The lack of head-to-head randomised trials and the consequences for patients and national health service: The case of non-small cell lung cancer.

INTRODUCTION: To introduce a drug to the market, it's not mandatory for it to be more effective and safer than the current treatment for the same condition. Consequently, head-to-head studies between the two best treatments for the same condition are not required, and this could result in a lack of information for patients, clinicians, and decision-makers. This study aims to evaluate the presence of head-to-head studies among the drugs used for the treatment of non-small cell lung cancer (NSCLC). METHODS: Taking into account the National Comprehensive Cancer Network (NCCN) guidelines updated to 2022, which list all available treatments for each NSCLC subtype, the search engine Pubmed and the platform clinicaltrials.gov were consulted to find all completed and ongoing head-to-head studies among various treatments for NSCLC. RESULTS: Among the anti-EGFR (epidermal growth factor receptor) drugs, 7 studies were found, with 6 completed and 5 registrational for drug commercialisation. No completed study to date has compared osimertinib and afatinib. For anti-ALK (anaplastic lymphoma kinase) drugs, 7 studies were found, with 5 completed. Alectinib, brigatinib, and lorlatinib have no completed comparison studies, but all were compared with crizotinib. Among various immunotherapy-based regimens, 5 studies were found, with only 1 completed. Therapeutic regimens based on pembrolizumab, atezolizumab, or the combination of nivolumab/ipilimumab have not been compared in studies published to date. CONCLUSION: There are few head-to-head studies comparing treatments for NSCLC; there are no such studies between the latest generation of drugs. Consequently, ambiguous areas exist due to the lack of comparative studies among the available evidence, preventing the clinician's choice of the most effective treatment and risking the patient receiving suboptimal therapy. Simultaneously, the price of the drug cannot be determined correctly, relying only on indirect evaluations from different trials. To dispel this uncertainty, it would be desirable to initiate a process that brings together the demands derived from clinical practice and clinical research to provide clinicians and patients with the best possible evidence.

[Clinical trials approved by Aifa for Covid-19: report of the main results to fill the unmet medical need.] / Le sperimentazioni cliniche approvate dall'Aifa per Covid-19: report dei risultati principali per colmare l'unmet medical need.

INTRODUCTION: the rapidity with which the Coronavirus epidemic emergency exploded took the scientific community by surprise, unprepared for such an event. The objective of this work is to evaluate, to date, the state of the art of the clinical trials approved by Aifa, analyzing the characteristics of the single completed and published trials and the authorization status for the use of the drugs under study in the treatment of Covid-19. MATERIALS AND METHODS: The protocols available for each clinical study were extrapolated from the Aifa website relating to the management of clinical trials in Italy during the Covid-19 emergency; the unique EudraCT and Nct codes were extrapolated from these, verifying their publication using the PubMed search engine, the ClinicalTrials.gov platform, the EU Clinical Trials Register portal and the website of the pharmaceutical company identified as the promoter of the study. The characteristics of the individual trials useful for the analysis were extracted from the published papers. Finally, a comparison was made between the studies relating to experimental drugs which were subsequently authorized for the Covid-19 indication and the studies relating to drugs which have not yet been authorized to date. RESULTS: In total, Aifa approved 94 between March 2020 and March 2022; of these, 22 are not listed on ClinicalTrials.gov; of the 72 trials listed on ClinicalTrials.gov, 31 (43%) were published, for a total of 25 drugs. Of the authorized and published trials, 26 report the "mortality endpoint". The most studied drugs are remdesivir and tocilizumab with 3 studies each, methylprednisone and molnupravir with 2. 14 studies are phase III, of these 12 used a drug as an experimental treatment which was then approved for Covid-19. Of the 41 trials present on ClinicalTrials.gov that have not yet been published, 21 are terminated. The drugs anakinra, remdesivir, molnupravir, regdanvimab, tocilizumab, AZD1222 vaccine have been updated/registered for Covid-19 indication; anakinra, baricitinib, tocilizumab and sarilumab have been included in the list of Law 648/96; remdesivir, canakinumab and ruxolitinib have been entered into compassionate use programmes. DISCUSSION AND CONCLUSIONS: The methods of early access to therapy have allowed an alternative to patients who are not eligible for the ongoing trials. The challenge that the scientific community has faced has strengthened the culture of evidence-based medicine.

Prevalence study on potential drug-drug interaction in cancer patients in Piacenza hospital's Onco-Haematology department.

Background Cancer patients can be a human model of potential drug interactions. Usually they receive a large number of different medications, including antineoplastic agents, drugs for comorbid illness and medication for supportive care, however information about these interactions are fragmented and poor. Objective We assessed a prospective study to evaluate the prevalence of drug interaction among patients hospitalized in the Onco-Haematology department, Hospital of Piacenza. Methods Data on drugs administered for cancer, comorbidities, or supportive care were collected from different computerized prescription software in use in the department; we compared them with a database to focus on the co-administration of drugs. A literature review was performed to identify major potential drug interaction and to classify them by level of severity and by strengths of scientific evidence. Results In this study 284 cancer patients were enrolled; patients had taken an average of seven drugs on each day of therapy plus chemotherapeutic agents, we identified 67 potential drug interactions. At least 53 patients had one potential drug interaction. Of all potential drug interactions 63 were classified as moderate severity and only four as major. In 55 cases chemotherapeutic agents were involved in possible interactions with supportive care drugs, meanwhile in 12 cases the potential drug interactions were between supportive care drugs. Conclusions In our centre, thanks to a computerized prescription software, integrated with caution alarm in case of possible interaction, we had a lower rate of potential drug interactions than the one from literature. It is possible to improve the software integrating the alarm with the potential drug interactions between chemotherapy agents and supportive care drugs.