Evaluation of Pancreatic Cancer Clinical Trials and Benchmarks for Clinically Meaningful Future Trials: A Systematic Review.
JAMA Oncol
; 2(9): 1209-16, 2016 Sep 01.
Article
em En
| MEDLINE
| ID: mdl-27270617
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 13â¯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 11â¯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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias Pancreáticas
/
Adenocarcinoma
/
Ensaios Clínicos Fase III como Assunto
/
Ensaios Clínicos Fase II como Assunto
/
Benchmarking
/
Antineoplásicos
Tipo de estudo:
Prognostic_studies
/
Systematic_reviews
Limite:
Humans
Idioma:
En
Revista:
JAMA Oncol
Ano de publicação:
2016
Tipo de documento:
Article