Metastasis-free survival as a predictor of overall survival in non-metastatic castration-resistant prostate cancer.

2019 ◽  
Vol 37 (7_suppl) ◽  
pp. 201-201 ◽  
Author(s):  
Richard Gagnon ◽  
Nimira S. Alimohamed ◽  
Eugene Batuyong ◽  
Alyssa Chow ◽  
Richard M. Lee-Ying

201 Background: Recent trials have shown that apalutamide and enzalutamide can improve metastasis free survival (MFS) in advanced non-metastatic (M0) castrate-resistant prostate cancer (CRPC). MFS is a novel clinical endpoint, demonstrated to be a strong predictor of overall survival (OS) for localized prostate cancer, yet it is unknown if this is also true for M0 CRPC. Our aim was to determine how strongly MFS in M0 CRPC correlates with OS in a real world population. Secondary analyses evaluated whether a rapid PSA-doubling time (PSADT), of ≤10 months, impacts outcomes. Methods: We performed an analysis of patients diagnosed with advanced prostate cancer, followed at the Tom Baker Cancer Centre, in Calgary, Alberta from 2001-2017. Patients were excluded if they did not develop M0 CRPC. MFS and OS were measured using the Kaplan-Meier method and the log-rank test was used to compare outcomes based on PSADT. Correlation between OS and MFS was determined using Pearson Correlation and Kendall’s Tau-B. Results: A total of 1310 patients were identified with advanced prostate cancer, of which 87 developed M0 CRPC. The median age of diagnosis of M0 CRPC was 72 years, with a median Gleason score of 7.0, initial PSA of 10.4, and PSADT of 5.1 months. Only 6 patients were treated with second-generation anti-androgens or chemotherapy. Median MFS and OS after M0 CRPC diagnosis were 44.1 and 83.7 months, respectively. Pearson Correlation between MFS and OS was strong with a coefficient of 0.850 (p < 0.001); with non-parametric Kendall’s Tau, correlation was also strong with a coefficient of 0.632 (p < 0.001). PSADT ≤10 months was identified in 70 patients, and associated with a significantly shorter MFS, compared to a PSADT > 10 months (40.2 vs. 90.4 months; p = 0.001), as well as shorter OS (76.2 vs. 104.3 months; p = 0.008). Conclusions: MFS for M0 CRPC is strongly correlated with OS in a real world population. PSADT of ≤10 months seems to be a useful prognostic tool in estimating MFS and OS in patients with M0 CRPC. MFS was better than expected even in patients with a PSADT of ≤10 months, which may due to our adherence to the biochemical definition of castration-resistant disease, as well as lack of standard imaging intervals in the real world.

2020 ◽  
Vol 12 ◽  
pp. 175883592096872
Author(s):  
Giuseppe Procopio ◽  
Vincenzo Emanuele Chiuri ◽  
Monica Giordano ◽  
Giovanna Mantini ◽  
Roberto Maisano ◽  
...  

Background: Real-world data on chemotherapy-naïve patients with metastatic castration-resistant prostate cancer (mCRPC) treated with abiraterone plus prednisone are limited, largely deriving from small retrospective studies. Methods: ABitude is an Italian, observational, prospective, multicenter study of mCRPC patients receiving abiraterone plus prednisone in clinical practice. Chemotherapy-naïve mCRPC patients were consecutively enrolled at abiraterone start (February 2016 to June 2017) and are being followed for 3 years, with evaluation approximately every 6 months. Several clinical and patients reported outcomes were examined. Results: In this second interim analysis, among 481 enrolled patients, 453 were evaluable for analyses. At baseline, the median age was 77 years and ~69% of patients had comorbidities (mainly cardiovascular diseases). Metastases were located mainly at bones and lymph nodes; 8.4% of patients had visceral metastases. During a median follow-up of 18 months, 1- and 2-year probability of radiographic progression-free survival were 73.9% and 56.2%, respectively; the corresponding rates for overall survival were 87.3% and 70.4%. In multivariable analyses, the number of bone metastases significantly affected radiographic progression-free survival and overall survival. During abiraterone plus prednisone treatment, 65% of patients had a ⩾50% prostate-specific antigen decline, and quality of life remained appreciably high. Among symptomatic patients according to the Brief Pain Inventory) (32%), scores significantly declined after 6 months of treatment. Overall, eight patients (1.7%) had serious adverse reactions to abiraterone. Conclusions: Abiraterone plus prednisone is effective and safe for chemotherapy-naïve mCRPC patients in clinical practice.


2020 ◽  
Vol 12 ◽  
pp. 175883592097813
Author(s):  
Pernelle Lavaud ◽  
Clément Dumont ◽  
Constance Thibault ◽  
Laurence Albiges ◽  
Giulia Baciarello ◽  
...  

Until recently, continuing androgen deprivation therapy (ADT) and closely monitoring patients until evolution towards metastatic castration-resistant prostate cancer (CRPC) were recommended in men with non-metastatic CRPC (nmCRPC). Because delaying the development of metastases and symptoms in these patients is a major issue, several trials have investigated next-generation androgen receptor (AR) axis inhibitors such as apalutamide, darolutamide, and enzalutamide in this setting. This review summarizes the recent advances in the management of nmCRPC, highlighting the favourable impact of next-generation AR inhibitors on metastases-free survival, overall survival and other clinically meaningful endpoints.


Author(s):  
Mikifumi Koura ◽  
Masaki Shiota ◽  
Shohei Ueda ◽  
Takashi Matsumoto ◽  
Satoshi Kobayashi ◽  
...  

Abstract Objective This study aimed to reveal the prognostic values of prior local therapy in first-line therapy using androgen receptor-axis targeting agents (abiraterone or enzalutamide) or docetaxel for castration-resistant prostate cancer (CRPC). Methods The study included 303 patients treated with first-line therapy for non-metastatic and metastatic CRPC. The association between prior local therapy and therapeutic outcome including progression-free survival and overall survival was investigated by univariate and multivariate analyses as well as propensity score-matched analysis. Results In univariate analysis, local prior therapy was associated with a lower risk of all-cause mortality (hazard ratio, 0.56, 95% confidence interval, 0.40–0.79; P = 0.0009). Overall survival, but not progression-free survival, was better among patients with prior local therapy compared with patients without prior local therapy even after multivariate analysis and propensity score-matched analysis. Conclusions This study robustly indicated that prior local treatment was prognostic for overall survival among patients with CRPC. This finding is useful to predict patient prognosis in CRPC.


2020 ◽  
Vol 77 (6) ◽  
pp. 763-766 ◽  
Author(s):  
David Lorente ◽  
Elena Castro ◽  
Rebeca Lozano ◽  
Javier Puente ◽  
Nuria Romero-Laorden ◽  
...  

2018 ◽  
pp. 1-12 ◽  
Author(s):  
Hideyuki Akaza ◽  
Giuseppe Procopio ◽  
Choosak Pripatnanont ◽  
Gaetano Facchini ◽  
Sergio Fava ◽  
...  

Purpose There is a major clinical need to devise an optimal treatment sequence for the multiple therapy options available for patients with metastatic castration-resistant prostate cancer (mCRPC). In the absence of prospective clinical trials, sequencing information can be derived from large, real-world registry studies. Patients and Methods PROXIMA (Treatment Patterns in Patients With Metastatic Castration-Resistant Prostate Cancer Previously Treated With Docetaxel-Based Chemotherapy) is a large, global, prospective registry study evaluating real-world treatment patterns of patients with mCRPC who experience disease progression during or after docetaxel therapy. Patients were enrolled worldwide between 2011 and 2014. Treatments were determined by the treating physicians and recorded in categories of chemotherapy, hormonal therapy, targeted therapy, immunotherapy, and palliative therapy. Treatment sequencing patterns, response to treatment, and types of progression were recorded and analyzed. Progression-free survival and overall survival with different treatment modalities were analyzed using Kaplan–Meier method. Results Treatment patterns were evaluated in 903 patients. Therapy selection was influenced by region. Hormonal therapy (57.5%) and taxane chemotherapy (26.4%) were the most frequently administered first subsequent treatments after docetaxel. Tumor responses to first subsequent treatment were observed in 22.6% of evaluable patients. Overall survival and progression-free survival did not differ significantly across different treatment modalities. Conclusion Identifying an optimal treatment sequence is vital for improving the care of patients with mCRPC. The PROXIMA registry provided a representative sample of global data on real-world treatment patterns for patients with mCRPC previously treated with docetaxel. These data can be used to devise optimal therapy sequences and inform treatment decisions.


2019 ◽  
Vol 13 ◽  
pp. 117955491983392 ◽  
Author(s):  
Joelle El-Amm ◽  
Jeanny B Aragon-Ching

Non-metastatic castration-resistant prostate cancer (nmCRPC) is a heterogeneous disease with variable potential in developing into overt metastases. It is an area of increased unmet need in advanced prostate cancer and for which there had been no great treatments until recent US Food and Drug Administration (FDA) approval of 2 novel anti-androgens apalutamide and enzalutamide, which were both approved given benefit in metastasis-free survival. Early data on the use of darolutamide, another novel anti-androgen, are also explored. This review discusses the pivotal trials that led to the approval of apalutamide and enzalutamide in the nmCRPC setting and discusses the key promises and challenges with the use of these agents.


2021 ◽  
Author(s):  
Toshikazu Tanaka ◽  
Shingo Hatakeyama ◽  
Daisuke Noro ◽  
Hirotake Kodama ◽  
Sakae Konishi ◽  
...  

Abstract We investigated the effect of upfront intensive therapy on primary resistance in patients with metastatic castration-sensitive prostate cancer (mCSPC) in real-world practice. We retrospectively evaluated the medical records of 348 patients with newly diagnosed mCSPC who had a high tumor-burden between January 2008 and May 2021. We compared the oncological outcomes between patients who received conventional androgen deprivation therapy ± bicalutamide (ADT group) and those treated with upfront intensive therapies (upfront group). The primary purpose was comparing the rate of primary resistance between the ADT and upfront groups. The primary resistance was defined as a castration-resistant prostate cancer (CRPC) progression < 6 or < 12 months. The secondary purposes were comparing the CRPC-free survival and overall survival (OS) between the ADT and upfront groups, and assessing safety in the upfront group. We identified 206 and 142 patients for the ADT and upfront groups, respectively. We found the rate of CRPC progression < 6 and < 12 months was significantly lower in the upfront group (9.2% and 18%, respectively) than that in the ADT group (21% and 51%, respectively). The upfront therapy was significantly associated with favorable CRPC-free survival and OS than that in the ADT group in propensity-score adjusted models. A higher rate of any grade adverse events was observed in the upfront docetaxel (94%) than that of the upfront abiraterone (34%) or apalutamide/enzalutamide (39%). In conclusion, the upfront intensive therapy significantly improved the rate of primary resistance and oncological outcomes in patients with mCSPC in real-world practice.


2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 97-97
Author(s):  
Cedric Pobel ◽  
Edouard Auclin ◽  
Diego Teyssonneau ◽  
Brigitte Laguerre ◽  
Mathilde Cancel ◽  
...  

97 Background: Cabazitaxel rechallenge could be a more efficient therapy with an acceptable toxicity than docetaxel in the treatment of patients with a metastatic castration resistant prostate cancer (mCRPC). The aim of this study was to assess the feasibility and efficacy of cabazitaxel multiple rechallenge. Methods: This is a multicenter, retrospective cohort study including patients from 9 centers in France who received 3 lines or more of cabazitaxel from February 2012 to July 2020. Cabazitaxel schedule differed between patients: 25 mg/m2 q3w, 20 mg/m2 q3w, 16 mg/m2 q2w or 10 mg/m2 weekly. Efficacy was assessed by overall survival (OS) and progression-free survival (PFS) from each cabazitaxel line start. Only toxicities grade ≥ 3 were reported. Results: Twenty-two patients were included. The median follow-up from mCRPC was 94.7 months, median age at initial diagnosis was 59.5 years old, median ISUP score at diagnosis was 4 and median PSA at diagnosis was 55 ng/ml. Median number of cabazitaxel cycles was 7 at first-line, 6 at first rechallenge, and 5 for subsequent rechallenges. Median OS from mCRPC diagnosis was 105 months. Median PFS from cabazitaxel line start was 11.8 months at first use, 9.6 for first rechallenge and 5.6 in second rechallenge (table). Only one case of febrile neutropenia and 6 events of grade ≥ 3 toxicity were reported. Conclusions: Cabazitaxel multiple rechallenge could efficiently extend OS with manageable toxicities for patients. Even if anti-PARP therapy and immunotherapy are promising treatments, cabazitaxel rechallenge could be also a relevant therapeutic option for long responder patients. Specific biomarkers should be explored to predict the efficacy of cabazitaxel rechallenge. [Table: see text]


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