Clinical trials of new cancer-targeted therapies and immunotherapies often fail to report treatment-related adverse events, particularly the duration of the adverse events and recurrent or late toxicities, according to a recent Italian study.
The study, “Systematic review of adverse events reporting in clinical trials leading to approval of targeted therapy and immunotherapy,” was presented at the European Society of Medical Oncology (ESMO) 2016 Congress, Oct. 10, in Copenhagen.
Improved understanding of cancer pathogenesis the past few years has given rise to new treatment options, including targeted therapies and cancer immunotherapies. Targeted therapies aim to inhibit molecular pathways that are crucial for tumor growth and maintenance, whereas immunotherapies stimulate the immune system to actively recognize and kill the tumor cells. However, these cancer treatment approaches may trigger unexpected adverse events, or treatment side effects, which need to be adequately reported in clinical trials.
“Reporting adverse events from clinical trials with new agents is a crucial point, as this will inform physicians and patients regarding the safety profile of that drug and what to expect when starting this therapy in a new patient in everyday clinical practice,” Paolo Bossi, MD, lead researcher, from the Head & Neck Unit at the Fondazione IRCCS – Istituto Nazionale dei Tumori, Milan, said in a news release.
Bossi and colleagues conducted a systematic review of 81 published clinical trials evaluating target therapies and immunotherapies in adults with solid tumors. The drugs tested in these trials were all approved by the U.S. Food and Drug Administration (FDA) between 2000 and 2015 for adult patients with solid tumors.
The team evaluated each study according to a 24-point score card based on the Consolidated Standards of Reporting Trials (CONSORT) guidance, an evidence-based set of recommendations for reporting randomized trials.
Ninety percent of the trials failed to report recurrent and late toxicities adequately, researchers found. The time of occurrence of adverse events (AEs) was explained inadequately in 86% of trials, and 75% of the studies reported AEs occurring only above a fixed threshold.
In addition, in more than 50% of the analyzed studies, descriptions of toxicities that led to therapy withdrawal and reporting of follow-up assessment, were limited. Also, one-third of the studies failed to report dose reductions due to AEs.
“Toxicities of targeted agents and immunotherapy are obviously different from the toxicities we are used to observing and treating due to chemotherapy, and there are some aspects of the toxicities of these newer agents that we are not so well informed about,” Bossi said.
During his presentation, Bossi emphasised that with the introduction of new measures, there have been improvements in reporting the duration of an adverse event — also known as the “third axis” along with severity and frequency — allowing for an easier and more accurate measurement and assessment of treatment toxicities.
The National Cancer Institute (NCI) of the National Institutes of Health (NIH) has published standardized definitions for AEs, known as the Common Terminology Criteria for Adverse Events (CTCAE) to describe the severity of organ toxicity for patients receiving cancer therapy. Patients can use the Patient-Reported Outcomes version of the CTCAE (PRO-CTCAE).
“The most important and innovative one is the PRO-CTCAE form, which is the patient-reported outcome version of the common toxicity criteria of adverse events, and which will allow physicians to collect the symptoms as reported by the patients, considering also the severity, intensity and influence of the symptoms on their quality of life.”
Commenting on the study, Nathan Cherny, MD, from the Shaare Zedek Medical Center in Jerusalem, said “It ought to be remembered that there is pre-existing evidence that toxicity reporting based upon clinician reports, rather than patient-reported data, consistently leads to underreporting of adverse events and the severity of those events.”
“These findings lend further support to the proposal to radically re-evaluate the collection and reporting of adverse event data to give weighting to patient-reported data,” Cherny said. “It is worth noting, however, that the published reports of studies represent a summary of a dataset that may not necessarily represent the full data set submitted to licensing authorities for purposes of drug approval and registration,” he said.
