BACKGROUND: In 2004, docetaxel was shown to prolong the overall survival (OS) of patients with metastatic castration-resistance prostate cancer (mCRPC). Since 2010, five new systemic therapies have been shown to prolong OS in men with mCRPC. We sought to evaluate the aggregate impact of these newer therapies on the OS of patients with mCRPC. METHODS: Two cohorts of patients diagnosed with mCRPC between 2004 and 2007, treated with drugs used in the limited treatment era only (A), and between 2010 and 2013, treated also with newer therapies (B), were identified from the Dana-Farber Cancer Institute database. The analysis endpoint was OS within 5 years after mCRPC diagnosis. Kaplan-Meier method assessed time-to-event distributions with median (95% confidence interval (CI)). A piece-wise regression model assessed the association between endpoint and treatment cohorts with estimate of hazard ratio (HR) with 95% CI within two time segments in univariate and multivariable analyses adjusting for relevant covariates. RESULTS: Compared to cohort A (n = 318), cohort B (n = 272) patients in newer therapy era demonstrated an OS advantage (2.8 vs. 2.2 years) with a 41% decreased risk of death (HR = 0.59; 95% CI, 0.47-0.74; P < 0.0001), and a 3-year OS rate of 46% vs. 33%. This benefit was accentuated (median OS 2.7 vs. 2.1 years; HR = 0.46; 95% CI, 0.32-0.67; P < 0.0001) in patients who initially presented with de-novo metastatic disease (de-novo). On multivariable analysis, longer OS was associated with cohort B vs. A and performance status 0 vs. 1. CONCLUSIONS: Using a single-institution registry, mCRPC patients treated since 2010 had a significant survival improvement vs. those treated before 2010. Although the median survival was only modestly improved and less than predicted when simply adding each newer drug survival advantage, the cumulative benefit from the new therapies was more pronounced in longer-term survivors and de-novo patients.
BACKGROUND: In 2004, docetaxel was shown to prolong the overall survival (OS) of patients with metastatic castration-resistance prostate cancer (mCRPC). Since 2010, five new systemic therapies have been shown to prolong OS in men with mCRPC. We sought to evaluate the aggregate impact of these newer therapies on the OS of patients with mCRPC. METHODS: Two cohorts of patients diagnosed with mCRPC between 2004 and 2007, treated with drugs used in the limited treatment era only (A), and between 2010 and 2013, treated also with newer therapies (B), were identified from the Dana-Farber Cancer Institute database. The analysis endpoint was OS within 5 years after mCRPC diagnosis. Kaplan-Meier method assessed time-to-event distributions with median (95% confidence interval (CI)). A piece-wise regression model assessed the association between endpoint and treatment cohorts with estimate of hazard ratio (HR) with 95% CI within two time segments in univariate and multivariable analyses adjusting for relevant covariates. RESULTS: Compared to cohort A (n = 318), cohort B (n = 272) patients in newer therapy era demonstrated an OS advantage (2.8 vs. 2.2 years) with a 41% decreased risk of death (HR = 0.59; 95% CI, 0.47-0.74; P < 0.0001), and a 3-year OS rate of 46% vs. 33%. This benefit was accentuated (median OS 2.7 vs. 2.1 years; HR = 0.46; 95% CI, 0.32-0.67; P < 0.0001) in patients who initially presented with de-novo metastatic disease (de-novo). On multivariable analysis, longer OS was associated with cohort B vs. A and performance status 0 vs. 1. CONCLUSIONS: Using a single-institution registry, mCRPC patients treated since 2010 had a significant survival improvement vs. those treated before 2010. Although the median survival was only modestly improved and less than predicted when simply adding each newer drug survival advantage, the cumulative benefit from the new therapies was more pronounced in longer-term survivors and de-novo patients.
Authors: Wanling Xie; Meredith M Regan; Marc Buyse; Susan Halabi; Philip W Kantoff; Oliver Sartor; Howard Soule; Donald Berry; Noel Clarke; Laurence Collette; Anthony D'Amico; Richard De Abreu Lourenco; James Dignam; Mario Eisenberger; Nicholas James; Karim Fizazi; Silke Gillessen; Yohann Loriot; Nicolas Mottet; Wendy Parulekar; Howard Sandler; Daniel E Spratt; Matthew R Sydes; Bertrand Tombal; Scott Williams; Christopher J Sweeney Journal: J Clin Oncol Date: 2020-06-18 Impact factor: 44.544
Authors: Hanna Tukachinsky; Russell W Madison; Jon H Chung; Ole V Gjoerup; Eric A Severson; Lucas Dennis; Bernard J Fendler; Samantha Morley; Lei Zhong; Ryon P Graf; Jeffrey S Ross; Brian M Alexander; Wassim Abida; Simon Chowdhury; Charles J Ryan; Karim Fizazi; Tony Golsorkhi; Simon P Watkins; Andrew Simmons; Andrea Loehr; Jeffrey M Venstrom; Geoffrey R Oxnard Journal: Clin Cancer Res Date: 2021-02-08 Impact factor: 13.801
Authors: Stephanie O Dudzinski; Brent D Cameron; Jian Wang; Jeffrey C Rathmell; Todd D Giorgio; Austin N Kirschner Journal: J Immunother Cancer Date: 2019-08-14 Impact factor: 13.751
Authors: Neal Shore; Christian Zurth; Robert Fricke; Hille Gieschen; Kristina Graudenz; Mikko Koskinen; Bart Ploeger; Jonathan Moss; Olaf Prien; Gustavo Borghesi; Oana Petrenciuc; Teuvo L Tammela; Iris Kuss; Frank Verholen; Matthew R Smith; Karim Fizazi Journal: Target Oncol Date: 2019-10 Impact factor: 4.493
Authors: Alberto Lapini; Orazio Caffo; Giovanni Pappagallo; Roberto Iacovelli; Rolando Maria D'Angelillo; Vittorio Vavassori; Roberta Ceccarelli; Sergio Bracarda; Barbara Alicja Jereczek-Fossa; Luigi Da Pozzo; Giario Natale Conti Journal: Cancers (Basel) Date: 2019-12-01 Impact factor: 6.639
Authors: Erik M Velez; Bhushan Desai; Lingyun Ji; David I Quinn; Patrick M Colletti; Hossein Jadvar Journal: Theranostics Date: 2020-02-10 Impact factor: 11.556
Authors: Wout Devlies; Markus Eckstein; Alessia Cimadamore; Gaëtan Devos; Lisa Moris; Thomas Van den Broeck; Rodolfo Montironi; Steven Joniau; Frank Claessens; Thomas Gevaert Journal: Cells Date: 2020-11-17 Impact factor: 6.600