Dataset Information

Applying State-of-the-Art Survival Extrapolation Techniques to the Evaluation of CAR-T Therapies: Evidence from a Systematic Literature Review.

ABSTRACT:

Introduction

Traditional statistical techniques for extrapolating short-term survival data for anticancer therapies assume the same mortality rate for noncured and "cured" patients, which is appropriate for projecting survival of non-curative therapies but may lead to an underestimation of the treatment effectiveness for potentially curative therapies. Our objective was to ascertain research trends in survival extrapolation techniques used to project the survival benefits of chimeric antigen receptor T cell (CAR-T) therapies.

Methods

A global systematic literature search produced a review of survival analyses of CAR-T therapies, published between January 1, 2015 and December 14, 2020, based on publications sourced from MEDLINE, scientific conferences, and health technology assessment agencies. Trends in survival extrapolation techniques used, and the rationale for selecting advanced techniques, are discussed.

Results

Twenty publications were included, the majority of which (65%, N = 13) accounted for curative intent of CAR-T therapies through the use of advanced extrapolation techniques, i.e., mixture cure models [MCMs] (N = 10) or spline-based models (N = 3). The authors' rationale for using the MCM approach included (a) better statistical fits to the observed Kaplan-Meier curves (KMs) and (b) visual inspection of the KMs indicated that a proportion of patients experienced long-term remission and survival which is not inherently captured in standard parametric distributions.

Discussion

Our findings suggest that an advanced extrapolation technique should be considered in base case survival analyses of CAR-T therapies when extrapolating short-term survival data to long-term horizons extending beyond the clinical trial duration.

Conclusion

Advanced extrapolation techniques allow researchers to account for the proportion of patients with an observed plateau in survival from clinical trial data; by only using standard-partitioned modeling, researchers may risk underestimating the survival benefits for the subset of patients with long-term remission. Sensitivity analysis with an alternative advanced extrapolation technique should be implemented and re-assessment using clinical trial extension data and/or real-world data should be conducted as longer-term data become available.

SUBMITTER: Sussman M

PROVIDER: S-EPMC8342396 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:BackgroundAdvances in targeted therapy development and tumor sequencing technology are reclassifying cancers into smaller biomarker-defined diseases. Randomized controlled trials (RCTs) are often impractical in rare diseases, leading to calls for single-arm studies to be sufficient to inform clinical practice based on a strong biological rationale. However, without RCTs, favorable outcomes are often attributed to therapy but may be due to a more indolent disease course or other biases. When the clinical benefit of targeted therapy in a common cancer is established in RCTs, this benefit may extend to rarer cancers sharing the same biomarker. However, careful consideration of the appropriateness of extending the existing trial evidence beyond specific cancer types is required. A framework for extrapolating evidence for biomarker-targeted therapies to rare cancers is needed to support transparent decision-making.ObjectivesTo construct a framework outlining the breadth of criteria essential for extrapolating evidence for a biomarker-targeted therapy generated from RCTs in common cancers to different rare cancers sharing the same biomarker.DesignA series of questions articulating essential criteria for extrapolation.MethodsThe framework was developed from the core topics for extrapolation identified from a previous scoping review of methodological guidance. Principles for extrapolation outlined in guidance documents from the European Medicines Agency, the US Food and Drug Administration, and Australia's Medical Services Advisory Committee were incorporated.ResultsWe propose a framework for assessing key assumptions of similarity of the disease and treatment outcomes between the common and rare cancer for five essential components: prognosis of the biomarker-defined cancer, biomarker test analytical validity, biomarker actionability, treatment efficacy, and safety. Knowledge gaps identified can be used to prioritize future studies.ConclusionThis framework will allow systematic assessment, standardize regulatory, reimbursement and clinical decision-making, and facilitate transparent discussions between key stakeholders in drug assessment for rare biomarker-defined cancers.