Our objective was to evaluate progression-free survival (PFS) and distant metastasis-free survival (DMFS) as surrogate endpoints for overall survival (OS) in randomized trials of chemotherapy in loco-regionally advanced nasopharyngeal carcinomas (LANPC).
Individual patient data were obtained from 19 trials of the updated Meta-Analysis of Chemotherapy in Nasopharyngeal Carcinoma (MAC-NPC) plus one additional trial (total: 5 144 patients). Surrogacy was evaluated at the individual level using a rank correlation coefficient &rgr; and at the trial level using a correlation coefficient R2 between treatment effects on the surrogate endpoint and OS. A sensitivity analysis was performed with 2-year PFS/DMFS and 5-year OS.
PFS was strongly correlated with OS at the individual level (&rgr; = 0.93, 95% Confidence Interval [CI]: 0.93–0.94) and at the trial level (R2 = 0.95, 95% CI: 0.47–1.00). For DMFS, too, the individual-level correlation with OS was strong (&rgr; = 0.98, 95% CI: 0.98─0.98); at trial level, the correlation was high but the regression adjusted for measurement error could not be computed (unadjusted R2 = 0.96, 95% CI: 0.94─0.99). In the sensitivity analysis, 2-year PFS was highly correlated with 5-year OS at the individual level (&rgr; = 0.89, 95% CI: 0.88–0.90) and at the trial level (R2 = 0.85, 95% CI: 0.46–1.00); 2-year DMFS was highly correlated with 5-year OS at the individual level (&rgr; = 0.95, 95% CI: 0.94–0.95) and r at trial level (R2 = 0.78, 95% CI: 0.33–1.00).
PFS and DMFS are valid surrogate endpoints for OS to assess treatment effect of chemotherapy in LANPC and PFS can be measured earlier.
Clinical trial identification
Legal entity responsible for the study
Meta-Analysis Platform of the 'Ligue Nationale Contre le Cancer', Gustave Roussy Cancer Campus, Villejuif, France
French Ministry of Health (Programme d'actions integrees de recherche VADS) Ligue Nationale Contre le Cancer French National Cancer Institute (SHS 2014-141) National Cancer Institute, National Institutes of Health (CA180888 and CA180819) Hellenic Cooperative Oncology Group (HE R_5G).
All authors have declared no conflicts of interest.