunotherapy agents [1], [2], [3], [4]. However, the differential efficacy, safety, tolerability and price of these agents relative to other anti-neoplastic drugs are uncertain.
There is increasing recognition of the importance of value in the oncology drug market [5]. The major oncology societies, American Society of Clinical Oncology (ASCO) and European Society of Medical Oncology (ESMO), have released position statements and papers outlining approaches to quantifying clinical benefit and value. These have focused on the balance between efficacy, safety and tolerability of a drug and its cost [6], [7]. The pricing of drugs is relevant to the sustainability of health care systems, with pressures on private insurers and public funding bodies to pay for new medications.
Here, we examine differences in efficacy, safety, tolerability and market price of approved anticancer drugs comparing mechanistically defined subgroups of medications. We hypothesized that despite differing enthusiasm; there would be limited differences in efficacy between different anti-cancer drugs and that there would be no association between their efficacy and cost.
Section snippets
Search strategy
The Drugs@FDA [8] website was searched for new drug approvals by the United States Food and Drug Administration (FDA) for the treatment of solid tumors between 2000 and 2015. Included agents were those with specific anti-neoplastic activity. Supportive care medications were excluded. We assessed the drug labels of included agents for the referenced clinical trial supporting registration. Trials were included in the analysis if they were randomized and reported a hazard ratio (HR) for a
Results
A total of 74 studies comprising 48,527 patients were included in the analysis. Characteristics of included trials are shown in Table 1.
Discussion
Drug development over the last 2 decades has resulted in anti-cancer drugs utilizing multiple mechanisms of action including conventional cytotoxic agents, inhibition of oncogenic signaling pathways, angiogenesis and immune modulation. However, the differential efficacy, safety, tolerability and market price of approved anticancer drugs in these mechanistically defined subgroups has not been reported.
In this article we report that when comparing these groups there is a lower pooled HR
Authors’ disclosures
The authors indicate no potential conflicts of interest.
Funding source
There was no funding source for this research.
Authors’ contributions
Conception and design: EA, AO.
Collection and assembly of data: TB, EA, SG, BN, AO.
Data Analysis and interpretation: TB, EA.
Manuscript writing: All authors.
Final approval of manuscript: All authors.
Acknowledgements
We would like to acknowledge Ian F. Tannock for his support and constructive comments.
References (29)
A standardised, generic, validated approach to stratify the magnitude of clinical benefit that can be anticipated from anti-cancer therapies: the European Society for Medical Oncology Magnitude of Clinical Benefit Scale (ESMO-MCBS)
Ann Oncol
(2015)- et al.
Meta-analysis in clinical trials
Control Clin Trials
(1986) Poor correlation between progression-free and overall survival in modern clinical trials: are composite endpoints the answer?
Eur J Cancer
(2012)A systematic review of immune-related adverse event reporting in clinical trials of immune checkpoint inhibitors
Ann Oncol
(2015)Toxicities of the anti-PD-1 and anti-PD-L1 immune checkpoint antibodies
Ann Oncol
(2015)Immunotherapy to treat cancer
Clin Pharmacol Ther
(2016)Scientists unleash the power of immunotherapy on stubborn cancers
- et al.
Immune checkpoint blockade in cancer therapy
J Clin Oncol
(2015) - Grady D. Harnessing the Immune Susterm to Fight Cancer. The New York Times 2016 July 31 2016; A1. Available from:...
The value of considering cost, and the cost of not considering value
J Clin Oncol
(2016)
American society of clinical oncology statement: a conceptual framework to assess the value of cancer treatment options
J Clin Oncol
Micromedex 2.0
Cited by (40)
A water-dependent reversible photoacidity strategy for cancer treatment
2022, European Journal of Medicinal ChemistryCitation Excerpt :Results showed that W-RPAT mediated by TQs-Th-PEG5 NPs achieved a slightly better tumor suppression effect than PDT mediated by KAE in group A. Therefore, in the treatment of larger tumors (hypoxic tumors) in group B, W-RPAT has a significant advantage due to the O2-independent characteristic. Safety must be the first consideration in evaluating any new treatment method, especially for methods involving injectable pharmaceuticals [20,21]. To determine whether W-RPAT had side effects, the lungs, livers, spleens, kidneys, and hearts of tumor-bearing mice in the W-RPAT group and control group were excised and sectioned 7 days after W-RPAT for H&E staining.
Recent trends in biodegradable polyester nanomaterials for cancer therapy
2021, Materials Science and Engineering CCitation Excerpt :The current diagnostic and prognostic markers are not sufficient for the successful detection and treatment of cancer [2,3]. Most importantly, majority of the anti-cancer agents are not specific in targeting the cancer cells thus resulting in higher systemic toxicity and adverse effects on various organs [4]. However, the early detection of cancer is very crucial to achieve the successful treatment and to reduce the disease mortality [5].
3D culture systems as models for solid tumors and cancer metabolism
2020, Biomaterials for 3D Tumor ModelingRegulating diagnosis—Molecular and regulatory sub-stratifications of lung cancer treatment
2024, Sociology of Health and IllnessAnalysis of oncological drugs authorised in Spain in the last decade: association between clinical benefit and reimbursement
2024, European Journal of Health Economics
- 1
Contributed equality to the manuscript.