| dc.description.abstract | Background
Progression-Free Survival (PFS) is increasingly being used as the primary efficacy endpoint in registrational clinical trials in advanced cancer because it is available earlier than Overall Survival (OS) and it is not affected by post-progression treatments. In clinical practice, patients are assessed less frequently and according to less strict protocols compared to clinical trials. These discrepancies in the assessments might impact on the comparison of PFS outcomes between clinical trials and observational studies and subsequently on the evaluation of the efficacy-effectiveness gap.
Aim
The primary aim of this scoping review is to provide an overview of the methods of PFS assessment in observational studies investigating the effect of immunotherapy-based treatments in advanced Non-Small Cell Lung Cancer (NSCLC). The secondary aim is to compare these methods with the already identified methods of PFS assessment in clinical trials and explore the potential impact of the differences on establishing the efficacy/effectiveness of anticancer treatments in advanced NSCLC.
Methods
Pubmed and Embase were searched for phase III clinical trials and observational studies evaluating the effect of immunotherapy-based treatments in advanced NSCLC between 2012 and 2023. The study characteristics and the variables of the PFS assessment methods, comprising the assessment schedule, the imaging modality, the interpreter of the scan, the criteria for progression and the PFS definition were extracted and reported for the clinical trials and the observational studies.
Results
A total of 34 clinical trials and 123 observational studies were included in this report. All clinical trials reported information on the assessment schedule which was highly detailed in all cases. In the 57 (46%) observational studies that reported information on the assessment schedule, 33 (58%) studies used a highly detailed description. Information on the imaging modality was reported in 33 (97%) clinical trials and in 58 (47%) observational studies, and in these studies, (PET-)CT and/or MRI was used in 33 (100%) trials and in 51 (88%) observational studies. The criteria for progression were reported in 33 (97%) clinical trials and in 109 (89%) observational studies. Among the studies that used radiological criteria, 32 (97%) clinical trials and 89 (84%) observational studies used RECIST 1.1. The events included in the PFS definition were reported in 33 (97%) clinical trials and in 99 (80%) observational studies. Of all these studies, PFS was considered as composite endpoint of progressive disease and death in 32 (97%) clinical trials and in 82 (83%) observational studies. In 13 (13%) observational studies, only progressive disease was considered a PFS event.
Conclusions
Overall, the methods of PFS assessment differ considerably between the clinical trials and the observational studies, with the latter having lower reporting rates, less detailed reporting and higher variability for all PFS assessment variables. These results underscore the challenges when comparing PFS outcomes of different studies and point to the need for intensification of the efforts for a more complete and detailed reporting of the PFS assessment methods. | |
