Association between incremental gains in the objective response rate and survival improvement in phase III trials of first-line chemotherapy for extensive disease small-cell lung cancer
| Autor: | Masahiro Tabata, Yoshiro Fujiwara, Katsuyuki Kiura, Nagio Takigawa, Katsuyuki Hotta, Isao Oze, Mitsune Tanimoto, Nobuaki Ochi |
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| Rok vydání: | 2009 |
| Předmět: |
Oncology
medicine.medical_specialty Lung Neoplasms Time Factors medicine.medical_treatment Internal medicine Antineoplastic Combined Chemotherapy Protocols Humans Medicine Lung cancer Survival analysis Randomized Controlled Trials as Topic business.industry Surrogate endpoint Cancer Hematology medicine.disease Small Cell Lung Carcinoma Survival Analysis Chemotherapy regimen Surgery Clinical trial Radiation therapy Treatment Outcome Clinical Trials Phase III as Topic Research Design Linear Models Radiotherapy Adjuvant Cranial Irradiation Prophylactic cranial irradiation business |
| Zdroj: | Annals of Oncology. 20:829-834 |
| ISSN: | 0923-7534 |
| Popis: | Background The duration of, resources required for and cost of clinical trials could be reduced if a surrogate end point was to be used in place of survival. We assessed the extent to which the objective response rate (ORR) is predictive of mortality, how much difference in the ORR is needed to predict an obvious survival difference and what factors could affect the association between the two parameters during the first-line treatment of extensive disease (ED)-small-cell lung cancer (SCLC). Methods We used the ORRs and median survival times (MSTs) from 48 phase III trials of first-line chemotherapy involving 8779 randomised patients with ED-SCLC in a linear regression analysis. The MST difference was calculated as the difference in MST between the investigational and reference arms; the ORR difference was similarly defined. Results ORR difference between the treatment arms was modestly associated with the MST difference in the overall trials (R2 = 0.3314). In contrast, the relationship was stronger among only trials in which prophylactic cranial irradiation was given to those having an objective response to the initial chemotherapy (R2 = 0.6279). In this trial setting, large differences in ORR were needed to predict a survival advantage (1.2-day survival advantage per 2% increase in ORR). Conclusions In the first-line treatment of ED-SCLC, a favourable relationship was detected between the two parameters in the selected trial setting. Large ORR differences were needed to predict a survival benefit, clearly suggesting the need for new chemotherapeutic agents. |
| Databáze: | OpenAIRE |
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