Surrogate endpoints for overall survival in loco-regionally advanced nasopharyngeal carcinoma: Results from the individual patient data meta-analysis MAC-NPC2

Date

10 Oct 2016

Session

Head and neck cancers

Presenters

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

Author affiliations

  • 1 Service 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
  • 2 Service De Biostatistique Et D’epidemiologie, Gustave Roussy Cancer Campus, FR-94805 - Villejuif/FR
  • 3 State Key Laboratory Of Oncology In South China, Sun Yat-sen University Cancer Center, Guangzhou/CN
  • 4 Sir Yk Pao Centre For Cancer, The Chinese University of Hong Kong, Hong Kong/HK
  • 5 Shanghai Ninth People's Hospital, Shanghai Jiaotong Univerisity School of Medicine, Shanghai/CN
  • 6 Department Of Radiotherapy, Hong Kong Sanatorium & Hospital, Hong Kong/HK
  • 7 Department Of Clinical Oncology, Queen Mary Hospital, Hong Kong/HK
  • 8 Division Of Radiation Oncology, National Cancer Center, Singapore/SG
  • 9 Swog Statistical Center, Fred Hutchinson Cancer Research Center, Seattle/US
  • 10 Department Of Clinical Oncology, Tuen Mun Hospital, Hong Kong/HK
  • 11 Department Of Radiation Therapy And Oncology, Shin Kong Wu Ho-Su Memorial Hospital, Taipei/TW
  • 12 Medical Oncology Clinic, Papageorgiou Hospital Aristotle University of Thessaloniki, 564 29 - Thessaloniki/GR
  • 13 Department Of Clinical Oncology, Pamela Youde Nethersole Eastern Hospital, Hong Kong/HK
  • 14 Department Of Radiation Therapy, Gustave Roussy Cancer Campus, FR-94805 - Villejuif/FR
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Background

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).

Methods

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.

Results

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).

Conclusions

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

Funding

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).

Disclosure

All authors have declared no conflicts of interest.

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