Proportion of Patients in Phase 1 Oncology Trials Receiving Treatments that are Ultimately Approved
Menée à partir d'une revue systématique de la littérature publiée jusqu'en juillet 2018, cette étude estime en cancérologie la proportion de patients ayant reçu, dans le cadre d'un essai de phase I, un traitement anticancéreux pour lequel l'indication et la dose administrée seront autorisées par la "U.S. Food and Drug Administration" ou recommandées par le "National Comprehensive Cancer Network"
Résumé en anglais
Background : Phase 1 oncology trials are often regarded as a therapeutic option for patients. However, such claims have relied on surrogate measures of benefit, such as objective response.
Methods : Using a systematic search of publications, we assessed the therapeutic value of phase 1 cancer trial participation by determining the probability that patients will receive active doses of treatments that eventually receive FDA approval or an NCCN guideline recommendation for their indication. ClinicalTrials.gov, Pubmed, ASCO reports, NCCN Guidelines and Drugs@FDA were searched between May 1, 2018 and July 31, 2018. All statistical tests were two-sided.
Results : 1000 phase 1 oncology trials initiated between 2005 and 2010 and enrolling 32,582 patients were randomly sampled from 3229 eligible trials on ClinicalTrials.gov. A total of 386 (1.2%) patients received a treatment that was approved by the U.S. Food and Drug Administration for their malignancy at a dose delivered in the trial; including NCCN guideline recommendations, the number and proportion are 1168 (3.6%). Meta regression showed a statistically significantly greater proportion of patients receiving a drug that was ultimately FDA approved in biomarker trials (rate ratio = 4.49, 95%CI = 1.53 to 13.23, p = 0.006) and single-indication trials (rate ratio = 3.32, [1.21 – 9.15], p = 0.02; proportions were significantly lower for combination vs. monotherapy trials (rate ratio = 0.09, [0.01 – 0.68], p = 0.02).
Conclusions : One in 83 patients in phase 1 cancer trials received a treatment that was approved for their indication at the doses received. Given published estimates of serious adverse event rates of 10-19%, this represents low therapeutic value for phase 1 trial participation.
