The validity of progression-free survival 2 as a surrogate trial end point for overall survival.
Cancer
; 128(7): 1449-1457, 2022 04 01.
Article
em En
| MEDLINE
| ID: mdl-34985773
ABSTRACT
BACKGROUND:
Overall survival (OS) is the gold-standard end point for oncology trials. However, the availability of multiple therapeutic options after progression and crossover to receive investigational agents confound and delay OS data maturation. Progression-free survival 2 (PFS-2), defined as the time from randomization to progression on first subsequent therapy, has been proposed as a surrogate for OS. Using a meta-analytic approach, the authors aimed to assess the association between OS and PFS-2 and compare this with progression-free survival 1 (PFS-1) and the objective response rate (ORR).METHODS:
An electronic literature search was performed to identify randomized trials of systemic therapies in advanced solid tumors that reported PFS-2 as a prespecified end point. Correlations between OS and PFS-2, OS and PFS-1, and OS and ORR as hazard ratios (HRs) or odds ratios (ORs) were assessed via linear regression weighted by trial size.RESULTS:
Thirty-eight trials were included, and they comprised 19,031 patients across 8 tumor types. PFS-2 displayed a moderate correlation with OS (r = 0.67; 95% confidence interval [CI], 0.08-0.69). Conversely, correlations of ORR (r = 0.12; 95% CI, 0.00-0.13) and PFS-1 (r = 0.21; 95% CI, 0.00-0.33) were poor. The findings for PFS-2 were consistent for subgroup analyses by treatment type (immunotherapy vs nonimmunotherapy r = 0.67 vs 0.67), survival post progression (<12 vs ≥12 months r = 0.86 vs 0.79), and percentage not receiving subsequent treatment (<50% vs ≥50% r = 0.70 vs 0.63).CONCLUSIONS:
Across diverse tumors and therapies, the treatment effect on PFS-2 correlated moderately with the treatment effect on OS. PFS-2 performed consistently better than PFS-1 and ORR, regardless of postprogression treatment and postprogression survival. PFS-2 should be included as a key trial end point in future randomized trials of solid tumors.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias
Tipo de estudo:
Clinical_trials
/
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
Cancer
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
Austrália