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Cancer drugs for solid tumors approved by the EMA since 2014: an overview of pivotal clinical trials

European Journal of Clinical Pharmacology volume 76, pages 843–850 (2020)Cite this article

Abstract

Introduction

The European Medicine Agency (EMA) authorizes the marketing of drugs, with the authorization being full, conditional or issued under exceptional circumstances. Usually the efficacy and safety of drugs must be demonstrated in at least 2 well-controlled trials, but this rule is not always observed. The objective of the trial is to provide an overview of the pivotal trials of cancer drugs authorized for marketing in Europe since 2014.

Materials and methods

From the technical data sheets of each drug authorized by the EMA between January 1, 2014 and May 31, 2019, we evaluated the relative pivotal trial(s) in terms of the following characteristics: number of patients, masking, trial phase, number of arms, primary endpoint(s), presence of subgroup analysis, quality of life as endpoint, and value of statistical p. The results provided us with the total number of trials, which we then divided into trials for orphan and non-orphan drugs.

Results

We considered 38 medicines, 6 of which were classified as orphans, for a total of 96 pivotal trials. Four drugs had conditional authorization, 1 was authorized under exceptional circumstances. Seventeen drugs underwent only 1 pivotal trial to support marketing authorization. Most of the trials were phase 3 and open-label, with 2 arms. Most trials considered the progression-free survival (PFS) as the primary endpoint, less than 30% of trials consider OS as a primary endpoint, and less than 40% of trials reported quality of life. The p values, with very few exceptions, were below 0.05.

Conclusions

The rule of 2 well-controlled trials was complied with in just over 50% of the authorized drugs, and even when there was only 1 pivotal trial supporting the authorization, the trial itself may not have been necessarily well-controlled; the authorization was revoked for a drug because the trial did not confirm the benefits expected from confirmatory trials; while for 2 drugs, the evidence of efficacy yielded by the trials was not considered exhaustive. Considering that sometimes clinical authorization trials do not provide complete data on safety and efficacy, it would be perhaps appropriate to gather more pre-marketing evidence or leverage post-marketing data to complete the available information and have greater certainty.

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Author information

Affiliations

  1. Hospital Pharmacy of Corato, Local Health Unit of Bari, Bari, Italy

    Ruggero Lasala

  2. Medicinal Products Authorization Department, Italian Medicine Agency, Rome, Italy

    Andrea Logreco

  3. Pharmacy of Spirito Santo Hospital, Pescara, Italy

    Alessia Romagnoli, Fiorenzo Santoleri & Alberto Costantini

  4. Hospital Pharmacy, IFO Regina Elena San Gallicano, Rome, Italy

    Felice Musicco

Authors
  1. Ruggero Lasala
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  2. Andrea Logreco
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  3. Alessia Romagnoli
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  4. Fiorenzo Santoleri
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  5. Felice Musicco
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  6. Alberto Costantini
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Contributions

Ruggero Lasala made contribution to the conception and design, acquisition of data, analysis and interpretation of data, and article writing.

Andrea Logreco, Alessia Romagnoli, Fiorenzo Santoleri Felice Musicco, and Alberto Costantini made contribution to the acquisition of data, analysis and interpretation of data, and article writing.

Corresponding author

Correspondence to Ruggero Lasala.

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Lasala, R., Logreco, A., Romagnoli, A. et al. Cancer drugs for solid tumors approved by the EMA since 2014: an overview of pivotal clinical trials. Eur J Clin Pharmacol 76, 843–850 (2020). https://doi.org/10.1007/s00228-020-02850-y

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  • DOI: https://doi.org/10.1007/s00228-020-02850-y

Keywords

  • Pivotal trials
  • Marketing authorization
  • Solid tumors
  • Targeted therapies
  • Efficacy