Time to progression as a surrogate marker for overall survival in patients with advanced non-small cell lung cancer.
OBJECTIVE
With the increasing number of active compounds available for advanced non-small cell lung cancer, it is useful to evaluate whether surrogate end points can replace survival in randomized trials for the rapid and efficient assessment of efficacy. We examined the association between differences in overall survival and time to progression (TTP) using a literature survey.


METHODS
We used median TTP (MTTP) and median survival time (MST) from 54 phase III trials of first-line chemotherapy involving 23,457 advanced non-small cell lung cancer patients in a multiple linear regression analysis. The MST ratio in each trial was defined as the ratio of MST in the investigational arm to that in the reference arm. The MTTP ratio was defined similarly.


RESULTS
The degree of the association between the MST and MTTP ratios was only moderate both in the overall cohort (R(2) = 0.33) and various trial settings (R(2) = 0.16-0.51), although the MTTP ratio was an independent factor influencing the MST ratio in the multiple regression model (p < 0.01). This means that the MTTP ratio could account for less than half of the variance in the MST ratio.


CONCLUSIONS
The TTP potentially acts as a surrogate marker, but may not be still a definitive alternative in the first-line setting.
Hotta
Katsuyuki
K
Department of Respiratory Medicine, Okayama University Hospital, Okayama, Japan. khotta@md.okayama-u.ac.jp
Fujiwara
Yoshiro
Y
Matsuo
Keitaro
K
Kiura
Katsuyuki
K
Takigawa
Nagio
N
Tabata
Masahiro
M
Tanimoto
Mitsune
M
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D015415:Biomarkers / Q000032:analysis*; D014408:Biomarkers, Tumor / Q000032:analysis; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000401:mortality* / Q000473:pathology; D002423:Cause of Death; D017326:Clinical Trials, Phase III as Topic; D018450:Disease Progression; D005260:Female; D006801:Humans; D016014:Linear Models; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality* / Q000473:pathology; D008297:Male; D015999:Multivariate Analysis; D009367:Neoplasm Staging; D011336:Probability; D012680:Sensitivity and Specificity; D016019:Survival Analysis; D013997:Time Factors
D015415:Biomarkers; D014408:Biomarkers, Tumor