Systematic or Meta-analysis Studies
Efficacy, safety, tolerability and price of newly approved drugs in solid tumors

https://doi.org/10.1016/j.ctrv.2017.03.011Get rights and content

Highlights

  • Cytotoxic drugs had lesser efficacy relative to control, than targeted, anti-angiogenic and immunotherapy agents.

  • Immunotherapy has better safety and tolerability compared to other classes of antineoplastic agents.

  • Drug prices have increased by 13% each year from 2000 to 2015, without significant differences between classes of drugs.

  • There is little to no correlation between efficacy and price of newly approved drugs.

Abstract

Background

New anti-cancer drugs utilize diverse mechanisms of action. Here we evaluate their differential efficacy, safety, tolerability and price.

Methods

Drugs approved for solid tumor treatment between 2000 and 2015 were identified and analyzed in subgroups: agents targeting oncogenes (group 1), anti-angiogenics (group 2), immunotherapy (group 3), and chemotherapy (group 4). Hazard ratios (HRs) were extracted from the registration trials and pooled in a meta-analysis. Odds ratios for toxic death, treatment discontinuation and grade 3–4 toxicity were compared to control groups. The Micromedex Red Book was used to calculate the monthly price.

Results

Analysis included 74 studies comprising 48,527 patients. Progression-free survival (PFS) was improved to a greater degree with groups 1 and 2 than with groups 3 and 4, (pooled HR: 0.54, 0.56, 0.63, and 0.76 for groups 1–4 respectively, p for difference <0.001). Compared to PFS, there was a lower magnitude of improvement overall survival in all groups and the degree of benefit was less for group 4 than for other groups (pooled HR: 0.77, 0.78, 0.68, and 0.83 for groups 1–4 respectively, p for difference = 0.007). Compared to control groups in individual trials, immunotherapy was associated with better safety and tolerability than other groups. Drug prices have increased over time with no significant difference between groups. There was no meaningful correlation between pricing and efficacy.

Conclusions

Compared to control groups, immunotherapeutics and drugs targeting oncogenes or angiogenesis improve efficacy to a greater degree than chemotherapy. Immunotherapy appears to have better safety and tolerability profile compared to other cancer therapies. Market price of drugs is not related to efficacy.

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)

  • L.E. Schnipper

    American society of clinical oncology statement: a conceptual framework to assess the value of cancer treatment options

    J Clin Oncol

    (2015)
  • FDA. FDA Approved Drugs for Oncology. 2016 [cited 2016 21-Aug-2016]. Available from:...
  • Red Book - Healthcare Drug Pricing Resource

    Micromedex 2.0

    (2016)
  • FDA. In Vitro Companion Diagnostic Devices. August 6, 2014 [cited 2016 16-Nov]; [FDA]. Available from:...
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