TY - JOUR
T1 - Cancer drugs for solid tumors approved by the EMA since 2014
T2 - an overview of pivotal clinical trials
AU - Lasala, Ruggero
AU - Logreco, Andrea
AU - Romagnoli, Alessia
AU - Santoleri, Fiorenzo
AU - Musicco, Felice
AU - Costantini, Alberto
N1 - Publisher Copyright:
© 2020, Springer-Verlag GmbH Germany, part of Springer Nature.
Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2020/6/1
Y1 - 2020/6/1
N2 - 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trial supporting the authorization, the trial itself may not have been necessarily well-controlled; the authorization was revoked for a drug because the trial did not confirm the benefits expected from confirmatory trials; while for 2 drugs, the evidence of efficacy yielded by the trials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.
AB - 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.
KW - Efficacy
KW - Marketing authorization
KW - Pivotal trials
KW - Solid tumors
KW - Targeted therapies
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U2 - 10.1007/s00228-020-02850-y
DO - 10.1007/s00228-020-02850-y
M3 - Article
C2 - 32125472
AN - SCOPUS:85081618527
VL - 76
SP - 843
EP - 850
JO - European Journal of Clinical Pharmacology
JF - European Journal of Clinical Pharmacology
SN - 0031-6970
IS - 6
ER -