Progressive disease rate as a surrogate endpoint of phase II trials for non-small-cell lung cancer.
BACKGROUND
Although the potential activity of anticancer agents has been traditionally assessed by the response rate (RR) in phase II trials, there is an increasing need to identify alternative endpoints to evaluate the efficacy of novel types of antineoplastic agents such as cytostatic agents. However, none of the proposed alternatives have been validated.


METHODS
RR, rate of progressive disease (PD), and median survival time (MST) were obtained from 44 treatment arms in 42 single-agent phase II trials for non-small-cell lung cancer (NSCLC). Correlations between these parameters and their significance in selection of promising drugs were evaluated.


RESULTS
The median (range) RR and PD rate per treatment arm were 17% (0%-40%) and 41% (8%-93%), respectively. The PD rate correlated more closely with MST (correlation coefficient (r) = 0.80, P < 0.001) than did the RR (r = 0.62, P < 0.001). The RR of active agents against NSCLC ranged broadly from 7% to 40%, whereas their PD rates were all 50% or less. In addition, all treatment arms with a PD rate over 50% had a poor MST of six months or shorter.


CONCLUSIONS
The PD rate was potentially as good an endpoint as RR, and it may be a good candidate for the primary endpoint of phase II trials for novel types of anticancer agents.
Sekine
I
I
Internal Medicine & Thoracic Oncology Division, National Cancer Center Hospital, Tokyo, Japan. isekine@gan2.ncc.go.jp
Tamura
T
T
Kunitoh
H
H
Kubota
K
K
Shinkai
T
T
Kamiya
Y
Y
Saijo
N
N
D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology; D017322:Clinical Trials, Phase II as Topic; D018450:Disease Progression; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D017063:Outcome Assessment, Health Care; D012107:Research Design; D016019:Survival Analysis; D016896:Treatment Outcome