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Cited by 73Pancreatic and Hepatic Oncology ResearchStatistical Methods in Clinical TrialsPancreatitis Pathology and Treatment

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

Rahib, Lola, Fleshman, Julie M., Matrisian, Lynn M., Berlin, Jordan D.·2016·JAMA Oncology
DOI 10.1001/jamaoncol.2016.0585
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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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Crossref · 10.1001/jamaoncol.2016.0585

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  • Newer spatial profiling platforms have advanced toward true single-cell and subcellular resolution.

    “Recent advances in spatial profiling technologies have also allowed the newer platforms to approach true single cell, and even subcellular, resolution280.”

    From Pancreatic cancer: Advances and challenges (2023) · cites this paper as [280]

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Authors
Rahib, L., Fleshman, J. M., Matrisian, L. M., & Berlin, J. D.
Affiliations
  • Pancreatic Cancer Action Network (US)
  • Vanderbilt University (US)
ORCID
Venue
JAMA Oncology
Publisher
American Medical Association (AMA)
Published
2016-09-01
Volume
2
Issue
9
Pages
1209
ISSN
2374-2437 (ISSN-L)
DOI
10.1001/jamaoncol.2016.0585
OpenAlex
W2414965726
Cited by
73
References
79
Citations by year
2026: 3 · 2025: 3 · 2024: 8 · 2023: 7 · 2022: 9 · 2021: 9 · 2020: 4 · 2019: 9 · 2018: 14 · 2017: 7
FWCI
5.39
Type
journal article
Language
en
Open access
closed
Locations
  • JAMA Oncology (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Oncology › Pancreatic and Hepatic Oncology Research
  • Physical Sciences › Mathematics › Statistics and Probability › Statistical Methods in Clinical Trials
  • Health Sciences › Medicine › Surgery › Pancreatitis Pathology and Treatment
Keywords
pancreatic ductal adenocarcinoma, clinical trial failure, overall survival, progression-free survival, gemcitabine, chemotherapy-naive patients, trial design
MeSH terms
Adenocarcinoma, Antineoplastic Agents, Clinical Trials as Topic, Humans, Pancreatic Neoplasms, Survival Rate, Clinical Trials, Phase II as Topic, Clinical Trials, Phase III as Topic, Disease-Free Survival, Benchmarking

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