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2,109 randomized oncology trials map continuous, meager improvements in progression-free and overall survival over 50

Austin J Parish1, Ioana Alina Cristea2, Ewoud Schuit3

  • 1Meta-Research Innovation Center at Stanford (METRICS), Stanford University, Stanford, CA, USA; Department of Emergency Medicine, Lincoln Medical and Mental Health Center, Weill Cornell Medicine of Cornell University, Bronx, NY, USA.

Journal of Clinical Epidemiology
|July 1, 2022
PubMed
Abstract

Insights

Oncology research shows steady progress in progression-free survival but limited clinically meaningful improvements in overall survival. Most trials do not meet significant thresholds for extending life.

Area of Science:

  • Oncology
  • Clinical Trials
  • Survival Analysis

Background:

  • Assessing treatment efficacy in oncology is crucial for patient outcomes.
  • Understanding trends in survival benefits over time informs future research directions.

Purpose of the Study:

  • To analyze patterns and time trends in overall survival (OS) and progression-free survival (PFS) treatment effects.
  • To evaluate the clinical meaningfulness of survival improvements in oncology randomized controlled trials (RCTs).

Main Methods:

  • Conducted a systematic search for oncology network meta-analyses (NMAs) up to September 30, 2021.
  • Extracted hazard ratios for systemic treatments from eligible RCTs within NMAs.
  • Explored relationships between treatment effects, publication year, and trial design.

Main Results:

  • Analyzed data from 2,109 unique RCTs across 241 NMAs.
  • Observed average hazard reductions of 12%-14% for OS and 27%-30% for PFS, with significant heterogeneity.
  • Found a modest correlation between OS and PFS treatment effects (r=0.60).
  • Identified a trend of increasing PFS treatment effects over time, while OS effects remained stable.
  • Noted that only 20% of trials met criteria for clinically meaningful OS improvements.
  • Mean absolute improvements were 1.6 months for PFS and 1.4 months for OS in a subset of trials.

Conclusions:

  • Oncology research demonstrates continuous progress over 50 years.
  • However, few studies achieve clinically meaningful improvements in overall survival.
  • Further advancements are needed to translate survival gains into substantial patient benefit.
Keywords:
CancerClinical trial designMeta-ResearchNetwork meta-analysisOncologyOverall survivalProgression free survivalRandomized trialUmbrella review

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