Impact of new systemic therapies on overall survival (OS) of patients (pts) with metastatic castration resistant prostate cancer (mCRPC) in a hospital-based registry.

2018 ◽  
Vol 36 (6_suppl) ◽  
pp. 203-203
Author(s):  
Edoardo Francini ◽  
Kathryn P. Gray ◽  
Grace Shaw ◽  
Carolyn Evan ◽  
Anis Hamid ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Proportional Hazards Model ◽  
Multivariable Analysis ◽  
Cox Proportional Hazards Model ◽  
Castration Resistant Prostate Cancer ◽  
New Therapies ◽  
Risk Of Death ◽  
Radium 223 ◽  
Ecog Ps

203 Background: From 2004 to 2009, mCRPC treatment options were limited to docetaxel (D), mitoxantrone, first generation anti-androgens (AA), estrogens, steroids, and ketoconazole, with only D showing OS benefit. Since 2010, five new therapies prolonged OS and were approved for mCRPC: sipuleucel-T, cabazitaxel, abiraterone acetate, enzalutamide, and radium 223. We sought to assess the aggregate impact of new therapies on OS. Methods: We used the DFCI CRIS database to identify cohorts of pts who developed mCRPC between 2004-2007 (cohort A) and 2010-2013 (cohort B). Therapies for mCRPC in each cohort were annotated. Given the median follow-up (FU) was 10.6 years (yrs) in cohort A and 4.6 yrs in cohort B, we evaluated OS, defined as time from mCRPC per PCWG3 criteria to death from all causes or last follow-up visit within 5 yrs (truncated OS). Kaplan-Meier method estimated the time to events distribution with median (95% CI). Cox proportional hazards model evaluated effects of treatment groups on disease outcomes with estimates of hazard ratio (95% CI). Results: Of the 583 pts identified, 317 (54%) were in cohort A and 266 (46%) in cohort B. Pts in cohort B had a significantly longer median OS (p<0.001), a 5-yr OS of 26% vs. 10%, and a 31% reduced risk of death compared to cohort A (HR=0.69; 95% CI, 0.57-0.83) (see Table). On multivariable analysis, adjusting for prior local Rx, ECOG PS, and the number of agents received, longer OS is confirmed associated with cohort B vs. A and also with ECOG PS status 0 vs. 1, number of agents received 5-12 vs. ≤3. Conclusions: Using the DFCI prostate cancer database, therapies approved for mCRPC since 2010 showed a modest impact on OS, with a median improvement of 6 months. There was a more substantial effect on long term survivors with 2.6 fold increase of 5-yr OS. [Table: see text]

Impact of circulating tumor cell (CTC) nucleus size on outcomes with abiraterone acetate (AA) therapy in men with metastatic castration-resistant prostate cancer (mCRPC).

2017 ◽  
Vol 35 (6_suppl) ◽  
pp. 253-253
Author(s):  
David Michael Gill ◽  
Neeraj Agarwal ◽  
Andrew W. Hahn ◽  
Eric Johnson ◽  
Austin Poole ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Proportional Hazards Model ◽  
Multivariable Analysis ◽  
Cox Proportional Hazards ◽  
Significant Trend ◽  
Cox Proportional Hazards Model ◽  
Nuclear Size ◽  
Nucleus Size ◽  
Castration Resistant Prostate Cancer ◽  
The Impact

253 Background: CTC enumeration but not CTC morphology has been reported to predict outcomes to treatment in men with mCRPC. Recently Chen JF et. al (Cancer, 2015) showed an association with nuclear size and incidence of visceral disease in metastatic prostate cancer. In this study, we investigate the impact of CTC nucleus size on outcomes in men treated with AA for mCRPC. Methods: In a cohort of men with mCRPC treated with first-line AA, who had CTCs identified by CellSearch (CS) analysis prior to initiating treatment, we retrospectively quantified the nuclear size of CTCs by ImageJ/Fiji 1.46 software and correlated with progression free survival (PFS) on AA. We analyzed with univariate in addition to pre-specified multivariable analysis adjusted for Gleason score and baseline log PSA to assess independent predictive value of CTC nuclear size on PFS. Median PFS was calculated by Kaplan-Meier analysis and p-values were determined from Cox proportional hazards model. Results: 22 men treated with AA for mCRPC were included. Median nucleus size was 23.8 µm. Patients were divided in to 2 cohorts: small nuclear cohort (CTC nucleus size < 23.8 µm) vs large nuclear cohort (CTC nucleus size ≥23.8 µm). There was a non-significant trend towards worsened PFS (5.8 versus 6.8 months) in the larger nuclear size arm (Table). Conclusions: In this cohort of men with CRPC treated with AA, there is a non-significant trend towards decreased PFS associated with larger CTC nucleus size. Data are hypothesis generating and require further interrogation in a larger cohort. [Table: see text]

Relationship between quality of life and overall survival in metastatic castration-resistant prostate cancer (mCRPC) patients in ALSYMPCA.

2017 ◽  
Vol 35 (6_suppl) ◽  
pp. 177-177
Author(s):  
Sten Nilsson ◽  
A. Oliver Sartor ◽  
Nicholas J. Vogelzang ◽  
Robert E. Coleman ◽  
Joe M. O'Sullivan ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Overall Survival ◽  
Proportional Hazards Model ◽  
Well Being ◽  
Cox Proportional Hazards Model ◽  
Castration Resistant Prostate Cancer ◽  
Risk Of Death ◽  
Radium 223 ◽  
Baseline Hrqol

177 Background: Radium-223 improved overall survival (OS) with meaningful improvements vs placebo in health-related quality of life (HRQoL) in phase 3 ALSYMPCA (Parker NEJM 2013; Nilsson Ann Oncol 2016). We examined the relationship of OS to HRQoL scores at baseline or change from baseline. Methods: HRQoL in ALSYMPCA was assessed by FACT-P questionnaire at baseline, during treatment (wk 16, 24), and follow-up. Cox proportional hazards model for OS was fitted using HRQoL baseline scores and included previously identified covariates: treatment (radium-223 vs placebo); log10 baseline LDH, ALP, and PSA; age; baseline ECOG-PS; and albumin. A time-dependent model also included change from baseline HRQoL scores. Results: Analysis includedbetween 810-836 patients with baseline HRQoL scores for various FACT-P metrics. Significant associations were seen between OS and FACT-P total score at baseline or change from baseline. Every 10-point increase in FACT-P total score (ie, improvement) was associated with 7% decreased risk of death (Table). Results for FACT-P subscales were similar, except social well-being. Conclusions: This analysis of ALSYMPCA data shows that baseline HRQoL and changes in HRQoL are prognostic of OS in mCRPC. Clinical trial information: NCT00699751. [Table: see text]

Correlation between baseline variables and survival in the radium-223 dichloride (Ra-223) phase III ALSYMPCA trial with attention to total ALP changes.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 5080-5080 ◽  
Author(s):  
A. Oliver Sartor ◽  
Roy Amariglio ◽  
Scott Wilhelm ◽  
Jose E. Garcia-Vargas ◽  
C. Gillies O'Bryan-Tear ◽  
...  
Keyword(s):  
Proportional Hazards Model ◽  
Cox Regression ◽  
Performance Status ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Phase Iii ◽  
Castration Resistant Prostate Cancer ◽  
Risk Of Death ◽  
Radium 223 ◽  
Increased Risk

5080 Background: In patients (pts) with castration-resistant prostate cancer and bone metastases (mCRPC), total ALP (tALP) has been shown to be a prognostic marker for overall survival (OS) (Cook 2006). Here the prognostic value of tALP and other baseline clinical variables in Ra-223 pts is presented, along with the initial results of an exploratory analysis of changes in tALP seen with Ra-223. Methods: Study population included 921 pts (intent-to-treat population) from the ALSYMPCA trial. The Cox proportional hazards model was used to evaluate the prognostic potential of tALP and other baseline variables (albumin, Hb, LDH, ECOG performance status, PSA, and age). Log transformation was done for baseline variables (tALP, PSA, and LDH) with heavily skewed distributions. Baseline variables were assessed for interaction with treatment. To determine changes in tALP from baseline at 12 wk, 708 pts who had tALP measurements at both baseline and 12 wk were included. Results: The baseline variables in the Table were significantly associated with OS. Hb was not a significant factor when adjusting for all other covariates and was therefore removed from the final Cox regression model. No significant treatment-by-covariate interactions were detected. After controlling for other variables, higher baseline tALP was significantly associated with an increased risk of death (p < 0.0001). At 12 wk, a decline in tALP relative to baseline was seen in 87% (433/497) of Ra-223 pts, compared to 23% (49/211) of placebo pts. The mean percentage change from baseline in tALP at 12 wk was a 32% decline for Ra-223 pts, in contrast to a 37% increase for placebo pts (p< 0.001). Conclusions: In mCRPC pts, higher baseline levels of tALP were associated with an increased risk of death. With the majority of Ra-223 pts experiencing a decline in tALP at 12 wk, and the marked mean percentage tALP decline in these pts, further analysis to determine a correlation between tALP dynamics and survival is warranted. Clinical trial information: NCT00699751. [Table: see text]

Pain analyses from the phase III randomized ALSYMPCA study with radium-223 dichloride (Ra-223) in castration-resistant prostate cancer (CRPC) patients with bone metastases.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 5038-5038 ◽  
Author(s):  
Sten Nilsson ◽  
A. Oliver Sartor ◽  
Oyvind S. Bruland ◽  
Fang Fang ◽  
Anne-Kirsti Aksnes ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Bone Metastases ◽  
Severe Pain ◽  
Proportional Hazards Model ◽  
Cox Proportional Hazards Model ◽  
Phase Iii ◽  
Injection Pain ◽  
Castration Resistant Prostate Cancer ◽  
Opioid Use ◽  
Radium 223

5038 Background: Bone metastases (mets), present in > 90% of patients (pts) with CRPC, may cause severe pain. In a phase 2 dose-response study with a single injection of Ra-223, pain response was seen in up to 71% of CRPC pts with painful bone mets (Nilsson 2012). In the phase 3 ALSYMPCA study, which included 921 CRPC pts with bone mets randomized 2:1 to receive 6 injections of Ra-223 (50 kBq/kg IV) q4wk or matching placebo (Ra-223, n = 614; placebo, n = 307), Ra-223 significantly improved overall survival vs placebo (median 14.9 vs 11.3 mo; HR = 0.695) and was well tolerated. Post hoc analyses of pain parameters in ALSYMPCA are presented. Methods: The Cox proportional hazards model was used to analyze time to initial opioid use and time to EBRT. Pts with no opioid use at baseline were included in the pain analyses. All pts were included in the analysis for the prespecified endpoint time to EBRT. Concomitant opioid use was recorded from first study drug injection to 12 weeks after last injection. Pain-related QOL was analyzed based on the sum of 4 questions within FACT-P prostate cancer subscale (PCS) (Cella 2009) using ANCOVA. Results: Baseline pain characteristics were similar between the treatment groups (approximately 55% of pts had moderate to severe pain and opioid use based on WHO ladder for cancer pain). Time to EBRT was significantly longer with Ra-223 vs placebo (HR = 0.670; 95% CI, 0.525-0.854). Despite a longer observation time, fewer Ra-223 pts (50%) than placebo pts (62%) reported bone pain as an AE. At baseline, 269 Ra-223 pts and 139 placebo pts did not use opioids. Median time to initial opioid use was significantly longer in the Ra-223 group, with a risk reduction of 38%, compared to placebo (HR = 0.621; 95% CI, 0.456-0.846). Fewer Ra-223 pts (36%) than placebo pts (50%) required opioids for pain relief. The QOL pain score indicated reduced pain for Ra-223 pts relative to placebo pts at week 16 (P = 0.001). Ra-223 pts had significant pain reduction relative to baseline at weeks 16 (P < 0.001 ) and 24 (P = 0.001). Conclusions: These results provide consistent evidence that, in addition to prolonging survival, Ra-223 reduces pain and opioid use in CRPC pts with bone mets. Clinical trial information: NCT00699751.

Decreased fracture rate by mandating bone protecting agents in the EORTC 1333/PEACEIII trial combining Ra223 with enzalutamide versus enzalutamide alone: An updated safety analysis.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 5002-5002
Author(s):  
Silke Gillessen ◽  
Ananya Choudhury ◽  
Alejo Rodriguez-Vida ◽  
Franco Nole ◽  
Enrique Gallardo Diaz ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Safety Analysis ◽  
Phase Iii ◽  
Fracture Rate ◽  
Castration Resistant Prostate Cancer ◽  
Continuous Administration ◽  
Castration Resistant ◽  
Radium 223 ◽  
Safety Population

5002 Background: The randomized phase III EORTC-1333-GUCG (NCT02194842) trial compares enzalutamide vs. a combination of Radium 223 and enzalutamide in asymptomatic or mildly symptomatic metastatic castration resistant prostate cancer (mCRPC) patients. The premature unblinding of ERA223 (NCT02043678) in Nov 2017 due to a significant increase in the rate of fractures in the combination of abiraterone and Ra223 arm led to the implementation of the mandatory use of bone protecting agents (BPA) in the EORTC-1333-GUCG trial. Skeletal fractures, pathological or not, are a frequent and underestimated adverse event of systemic treatment of advanced prostate cancer. Whether this mandated use of BPA (zoledronic acid or denosumab) would mitigate the risk of fractures in this patient population was unclear. An early safety analysis (Tombal, ASCO, 2019) suggested that the risk of fractures was well controlled in both arms when patients receive BPA. We present here an updated analysis of fracture incidence with longer follow-up. Methods: As of 28/01/2021, a total of 253 patients (134 after making BPA mandatory) were randomized between enzalutamide/Ra223 and enzalutamide. The fracture rate was estimated with the cumulative incidence method in the safety population of 237 (122 after making BPA mandatory) treated patients. Death in absence of fracture was analyzed as competing risk and censoring was applied at last follow-up. Results: Overall, 69.5% of enzalutamide/Ra223 patients (95.2% after making BPA mandatory) and 73.1% of enzalutamide patients (95% after making BPA mandatory) received BPA on treatment: 13.6% in the enzalutamide/Ra223 arm and 21.8% in the enzalutamide arm did not use BPA at registration, but started during protocol treatment and 55.9% and 51.3% respectively, received BPA since entry. At 36.7 months median follow-up in patients without BPA and 23.1 months median follow-up in patients receiving BPA, a total of 39 patients reported a fracture. Among them, 30 patients (20 in enzalutamide/Ra223 arm) did not receive BPA and 9 (4 in the enzalutamide/Ra223 arm) received BPA (see table). Conclusions: The updated safety analysis confirms the early fracture rate results. In the absence of BPA, the risk of fracture is increased when RA223 is added to enzalutamide. Strikingly, in both arms, the risk remains almost abolished by a preventive continuous administration of BPA, thus stressing the importance of complying to international recommendations in terms of giving BPA to mCRPC patients. This study is sponsored by EORTC and supported by Bayer and Astellas. Clinical trial information: NCT02194842. [Table: see text]

scholarly journals Re‐treatment with radium‐223: 2‐year follow‐up from an international, open‐label, phase 1/2 study in patients with castration‐resistant prostate cancer and bone metastases

The Prostate ◽  
2019 ◽  
Vol 79 (14) ◽  
pp. 1683-1691 ◽  
Author(s):  
Oliver Sartor ◽  
Daniel Heinrich ◽  
Neil Mariados ◽  
Maria José Méndez Vidal ◽  
Daniel Keizman ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Bone Metastases ◽  
Phase 1 ◽  
Castration Resistant Prostate Cancer ◽  
Open Label ◽  
Castration Resistant ◽  
Radium 223 ◽  
Open Label Phase

Racial disparities in radium-223 treatment in a large real-world population.

2019 ◽  
Vol 37 (7_suppl) ◽  
pp. 268-268
Author(s):  
Hanson Hanqing Zhao ◽  
Lauren Howard ◽  
Amanda de Hoedt ◽  
Martha K Terris ◽  
Christopher L. Amling ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Black Men ◽  
Real World ◽  
Multivariable Analysis ◽  
Treatment Patterns ◽  
World Population ◽  
Castration Resistant Prostate Cancer ◽  
Cox Models ◽  
Radium 223 ◽  
To Receive

268 Background: Black men with prostate cancer are more likely to have unfavorable tumor characteristics and are at greater risk of prostate cancer mortality. Radium-223 is a FDA approved treatment for metastatic castration-resistant prostate cancer (mCRPC) that showed a survival benefit in the ALSYMPCA trial, where 94% of the participants were Caucasian. We aim to examine treatment patterns and outcomes of radium-223 in a large, heterogeneous population in the real world. Methods: We reviewed charts of all men with diagnosed with mCRPC in the entire Veterans Affairs (VA) system alive as of January 1st, 2013 who received radium-223. We compared common treatment patterns and characteristics between black and nonblack men. We analyzed predictors of time from radium-223 start to overall survival and time to skeletal related event (SRE) with Cox models. Results: 318 patients with bone mCRPC who received radium-223 were identified. 27% (87/318) were black. Black men were younger (67 vs 70 years, p = 0.001) and had higher PSA and alkaline phosphatase (ALP) levels at radium start (p = 0.014 and 0.017, respectively). There were no significant differences in biopsy Gleason, number of bone metastasis, primary localized treatment (yes/no), PSA doubling time, bone pain, or number of radium injections. Black men had lower mortality risk (HR 0.75; 95% CI 0.57 to 0.98; P = 0.038) on multivariable analysis. Comparison of common treatment patterns between black and nonblack men revealed that black men were more likely to receive other therapies prior to radium, including chemotherapy. Conclusions: Using a large, heterogeneous, real world cohort, we describe differences in treatment patterns and outcomes with radium-223 between black and nonblack men with mCRPC. While black men had a lower risk of mortality in this cohort, they had higher PSA and ALP levels when receiving radium-223. They were also more likely to receive other therapies prior to radium-223, indicating a possible delay in radium use in black men.

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