# Definitions, measurement, and reporting of progression-free survival in randomized clinical trials and observational studies of patients with advanced non-small-cell lung cancer treated with immunotherapy: a scoping review

## TL;DR

This study reviews how progression-free survival is defined and measured in clinical trials and observational studies of lung cancer immunotherapy, finding inconsistencies that make comparisons difficult.

## Contribution

The study identifies specific gaps in how observational studies report progression-free survival compared to clinical trials.

## Key findings

- Most observational studies lack detailed reporting on PFS measurement end dates, imaging types, and reviewers.
- PFS definitions and measurements in observational studies often differ from those in clinical trials.
- Aligning PFS criteria between observational studies and clinical trials is needed for better comparison.

## Abstract

Evidence from observational studies is increasingly used in oncology to complement evidence from clinical trials. Commonly used endpoints to evaluate oncology medicines are overall survival (OS) and progression-free survival (PFS). However, comparing PFS across observational studies and with clinical trials can be challenging due to differences in its definition and measurement. This scoping review investigated how PFS was defined, measured, and reported in randomized clinical trials (RCTs) and observational studies of patients with advanced non-small-cell lung cancer (NSCLC) treated with immunotherapy.

This scoping review included RCTs and observational studies that measured PFS in advanced NSCLC patients treated with immunotherapy. ASReview, an open-source artificial intelligence-assisted tool, was used to screen and prioritize relevant studies from records identified from PubMed and Embase between 2012 and 2023. Information on study characteristics, PFS definitions, and measurements was extracted.

Forty RCTs and 144 observational studies were included. Most RCTs were conducted across multiple continents (70%), while most observational studies were conducted in Asia (62%). In contrast to RCTs, many observational studies lacked reporting on the end date of PFS measurement (69%), the type of radiological imaging (59%), and the imaging reviewer (78%). For observational studies that did report on PFS definitions and measurements, these often differed from those in RCTs, particularly regarding event definitions, the start and stop dates for PFS measurement, and tumor assessment schedules.

In contrast to RCTs, observational studies often lack reporting on PFS definitions and measurements, and if reported, they differ across observational studies and between them and RCTs. Since observational studies are important for complementing evidence, aligning PFS definition and measurement criteria with those used in RCTs, along with detailed reporting, is needed. However, some variability in PFS measurement characteristics is unavoidable, and therefore, PFS estimates from observational studies should be interpreted critically and carefully.

•Comparing PFS across observational studies (OBSs) and with RCTs is challenging.•We examine how PFS is defined, measured, and reported in RCTs and OBSs.•In contrast to RCTs, OBSs often lack reporting on PFS definitions and measurements.•If reported, the PFS definitions and measurements differ across OBSs and between RCTs.•Aligning PFS characteristics from OBSs with RCTs and detailed reporting are needed.

Comparing PFS across observational studies (OBSs) and with RCTs is challenging.

We examine how PFS is defined, measured, and reported in RCTs and OBSs.

In contrast to RCTs, OBSs often lack reporting on PFS definitions and measurements.

If reported, the PFS definitions and measurements differ across OBSs and between RCTs.

Aligning PFS characteristics from OBSs with RCTs and detailed reporting are needed.