951O - Surrogate endpoints for overall survival in loco-regionally advanced nasopharyngeal carcinoma: Results from the individual patient data meta-analys...

Date 10 October 2016
Event ESMO 2016 Congress
Session Head and neck cancers
Topics Head and Neck Cancers
Presenter Federico Rotolo
Citation Annals of Oncology (2016) 27 (6): 328-350. 10.1093/annonc/mdw376
Authors F. Rotolo1, J. Pignon1, S. Marguet2, J. Ma3, A.T.C. Chan4, P. Huang3, G. Zhu5, D.T. Chua6, Y. Chen3, H. Mai3, D.W. Kwong7, Y.L. Soong8, J. Moon9, Y. Tung10, K. Chi11, G. Fountzilas12, L. Zhang3, A. Lee13, P. Blanchard14, S. Michiels1
  • 1Service De Biostatistique Et D’epidemiologie, Cesp, Inserm U1018, Univ. Paris Sud, Univ. Paris-saclay, Ligue Contre Le Cancer, Gustave Roussy Cancer Campus, FR-94805 - Villejuif/FR
  • 2Service De Biostatistique Et D’epidemiologie, Gustave Roussy Cancer Campus, FR-94805 - Villejuif/FR
  • 3State Key Laboratory Of Oncology In South China, Sun Yat-sen University Cancer Center, Guangzhou/CN
  • 4Sir Yk Pao Centre For Cancer, The Chinese University of Hong Kong, Hong Kong/HK
  • 5Shanghai Ninth People's Hospital, Shanghai Jiaotong Univerisity School of Medicine, Shanghai/CN
  • 6Department Of Radiotherapy, Hong Kong Sanatorium & Hospital, Hong Kong/HK
  • 7Department Of Clinical Oncology, Queen Mary Hospital, Hong Kong/HK
  • 8Division Of Radiation Oncology, National Cancer Center, Singapore/SG
  • 9Swog Statistical Center, Fred Hutchinson Cancer Research Center, Seattle/US
  • 10Department Of Clinical Oncology, Tuen Mun Hospital, Hong Kong/HK
  • 11Department Of Radiation Therapy And Oncology, Shin Kong Wu Ho-Su Memorial Hospital, Taipei/TW
  • 12Medical Oncology Clinic, Papageorgiou Hospital Aristotle University of Thessaloniki, 564 29 - Thessaloniki/GR
  • 13Department Of Clinical Oncology, Pamela Youde Nethersole Eastern Hospital, Hong Kong/HK
  • 14Department Of Radiation Therapy, Gustave Roussy Cancer Campus, FR-94805 - Villejuif/FR



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.