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Efficacy, safety, tolerability and price of newly approved drugs in solid tumors

  • Author Footnotes
    1 Contributed equality to the manuscript.
    Tristan A. Barnes
    Footnotes
    1 Contributed equality to the manuscript.
    Affiliations
    Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, Department of Medicine, University of Toronto, Toronto, Canada
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  • Author Footnotes
    1 Contributed equality to the manuscript.
    Eitan Amir
    Correspondence
    Corresponding author at: Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, 700 University Ave 7-721, Toronto, ON M5G 1Z5, Canada. Fax: +1 416 946 4563.
    Footnotes
    1 Contributed equality to the manuscript.
    Affiliations
    Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, Department of Medicine, University of Toronto, Toronto, Canada
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  • Arnoud J. Templeton
    Affiliations
    St. Claraspital, University of Basel, Basel, Switzerland
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  • Susana Gomez-Garcia
    Affiliations
    Department of Medical Oncology, Hospital Álvaro Cunqueiro – Estructura Organizativa de Xestión Integrada (EOXI) of Vigo, Spain
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  • Beatriz Navarro
    Affiliations
    Translational Oncology Unit, Albacete University Hospital and Centro Regional de Investigaciones Biomédicas (CRIB), Universidad de Castilla La Mancha (UCLM), Albacete, Spain
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  • Bostjan Seruga
    Affiliations
    Department of Medical Oncology, Institute of Oncology Ljubljana, Slovenia
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  • Alberto Ocana
    Affiliations
    Translational Oncology Unit, Albacete University Hospital and Centro Regional de Investigaciones Biomédicas (CRIB), Universidad de Castilla La Mancha (UCLM), Albacete, Spain
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  • Author Footnotes
    1 Contributed equality to the manuscript.
Published:April 09, 2017DOI:https://doi.org/10.1016/j.ctrv.2017.03.011

      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.

      Keywords

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