Elucidation of relationship between tumor size and survival in non-small-cell lung cancer patients can aid early decision making in clinical drug development.
Four non-small-cell lung cancer (NSCLC) registration trials were utilized to develop models linking survival to risk factors and changes in tumor size during treatment. The purpose was to leverage existing quantitative knowledge to facilitate future development of anti-NSCLC drugs. Eleven risk factors were screened using a Cox model. A mixed exponential decay and linear growth model was utilized for modeling tumor size. Survival times were described in a parametric model. Eastern Cooperative Oncology Group (ECOG) score and baseline tumor size were consistent prognostic factors of survival. Tumor size was well described by the mixed model. The parametric survival model includes ECOG score, baseline tumor size, and week 8 tumor size change as predictors of survival duration. The change in tumor size at week 8 allows early assessment of the activity of an experimental regimen. The survival model and the tumor model will be beneficial for early screening of candidate drugs, simulating NSCLC trials, and optimizing trial designs.
Division of Pharmacometrics, Office of Clinical Pharmacology, US Food and Drug Administration, Silver Spring, Maryland, USA. yaning.wang@fda.hhs.gov
Y
Y
Wang
C
C
Sung
C
C
Dartois
R
R
Ramchandani
B P
BP
Booth
E
E
Rock
J
J
Gobburu
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000401:mortality* / Q000473:pathology*; D003657:Decision Making; D015195:Drug Design; D015507:Drugs, Investigational; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000401:mortality* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D015233:Models, Statistical; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D012307:Risk Factors; D016019:Survival Analysis; D013997:Time Factors
D000970:Antineoplastic Agents; D015507:Drugs, Investigational