320P - Systematic review of adverse events reporting in clinical trials leading to approval of targeted therapy and immunotherapy

Date 10 October 2016
Event ESMO 2016 Congress
Session Poster display
Topics Clinical Research
Basic Scientific Principles
Presenter Paolo Bossi
Citation Annals of Oncology (2016) 27 (6): 100-102. 10.1093/annonc/mdw366
Authors P. Bossi1, L. Botta2, P. Bironzo3, C. Sonetto3, G. Musettini4, A. Sbrana4, V. Di Giannantonio1, L. Locati1, M. Di Maio5, A. Antonuzzo4
  • 1Head & Neck Unit, Fondazione IRCCS - Istituto Nazionale dei Tumori, 20133 - Milano/IT
  • 2Evaluative Epidemiology, Preventive And Predictive Medicine, Fondazione IRCCS - Istituto Nazionale dei Tumori, 20133 - Milano/IT
  • 3Medical Oncology, Azienda Ospedaliero-Universitaria ASOU San Luigi Gonzaga, Orbassano/IT
  • 4Medical Oncology, Azienda Ospedaliera Universitaria S.Chiara, 56100 - Pisa/IT
  • 5Medical Oncology, Università di Torino, Ospedale Mauriziano, Torino/IT



Reporting toxicities of targeted therapies (TTs) and immunotherapy in oncology requires care in respect to way of measurement, duration of adverse events (AEs) and impact on treatment dose intensity.

New drugs are approved by regulatory agencies on the basis of the safety and efficacy results deriving from pivotal trials, but the impact on broader use is often misunderstood.


We identified the TTs and immunotherapies approved by FDA for solid malignancies in adult patients from 2000 to Oct 2015. The trials which led to this indication were retrieved from the FDA website.

Publications were reviewed according to a 24-point score based on the Consolidated Standards of Reporting Trials (CONSORT) guidance.


We identified 81 trials, mainly performed in colorectal, lung, breast cancer and melanoma, globally involving more than 45.000 patients. The experimental drug was studied as single agent in 51% of the cases and associated with chemotherapy in 32%; setting of trials was mainly the treatment of advanced disease (95% of the trials).

When specified, the median rate of elderly population (> 65 years) who were treated was 37%.

The items that reported the higher proportion of trials with a low score in AEs description are the following: reporting recurrent and late toxicities and duration of the AEs (in more than 90% of the trials); description of time of occurrence (86% of the trials) and indication of all AEs, instead of only those occurred with a frequency above a fixed threshold (75% of the trials) Limitations in methods for presenting AEs, in description of the toxicities leading to therapy withdrawal and in follow up interval assessment were present in more than 50% of the analysed papers. Dose reductions due to AEs were not reported in 1 out of 3 trials.


Suboptimal reporting of AEs in trials leading to approval of TTs and immunotherapy was shown. Improving AEs caption and description should be a priority in ongoing trials as well as post-marketing safety analysis. This is particularly true for AEs of new drugs, frequently mild or moderate in severity but potentially longer in duration and recurrent, with a clear impact on patients' quality of life.

Clinical trial identification

Legal entity responsible for the study

Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy




All authors have declared no conflicts of interest.