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Review
September 2016

Evaluation of Pancreatic Cancer Clinical Trials and Benchmarks for Clinically Meaningful Future TrialsA Systematic Review

Author Affiliations
  • 1Pancreatic Cancer Action Network, Manhattan Beach, California
  • 2Vanderbilt-Ingram Cancer Center, Vanderbilt University, Nashville, Tennessee
 

Copyright 2016 American Medical Association. All Rights Reserved. Applicable FARS/DFARS Restrictions Apply to Government Use.

JAMA Oncol. 2016;2(9):1209-1216. doi:10.1001/jamaoncol.2016.0585
Abstract

Importance  Progress in the treatment of pancreatic adenocarcinoma has been minimal; it remains the only major cancer type with a 5-year survival rate of less than 10%.

Objective  To explore why a large proportion of advanced pancreatic cancer clinical trials executed over the past 25 years have had negative results and to identify benchmarks that could have predicted success.

Evidence Review  Phase 3 studies of patients with advanced pancreatic cancer were identified by searching clinicaltrials.gov and the scientific literature.

Findings  Thirty-two phase 3 studies in 13 675 chemotherapy-naive patients resulted in 3 agents or combinations being considered clinically meaningful. Nineteen agents or combinations (70%) were tested in phase 2 trials preceding the phase 3 trial. In cases with paired phase 2 and 3 results, meeting the primary end point of the phase 2 trial predicted the outcome of the phase 3 trial 76% of the time but proceeded despite phase 2 negative results in 10 cases. We applied criteria for a clinically meaningful result identified by the American Society of Clinical Oncology (ASCO) Cancer Research Committee to these historical cases. Overall, progression-free and 1-year survival of experimental arms was compared with time period–controlled median values of control arms to normalize for the observed increase in response to gemcitabine over time.

Conclusions and Relevance  Applying the benchmark of a 50% improvement in overall survival as the primary end point to phase 2 data, or secondary end points of a 90% increase in 1-year survival or an 80% to 100% increase in progression-free survival, showed the greatest ability to predict a clinically meaningful phase 3 trial. Had these criteria been applied to these trials over the past 25 years, more than 11 571 patients enrolled in phase 3 trials that did not meet the primary end point could theoretically have been diverted to earlier-stage trials in an attempt to more rapidly advance the field.

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