Efficacy, quality of life, and safety of cabazitaxel in Canadian metastatic castration-resistant prostate cancer patients treated or not with prior abiraterone

Abstract

Introduction: In the TROPIC study, cabazitaxel improved overall survival in abiraterone-naïve metastatic castration-resistant prostate cancer (mCRPC) patients post-docetaxel. To evaluate cabazitaxel in routine clinical practice, an international, single-arm trial was conducted. Efficacy, safety, and quality of life (QoL) data were collected from Canadian patients enrolled. Overall survival and progression-free survival were not collected as part of this study. Importantly, prior abiraterone use was obtained and its impact on clinical parameters was examined. Methods: Sixty-one patients from nine Canadian centres were enrolled, with prior abiraterone use known for 60 patients. Prostatespecific antigen (PSA) response rate, safety, and impact on QoL life were analyzed as a function of prior abiraterone use. Results: Overall, 92% of patients were ECOG 0/1, 88% had bone metastases, and 25% visceral metastases. Patients treated without prior abiraterone (NoPriorAbi) (n=35, 58%) and with prior abiraterone (PriorAbi) (n=25, 42%) had similar baseline characteristics, except for age and prior cumulative docetaxel dose. Median number of cabazitaxel cycles received was similar between groups (NoPriorAbi=6, PriorAbi=7), as was PSA response rate (NoPriorAbi=36.4%, PriorAbi=45.0%, p=0.54). Almost one-third (31%) of patients received prophylactic granulocyte colony-stimulating factors. Most frequent Grade 3/4 toxicities were neutropenia (14.8%); anemia, febrile neutropenia, fatigue (each at 9.8%); and diarrhea (8.2%). No treatment-related adverse event leading to death was observed. QoL and pain were improved with no difference seen between groups. Treatment discontinuation was mainly due to disease progression (45.9%) and adverse events (32.8%). Conclusions:In routine clinical practice, cabazitaxel's risk-benefit ratio in mCRPC patients previously treated with docetaxel seems to be maintained independent of prior abiraterone use.

Prognostic and predictive clinical factors in patients with metastatic castration-resistant prostate cancer treated with cabazitaxel

“…It has been previously shown that prior abiraterone does not impact the response rate for patients treated with cabazitaxel. [23][24][25][26][27] The same study also found that prior abiraterone or the duration or response to abiraterone did not influence treatment response to cabazitaxel. This study was done prior to approvals of enzalutamide and radium-223 so these factors could not be addressed.…”

“…Primary prophylaxis with granulocyte-colony stimulating factor (G-CSF) was permitted. 26 Patients from four centres in Ontario and one in Quebec were included. Data from the C-EAP was supplemented by a retrospective chart review including patient and disease factors, treatment factors and baseline laboratory values.…”

“…Multiple studies have also assessed the impact of prior abiraterone or enzalutamide on activity of cabazitaxel and all have shown that cabazitaxel continues to be active in this setting. [23][24][25][26][27] Ultimately, there is insufficient evidence to know which clinical factors will predict for a response to cabazitaxel. Given the dearth of information regarding prognostic and predictive factors for patients treated with cabazitaxel in routine clinical practice, we analyzed data from patients treated with cabazitaxel as part of the Canadian Early Access Program (C-EAP) to better understand routine clinical factors that may influence prognosis and identify which factors may predict for treatment response.…”

Oncologic Response and Hospitalization Rate of Patients Receiving Cabazitaxel in the Fourth-Line and Beyond in Castration-Resistant Prostate Cancer: Analysis of a Retrospective Cohort and a Structured Literature Review

“…Heidenreich et al [23] demonstrated manageable toxicity profiles for CAB use in routine clinical practice post-DOC. Saad et al [19] reported a frequency of grade 3 or higher adverse events in 80% of CAB-treated patients with prior AA and DOC. While the Terminology Criteria for Adverse Events defines the gold standard for adverse event reporting in clinical trials, the patient-centeredness of this instrument is controversial [24].…”

Assessing the utility of cabazitaxel in mCRPC

“…1 These results were generated as part of an international, expanded-access study, in which 61 Canadian men were enrolled and for whom prior abiraterone exposure was known for 60 subjects.…”