Surrogate endpoints for overall survival in locally advanced head and neck cancer: meta-analyses of individual patient data

Stefan Michiels ¹, Aurélie Le Maître , Marc Buyse

⁰Department of Biostatistics and Epidemiology, Institut Gustave Roussy, Villejuif, France.

The Lancet. Oncology +

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February 28, 2009

View abstract on PubMed

Summary

Event-free survival (EFS) is a better surrogate endpoint than locoregional control for estimating treatment effects on overall survival in head and neck cancer trials. This finding can accelerate the development of new cancer therapies.

Area Of Science

Oncology
Clinical Trials
Radiotherapy and Chemotherapy

Background

Head and neck squamous-cell carcinoma (HNSCC) trials typically use overall survival as the gold standard endpoint.
Current trial durations and costs necessitate exploring alternative surrogate endpoints.
Locoregional control and event-free survival (EFS) are potential surrogates for overall survival.

Purpose Of The Study

To evaluate if duration of locoregional control or EFS can serve as surrogate endpoints for overall survival in locally advanced HNSCC.
To determine if these surrogates can reduce the time and cost associated with developing new cancer treatments.

Main Methods

Individual patient data from 104 trials (22,744 patients) across four meta-analyses were analyzed.
Rank correlation coefficients assessed surrogacy at the individual patient level.
Correlation coefficients (R) evaluated treatment effects at the trial level.

Main Results

Overall survival showed stronger individual-level correlation with EFS (0.82-0.90) than locoregional control (0.65-0.76).
Treatment effects on EFS strongly correlated with overall survival for radiotherapy (R=0.98) and chemotherapy (R=0.79-0.93).
Locoregional control showed weaker correlations with overall survival for both radiotherapy (R=0.94) and chemotherapy (R=0.53-0.84).

Conclusions

Event-free survival (EFS) is a more robust correlate of overall survival compared to locoregional control.
EFS can be utilized as a surrogate endpoint in randomized trials for locally advanced HNSCC.
Using EFS can facilitate more efficient assessment of radiotherapy and chemotherapy treatment effects.

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