Abstract 674P
Background
Insufficient patient enrollment per month (=accrual) is the leading cause of cancer trial termination. This study identifies and quantifies factors associated with patient accrual in trials leading to the US Food and Drug Administration (FDA) approval of new cancer drugs.
Methods
All cancer drugs with FDA approval were identified in the Drugs@FDA database (2000-2022). Data on drug indication’s background-, treatment-, disease-, and trial-related factors were collected from FDA labels, clinicaltrials.gov, and the Global Burden of Disease study. The association between patient accrual and collected variables was assessed in Poisson regression models reporting adjusted rate ratios (aRR) for randomized and single-arm trials.
Results
We identified 170 drugs with approval in 455 cancer indications based on 292 randomized and 163 single-arm trials. Among randomized trials, accrual rates were 0.30-times (p<0.001), 0.73-times (p<0.001), and 0.88-times (p=0.361) lower for ultra-rare, rare, and common than non-orphan indications. Accrual was positively associated with disease burden (aRR: 1.0003 per DALY, p<0.001), trial sites (aRR: 1.001 per site, p<0.001), participating countries (aRR: 1.02 per country, p<0.001), and phase 3 vs. 1/2 trials (aRR: 1.64, p=0.037). Enrollment was negatively associated with advanced-line vs. first-line treatments (aRR: 0.81, p=0.010) and monotherapy vs. combination treatments (aRR: 0.80, p=0.007). Accrual was 0.80-times lower (p=0.209) in government-sponsored vs. industry-sponsored trials. Results were consistent for single-arm trials.
Conclusions
Disease incidence and burden alongside the number of study sites and participating countries were significantly associated with patient accrual. For rare disease trials, greater financial incentives could expedite patient enrollment. Novel trial design features, including skewed randomization, crossover, or open-label masking, did not entice patient enrollment.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
621P - Phase II trial of encorafenib and binimetinib (E+B) in patients (pts) with BRAF-altered advanced solid tumors: Results of E+B cohort in the BELIEVE trial (NCCH1901)
Presenter: Yoshitaka Honma
Session: Poster session 01
622P - Safety and efficacy of ifebemtinib (IN10018) combined with D-1553 in solid tumors with KRAS G12C mutation: Results from a phase Ib/II study
Presenter: Zhengbo Song
Session: Poster session 01
624P - Belvarafenib in patients (pts) with BRAF class II or III alteration-positive tumours: TAPISTRY study
Presenter: Rafal Dziadziuszko
Session: Poster session 01
625P - Initial results from the phase I, first-in-human study of the covalent, PI3Kα inhibitor TOS-358 in patients with solid tumors, expressing PI3Kα mutations or amplifications
Presenter: Marwan Fakih
Session: Poster session 01
626P - Roginolisib (IOA-244), a first oral allosteric modulator of phosphoinositide 3-kinase inhibitor delta (PI3Kδ) in patients with metastatic uveal melanoma
Presenter: Anna Di Giacomo
Session: Poster session 01
627P - Long-term efficacy and safety of larotrectinib in non-primary central nervous system (CNS) TRK fusion cancer
Presenter: Alexander Drilon
Session: Poster session 01
628P - Efficacy and safety of larotrectinib as first-line treatment for patients (pts) with TRK fusion cancer: An updated analysis
Presenter: David Hong
Session: Poster session 01
629P - Phase I study of pamiparib and cabozantinib in patients with metastatic solid tumors harboring homologous recombination deficiency (HRD)
Presenter: Siqing Fu
Session: Poster session 01