title: Surrogate End Points for Overall Survival in Loco-Regionally Advanced Nasopharyngeal Carcinoma: An Individual Patient Data Meta-analysis.
abstract: Our objective was to evaluate progression-free survival (PFS) and distant metastasis-free survival (DMFS) as surrogate end points for overall survival (OS) in randomized trials of chemotherapy in loco-regionally advanced nasopharyngeal carcinomas (NPCs).
  
  
  
  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 = 5144 patients). Surrogacy was evaluated at the individual level using a rank correlation coefficient ρ and at the trial level using a correlation coefficient R2between treatment effects on the surrogate end point and OS. A sensitivity analysis was performed with two-year PFS/DMFS and five-year OS.
  
  
  
  PFS was strongly correlated with OS at the individual level (ρ = 0.93, 95% confidence interval [CI] = 0.93 to 0.94) and at the trial level (R2= 0.95, 95% CI = 0.47 to 1.00). For DMFS, too, the individual-level correlation with OS was strong (ρ = 0.98, 95% CI = 0.98 to 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 to 0.99). In the sensitivity analysis, two-year PFS was highly correlated with five-year OS at the individual level (ρ = 0.89, 95% CI = 0.88 to 0.90) and at the trial level (R2= 0.85, 95% CI = 0.46 to 1.00); two-year DMFS was highly correlated with five-year OS at the individual level (ρ = 0.95, 95% CI = 0.94 to 0.95) and at the trial level (R2= 0.78, 95% CI = 0.33 to 1.00).
  
  
  
  PFS and DMFS are valid surrogate end points for OS to assess treatment effect of chemotherapy in loco-regionally advanced NPC, while PFS can be measured earlier.
authors.affiliation: Service de Biostatistique et d'Epidémiologie, Gustave Roussy Cancer Campus, Villejuif, France.|INSERM U1018, CESP, Université Paris-Sud, Université Paris-Saclay, Villejuif, France.|Ligue Nationale Contre le Cancer Meta-Analysis Platform, Gustave Roussy Cancer Campus, Villejuif, France.
authors.forename: Federico
authors.initials: F
authors.lastname: Rotolo
authors.affiliation: Service de Biostatistique et d'Epidémiologie, Gustave Roussy Cancer Campus, Villejuif, France.|INSERM U1018, CESP, Université Paris-Sud, Université Paris-Saclay, Villejuif, France.|Ligue Nationale Contre le Cancer Meta-Analysis Platform, Gustave Roussy Cancer Campus, Villejuif, France.
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Pignon
authors.affiliation: Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
authors.forename: Jean
authors.initials: J
authors.lastname: Bourhis
authors.affiliation: Service de Biostatistique et d'Epidémiologie, Gustave Roussy Cancer Campus, Villejuif, France.|INSERM U1018, CESP, Université Paris-Sud, Université Paris-Saclay, Villejuif, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Marguet
authors.affiliation: Service de Biostatistique et d'Epidémiologie, Gustave Roussy Cancer Campus, Villejuif, France.|Ligue Nationale Contre le Cancer Meta-Analysis Platform, Gustave Roussy Cancer Campus, Villejuif, France.
authors.forename: Julie
authors.initials: J
authors.lastname: Leclercq
authors.affiliation: Pamela Youde Nethersole Eastern Hospital, Hong Kong, China.
authors.forename: Wai
authors.initials: W
authors.lastname: Tong Ng
authors.affiliation: State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, P. R. China.
authors.forename: Jun
authors.initials: J
authors.lastname: Ma
authors.affiliation: Sir YK Pao Centre for Cancer, The Chinese University of Hong Kong, Hong Kong, China.
authors.forename: Anthony T C
authors.initials: AT
authors.lastname: Chan
authors.affiliation: State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, P. R. China.
authors.forename: Pei-Yu
authors.initials: PY
authors.lastname: Huang
authors.affiliation: Shanghai Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, P. R. China.
authors.forename: Guopei
authors.initials: G
authors.lastname: Zhu
authors.affiliation: Hong Kong Sanatorium and Hospital, Hong Kong, China.
authors.forename: Daniel T T
authors.initials: DT
authors.lastname: Chua
authors.affiliation: State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, P. R. China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Sun Yat-Sen University Cancer Center, Guangzhou, P. R. China.
authors.forename: Hai-Qiang
authors.initials: HQ
authors.lastname: Mai
authors.affiliation: Queen Mary Hospital, Hong Kong, China.
authors.forename: Dora L W
authors.initials: DL
authors.lastname: Kwong
authors.affiliation: National Cancer Centre, Singapore, Singapore.
authors.forename: Yoke Lim
authors.initials: YL
authors.lastname: Soong
authors.affiliation: SWOG Statistical Center, Seattle, WA, USA.
authors.forename: James
authors.initials: J
authors.lastname: Moon
authors.affiliation: Tuen Mun. Hospital Hong Kong, China
authors.forename: Yuk
authors.initials: Y
authors.lastname: Tung
authors.affiliation: Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan.
authors.forename: Kwan-Hwa
authors.initials: KH
authors.lastname: Chi
authors.affiliation: Aristotle University of Thessaloniki School of Medicine, Thessaloniki, Greece.
authors.forename: George
authors.initials: G
authors.lastname: Fountzilas
authors.affiliation: Sun Yat-Sen University Cancer Center, Guangzhou, P. R. China.
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Sir YK Pao Centre for Cancer, The Chinese University of Hong Kong, Hong Kong, China.
authors.forename: Edwin Pun
authors.initials: EP
authors.lastname: Hui
authors.affiliation: Pamela Youde Nethersole Eastern Hospital, Hong Kong, China.
authors.forename: Anne W M
authors.initials: AW
authors.lastname: Lee
authors.affiliation: Service de Biostatistique et d'Epidémiologie, Gustave Roussy Cancer Campus, Villejuif, France.|INSERM U1018, CESP, Université Paris-Sud, Université Paris-Saclay, Villejuif, France.|Department of Radiation Therapy, Gustave Roussy, Villejuif, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Blanchard
authors.affiliation: Service de Biostatistique et d'Epidémiologie, Gustave Roussy Cancer Campus, Villejuif, France.|INSERM U1018, CESP, Université Paris-Sud, Université Paris-Saclay, Villejuif, France.|Ligue Nationale Contre le Cancer Meta-Analysis Platform, Gustave Roussy Cancer Campus, Villejuif, France.
authors.forename: Stefan
authors.initials: S
authors.lastname: Michiels
mesh_terms: D014408:Biomarkers, Tumor; D002277:Carcinoma / Q000188:drug therapy* / Q000556:secondary*; D018572:Disease-Free Survival; D006801:Humans; D009303:Nasopharyngeal Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D009362:Neoplasm Metastasis; D016032:Randomized Controlled Trials as Topic; D015996:Survival Rate
chemical_list: D014408:Biomarkers, Tumor