Is response rate increment obtained by molecular targeted agents related to survival benefit in the phase III trials of advanced cancer?
BACKGROUND
It remains unclear whether response rate (RR) is related to survival benefit in phase III trials of advanced cancer treated with molecular targeted agents (MTA) in combination with standard therapies.


METHODS
We carried out a systematic search of PubMed for randomized phase III trials of four solid tumors examining the efficacy of MTA when added to a standard therapy. We examined whether there were any associations between RR increment obtained by the addition of targeted agents (DeltaRR) and survival benefit in phase III trials.


RESULTS
We identified 26 phase III trials of MTA with a total of 21 156 patients and 29 experimental arms of MTA. Studies which showed significant survival benefit had higher DeltaRR compared with those which did not show significant benefit. In the receiver operating characteristic curve analysis, using a 7% gain as threshold value for DeltaRR allowed assessment of survival benefit with high sensitivity and specificity. There were also significant relationships between DeltaRR and hazard ratios for overall survival and progression-free survival in the linear regression analysis.


CONCLUSIONS
RR increment obtained by the addition of MTA to a standard therapy may be useful to predict survival benefit in clinical phase III trials of advanced cancer.
Tsujino
K
K
Department of Respiratory Medicine, Allergy and Rheumatic Diseases, Osaka University Graduate School of Medicine, Suita, Osaka. Electronic address: ktujino@imed3.med.osaka-u.ac.jp.
Shiraishi
J
J
Department of Medical Physics, School of Health Sciences, Kumamoto University, Kumamoto.
Tsuji
T
T
Department of Internal Medicine, National Hospital Organization Kinki-chuo Chest Medical Center, Sakai, Osaka.
Kurata
T
T
Department of Medical Oncology, Kinki University School of Medicine, Osakasayama, Osaka.
Kawaguchi
T
T
Department of Internal Medicine, National Hospital Organization Kinki-chuo Chest Medical Center, Sakai, Osaka.
Kubo
A
A
Division of Respiratory Medicine and Allergology, Department of Internal Medicine, Aichi Medical University School of Medicine, Aichi.
Takada
M
M
Department of Medical Oncology, Sakai Hospital, Kinki University School of Medicine, Sakai, Osaka, Japan.
D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D017326:Clinical Trials, Phase III as Topic; D016503:Drug Delivery Systems; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy*; D016032:Randomized Controlled Trials as Topic; D016019:Survival Analysis
D000970:Antineoplastic Agents