학술논문

Impact of progression at baseline and on-treatment progression events in three large prostate cancer trials.
Document Type
Article
Source
European Journal of Cancer. Jan2020, Vol. 125, p142-152. 11p.
Subject
*CANCER chemotherapy
*CANCER pain
*CLINICAL trials
*CONFIDENCE intervals
*MULTIVARIATE analysis
*PROSTATE tumors
*STATISTICS
*SURVIVAL analysis (Biometry)
*PROSTATE-specific antigen
*DATA analysis
*TREATMENT effectiveness
*PROPORTIONAL hazards models
*RETROSPECTIVE studies
*DISEASE progression
*ODDS ratio
Language
ISSN
0959-8049
Abstract
There is a discussion about the optimal timing to initiate or switch treatment in metastatic castration-resistant prostate cancer (mCRPC). This post hoc analysis of 3 large trials for men with mCRPC examined the influence of the type of progression at initiation of first-line chemotherapy, as well as the type of progression during treatment, on treatment outcomes. Data from the phase III studies VENICE (n = 1224), TAX327 (n = 1006) and FIRSTANA (n = 1168) were used as independent data sets. Type of progression was defined as follows: prostate-specific antigen (PSA) only (group 1), radiological (±PSA) (group 2) or pain (±PSA, ± radiological) progression (group 3). The impact of baseline type of progression on overall survival (OS) was evaluated in multivariate Cox regression analysis with backward elimination, stratified for the Eastern Cooperative Oncology Group performance score and treatment arm. The median OS (arms combined) from treatment initiation in VENICE was 28.6, 26.3 and 16.9 months for G1, G2 and G3, respectively (hazard ratio: 1.14 [95% confidence interval {CI}: 0.92–1.41%] in G2 and 2.13 [95% CI: 1.75–2.59%] in G3 compared with G1). Multivariate analysis (arms combined) showed that pain progression at baseline was an independent predictor of poor OS. Similar findings were observed in the TAX327 and FIRSTANA data sets. During treatment, pain or radiological progression preceded PSA progression in ~55% of the patients. The retrospective characteristic of this study is a limitation. The type of progression at baseline strongly predicts OS in men with mCRPC treated with first-line chemotherapy. During treatment, pain and/or radiological progression preceded PSA progression as the first progression event in ~55% of the patients. This finding has the prospect to be incorporated in clinical guidelines and to be practice changing because it implies the need for regular imaging and not to rely on PSA progression alone. • Type of progression at initiation of chemotherapy impacts survival in mCRPC. • Pain progression at baseline was associated with 1-year shorter overall survival. • Pain and/or radiological progression as first progression event in ~55% of patients. • Baseline characteristics of patients in trials have an impact on trial outcomes. [ABSTRACT FROM AUTHOR]