Patient (pt) characteristics and treatment patterns in the radium (Ra)-223 REASSURE observational study.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 5042-5042 ◽  
Author(s):  
Celestia S. Higano ◽  
Shawn H. Zimberg ◽  
Sabina Dizdarevic ◽  
Lauren Christine Harshman ◽  
John Logue ◽  
...  
Keyword(s):  
Clinical Practice ◽  
Observational Study ◽  
Interim Analysis ◽  
Routine Clinical Practice ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Observation Methods ◽  
Short And Long Term ◽  
Grade 3

5042 Background: Ra-223, a targeted alpha therapy, prolonged survival with good safety in metastatic castration-resistant prostate cancer (mCRPC) in the phase 3 ALSYMPCA trial. REASSURE will evaluate Ra-223 short- and long-term safety in routine clinical practice settings. This is the first planned interim analysis (median 7 mo observation). Methods: This global, prospective, single-arm, observational study enrolled pts with mCRPC with bone metastases (mets) for whom Ra-223 therapy was planned. Follow-up will continue up to 7 years after last Ra-223 dose. Results: 1106 pts (437 N. America, 665 Europe, 4 not recorded) enrolled from 2 Sep 2014 to 22 Sep 2016. Baseline data are available from 583 pts receiving 1st- (1L), 2nd- (2L), or ≥3rd-line (≥3L) Ra-223 for mCRPC(Table). The majority of pts (n=369, 63%) completed 5–6 doses (1L, 70%; 2L, 64%; ≥3L, 49%); median 6 doses (1L,6; 2L, 6; ≥3L, 4). Treatment-emergent drug-related AEs occurred in 215 pts (37%). Post-treatment grade 3/4 thrombocytopenia occurred in 14 pts (2.4%) and anemia in 45 (7.7%). Conclusions: In routine clinical practice, Ra-223 was associated with no short-term safety concerns and appeared to be used in pts with less advanced mCRPC than in ALSYMPCA. The majority of pts on 1L/2L Ra-223 therapy received 5–6 doses. Ra-223 was often used with abiraterone or enzalutamide, but not chemotherapy. The next interim analysis in 2019 will report long-term safety and outcomes on all pts. Clinical trial information: NCT02141438. [Table: see text]

Novel agents’ sequencing following first-line docetaxel in mCRPC patients: CAPRO study.

2016 ◽  
Vol 34 (2_suppl) ◽  
pp. 229-229
Author(s):  
Javier Puente ◽  
Aranzazu Gonzalez del Alba ◽  
Nuria Sala ◽  
María José Méndez-Vidal ◽  
Alvaro Pinto ◽  
...  
Keyword(s):  
Clinical Practice ◽  
Descriptive Study ◽  
Routine Clinical Practice ◽  
Novel Agents ◽  
Castration Resistant Prostate Cancer ◽  
Median Dose ◽  
First Line ◽  
Castration Resistant ◽  
Observational Descriptive Study ◽  
Treatment Table

229 Background: Novel agents, such as abiraterone (A), cabazitaxel (CZ), and enzalutamide are currently available for the treatment of docetaxel (D)-treated metastatic castration resistant prostate cancer (mCRPC). The sequencing approach following D progression is still unknown. We now explore which factors are driving sequencing decisions in routine clinical practice in Spain. Methods: A prospective multicenter national observational descriptive study collecting data of 2nd line (L) treatments in mCRPC patients to analyze responses and progression to 1stL D. Results: 149 patients have been recruited from July 2013 to January 2015. Median age was 72 (48-89). Median D cycles was 6 (1-24), and median dose: 75 mg/m2 (30-75). 24 patients (16%) required dose reduction. The reasons for D ending were treatment completion (40%, n = 60), toxicity (15.3%, n = 23), progression (radiological, biochemical, clinical; 42%, n = 63), or others (2.7%, n = 4). 67% (n = 100) of the patients received A, 25% (n = 44) CZ, and 8% (n = 5) other treatments as 2ndL. From those who completed or progressed to D (n = 123), 2ndL initiation was mainly determined by two progression criteria (2C; biological and radiological), followed by one progression criteria (1C). This was independent of the 2ndL treatment chosen, and it was observed in similar ratios in both A (2C: 50%, n = 39; 1C: 37.2%, n = 29) and CZ (2C: 62.5%, n = 25; 1C: 27.5%, n = 11). Nevertheless, A was predominantly given when patients progressed after D ending, whereas CZ was mostly given when progressing during D (Table 1). Conclusions: A is the 2ndL treatment of choice in routine clinical practice in Spain, independent of the type and time of progression. CZ is preferentially used in patients progressing during D treatment. [Table: see text]

Clinical outcomes and patient (pt) profiles in REASSURE: An observational study of radium-223 (Ra-223) in metastatic castration-resistant prostate cancer (mCRPC).

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 32-32
Author(s):  
Celestia S. Higano ◽  
Fred Saad ◽  
A. Oliver Sartor ◽  
Kurt Miller ◽  
Peter Conti ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Clinical Practice ◽  
Observational Study ◽  
Clinical Outcomes ◽  
Bone Fractures ◽  
Bone Marrow Suppression ◽  
Routine Clinical Practice ◽  
Metastatic Sites

32 Background: Ra-223 is a targeted alpha therapy that showed a survival advantage and favorable safety profile in the phase 3 ALSYMPCA trial in pts with mCRPC. REASSURE (NCT02141438) is evaluating the long-term safety of Ra-223 in routine clinical practice in pts with mCRPC over a 7-year follow-up period. Methods: In this global, prospective, single-arm, observational study, the second prespecified interim analysis (data cut-off March 2019) evaluated safety and clinical outcomes of Ra-223 in pts with mCRPC. Primary outcome measures were incidence of second primary malignancies (SPM), bone marrow suppression and short- and long-term safety in pts who had ≥1 Ra-223 dose. Secondary outcomes included overall survival (OS). Results: For 1465 pts in the safety analysis, median follow up was 11.5 months. Median PSA (n=1053), ALP (n=1048), and LDH (n=555) levels at baseline were 59 ng/mL, 135 U/L, and 269 U/L, respectively. 81% of pts had bone metastases only at baseline; 19% of pts had other metastatic sites, mostly in the lymph nodes. 19% of pts had <6 metastatic sites, 47% had 6–20 sites, 20% had >20 lesions but not a superscan, and 6% had a superscan. 45%, 38%, 37%, 9%, and 8% of pts received prior abiraterone, docetaxel, enzalutamide, cabazitaxel, or sipuleucel-T as prior therapies, respectively. Median number of Ra-223 doses received was 6; 67% of pts had ≥5 doses. SPM occurred in 1% of pts. The most common treatment-emergent drug-related adverse event (AE) of any grade was diarrhea (11%). 10% of pts had a bone-associated event, 5% had fractures, and 15% had a hematological AE. Median OS was 15.6 months (95% CI 14.6–16.5). Conclusions: In REASSURE, there was a low incidence of SPM, bone fractures, and bone marrow suppression after Ra-223 treatment, with no new AEs identified. This study confirms that in routine clinical practice, Ra-223 AE rates were low, and pts generally received ≥5 doses. Clinical trial information: NCT02141438. [Table: see text]

Assessment of corticosteroid (CS)-associated adverse events (AEs) with long-term (LT) exposure to low-dose prednisone (P) given with abiraterone acetate (AA) to metastatic castration-resistant prostate cancer (mCRPC) patients (Pts).

2015 ◽  
Vol 33 (7_suppl) ◽  
pp. 169-169 ◽  
Author(s):  
Karim Fizazi ◽  
Kim N. Chi ◽  
Johann Sebastian De Bono ◽  
Leonard G. Gomella ◽  
Kurt Miller ◽  
...  
Keyword(s):  
Low Dose ◽  
Compression Fracture ◽  
Abiraterone Acetate ◽  
High Dose ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Common Grade ◽  
Low Incidence ◽  
Grade 3

169 Background: AA is the prodrug of abiraterone, which inhibits CYP17A1 and testosterone synthesis and prolongs survival of mCRPC pts. A low dose of P is given when AA is administered to mCRPC pts. LT use of moderate-/high-dose CS has an established AE profile. We investigated whether LT use of low-dose P with or without AA led to CS-associated AEs. Methods: 2,267 mCRPC pts in COU-AA-301 and COU-AA-302 received 5 mg bid P, representing 2,006 pt-yrs of P exposure. 1,333 pts received AA + P. We utilized an inclusive Standardized MedDRA Queries–oriented approach to identify 112 preferred terms for known CS-associated AEs from both databases. CS-associated AEs during 3-mo exposure intervals and across all exposure to P were assessed. Results: The overall incidence of CS-associated AEs for any P exposure was 25%, 26%, and 23% for all pts, AA + P, and P alone, respectively. The incidence of grade ≥ 3 CS-associated AEs with any P exposure was 5%, 5%, and 4% for all pts, AA + P, and P alone, respectively. The most common grade ≥ 3 CS-associated AEs occurring in ≥ 0.1% of all pts were hyperglycemia (2%), cataract (0.4%), diabetes mellitus (0.4%), gastrointestinal hemorrhage (0.3%), adrenal insufficiency (0.1%), hip fracture (0.1%), melena (0.1%), and spinal osteoporotic compression fracture (0.1%). The overall incidence of weight increase (grade 1/2 only) was 4%, 4%, and 5% for all pts, AA + P, and P alone, respectively. Most were grade 1 (3.4%).When assessed by duration of exposure (3-mo intervals up to ≥30 mo), grade ≥ 3 CS-associated AEs fluctuated between 1% and 2%, but no discernable trend was observed. The observed change in weight from baseline showed no apparent increase over time. Conclusions: With over 2,000 pt-yrs of exposure, low-dose P given with or without AA is associated with an overall low incidence of CS-associated AEs. The frequencies of CS-associated AEs were low with increased duration of exposure to P. Clinical trial information: NCT00638690 , NCT00887198 .

scholarly journals Effectiveness and Safety Outcomes in Patients with Hemophilia a Receiving Antihemophilic Factor (Recombinant) for at Least 5 Years in a Real-World Setting: 6-Year Interim Analysis of the Ahead International and German Studies

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 1-1
Author(s):  
Dimitrios A. Tsakiris ◽  
Johannes Oldenburg ◽  
Robert Klamroth ◽  
Benoît Guillet ◽  
Kate Khair ◽  
...  
Keyword(s):  
Clinical Practice ◽  
Real World ◽  
Interim Analysis ◽  
Research Funding ◽  
Hemophilia A ◽  
Routine Clinical Practice ◽  
Publicly Traded ◽  
Real World Setting ◽  
Antihemophilic Factor

Introduction: Long-term effectiveness and safety data in patients treated in routine clinical practice settings can be captured from real-world studies. The international (INT) and German (GER) Antihemophilic factor (recombinant; rAHF) Hemophilia A (HA) outcome Database (AHEAD) studies assess long-term effectiveness and safety outcomes in patients with moderate HA (factor VIII level 1-5%) or severe HA (factor VIII &lt;1%) receiving rAHF (ADVATE®; Baxalta US Inc., a Takeda company, Lexington, MA, USA) in routine clinical practice. Methods: These are non-interventional, prospective, long-term, multicenter studies (INT: NCT02078427; GER: DRKS 00000556). Key outcomes include Gilbert scores (primary endpoint; pain scored 0-3; bleeding scored 0-3, and physical exam scored 0-12), annualized bleeding rates (ABRs) by disease severity, and adverse events (AEs). Findings reported here are from the 6-year interim analysis (data cut-off: July 15, 2019), and focus on patients who have received rAHF prophylaxis or on-demand (OD) treatment for ≥5 years in the studies. All data are reported for the safety analysis set (SAS), which comprised patients who passed screening and were assigned to a treatment group or regimen in the INT study, or were enrolled and have received ≥1 dose of rAHF since study enrollment in the GER study. Results: At the time of analysis, the INT study SAS comprised 707 patients, 156 of whom had received ≥5 years of rAHF treatment during the study. The GER study SAS comprised 382 patients, 231 of whom had received ≥5 years of rAHF treatment. Average Gilbert scores (all joints) were consistently low (years 1-6: median 0-1.0; mean 0-1.3) for both children aged 2 to &lt;12 years and adolescents aged 12 to &lt;18 years receiving rAHF prophylaxis within both studies. In the INT study, average Gilbert scores were lower with prophylaxis than with OD therapy in adults (aged ≥18 years) throughout the observation period (years 1-6: median: 0.9-1.4 [n=8-25] vs 1.4-6.3 [n=2-8], respectively; mean: 1.4-2.2 vs 2.1-6.3; respectively); significant differences (P&lt;0.05) between mean values were observed for years 3, 4, and 6. In the GER study, average Gilbert scores were slightly higher with prophylaxis than with OD in adults (years 1-6: median: 0.7-2.2 [n=12-37] vs 0.3-1.4 [n=2-15], respectively; mean: 1.0-2.7 vs 0.5-2.2, respectively; P-values not available). In the INT study, ABRs were consistently lower in patients receiving rAHF prophylaxis than in those receiving rAHF OD, irrespective of disease severity (Table). A similar trend was observed in the GER study in patients with severe HA, whereas ABRs were similar for both treatment regimens in patients with moderate HA. In both studies, greater proportions of patients with moderate or severe HA receiving rAHF prophylaxis had 0 bleeds than those receiving rAHF OD (Table). In the INT study, 842 AEs were reported in 116/156 (74.4%) patients, including 2 treatment-related serious AEs in 2 (1.3%) patients. In the GER study, 1321 AEs were reported in 197/231 (85.3%) patients, including 29 treatment-related serious AEs in 14 (6.1%) patients. Conclusions: These findings in patients receiving rAHF for ≥5 years in a real-world setting corroborate previous data on the long-term efficacy and tolerability of rAHF in patients with moderate or severe HA. rAHF demonstrated effectiveness in maintaining joint health (as measured by Gilbert scores) in adult patients. Table Disclosures Tsakiris: Roche: Research Funding; Shire, a Takeda company: Research Funding; Sobi: Research Funding; Bayer: Research Funding; CSL Behring: Research Funding; Novo Nordisk: Research Funding; Pfizer: Research Funding; Octapharma: Research Funding. Oldenburg:Sobi: Consultancy, Speakers Bureau; Bayer: Consultancy, Research Funding, Speakers Bureau; Biotest: Consultancy, Research Funding, Speakers Bureau; CSL Behring: Consultancy, Research Funding, Speakers Bureau; Novo Nordisk: Consultancy, Research Funding, Speakers Bureau; Octapharma: Consultancy, Research Funding, Speakers Bureau; Pfizer: Consultancy, Research Funding, Speakers Bureau; Shire, a Takeda company: Consultancy, Research Funding, Speakers Bureau; Biogen: Consultancy, Speakers Bureau; Chugai: Consultancy, Speakers Bureau; Grifols: Consultancy, Speakers Bureau; Roche: Consultancy, Speakers Bureau. Klamroth:Pfizer: Consultancy, Research Funding, Speakers Bureau; Biotest: Speakers Bureau; Grifols: Speakers Bureau; Takeda/Shire: Consultancy, Research Funding, Speakers Bureau; Octapharma: Consultancy, Research Funding, Speakers Bureau; Novo Nordisk: Consultancy, Research Funding, Speakers Bureau; Biomarin: Consultancy, Research Funding, Speakers Bureau; CSL Behring: Research Funding, Speakers Bureau; Roche: Consultancy, Speakers Bureau; Sobi: Consultancy, Speakers Bureau; Bayer: Consultancy, Research Funding, Speakers Bureau. Guillet:CSL Behring: Research Funding, Speakers Bureau; Octapharma: Research Funding; Bayer: Consultancy; Novo Nordisk: Consultancy, Speakers Bureau; Shire, a Takeda company: Consultancy, Speakers Bureau; Roche-Chugai: Consultancy, Speakers Bureau. Khair:Shire, a Takeda company: Consultancy, Speakers Bureau; Novo Nordisk: Consultancy, Research Funding, Speakers Bureau; Pfizer: Research Funding, Speakers Bureau; Roche: Consultancy, Speakers Bureau; Sobi: Consultancy, Research Funding, Speakers Bureau; Bayer: Consultancy, Speakers Bureau; Baxalta/Shire, Takeda companies: Research Funding. Huth-Kühne:Bayer: Consultancy; CSL Behring: Consultancy; Shire, a Takeda company: Consultancy; Sobi: Consultancy. Kurnik:Sobi: Consultancy, Research Funding; Biotest: Consultancy, Speakers Bureau; Bayer: Consultancy, Research Funding, Speakers Bureau; CSL Behring: Consultancy, Research Funding, Speakers Bureau; Novo Nordisk: Consultancy, Research Funding, Speakers Bureau; Pfizer: Research Funding; Roche: Consultancy, Research Funding, Speakers Bureau; Shire, a Takeda company: Consultancy, Research Funding, Speakers Bureau. Regensburger:Takeda Pharma Vertrieb GmbH & Co. KG: Current Employment, Current equity holder in publicly-traded company. Botha:Takeda Pharmaceutical International AG: Current Employment, Current equity holder in publicly-traded company. Fernandez:Takeda Pharmaceutical International AG: Current Employment, Current equity holder in publicly-traded company. Tang:Takeda Pharmaceutical International AG: Current Employment, Current equity holder in publicly-traded company. Ozelo:Pfizer: Consultancy, Research Funding; Shire/Takeda: Consultancy, Research Funding, Speakers Bureau; Roche: Consultancy, Research Funding, Speakers Bureau; Bioverativ/Sanofi: Consultancy, Research Funding; BioMarin: Consultancy, Research Funding, Speakers Bureau; Novo Nordisk: Consultancy, Research Funding, Speakers Bureau.

AB0301 SARILUMAB AS MONOTHERAPY OR IN COMBINATION WITH CONVENTIONAL SYNTHETIC DMARDS IN PATIENTS WITH RHEUMATOID ARTHRITIS: 12-WEEK TREATMENT RESULTS FROM A MULTICENTER, OPEN-LABEL, PROSPECTIVE, SINGLE-ARM OBSERVATIONAL STUDY

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1450.1-1450
Author(s):  
A. Kivitz ◽  
J. E. Gottenberg ◽  
M. Bergman ◽  
M. Iglesias-Rodriguez ◽  
G. St John ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Clinical Practice ◽  
Combination Therapy ◽  
Observational Study ◽  
Interim Analysis ◽  
Routine Clinical Practice ◽  
Efficacy And Safety ◽  
Research Support ◽  
Open Label ◽  
Synthetic Dmards

Background:Due to strict inclusion/exclusion criteria, randomized controlled trials (RCTs) may not represent the heterogeneous rheumatoid arthritis (RA) population encountered in routine clinical practice; longitudinal observational studies are needed to complement learnings from RCTs. The PROspective sarilumab (preFILled syringe/pen) multinational, obsErvational Study (PROFILE) is collecting information on treatment strategies and sarilumab usage patterns and adherence in routine clinical practice for up to 52 weeks in patients with moderate-to-severe RA.Objectives:In this planned interim analysis, we report baseline characteristics of patients prescribed sarilumab in routine clinical practice and the efficacy and safety of sarilumab after 12 weeks of treatment.Methods:Adults with RA (2010 ACR/EULAR criteria) can enroll in this multinational, open-label, single-arm, Phase 4 study if, per their treating physicians’ judgment, they are to initiate treatment with sarilumab as mono- or combination (with csDMARD) therapy, in accordance with local labeling/prescribing information, ≤4 weeks prior to or ≤8 weeks after study Visit 1 (signed informed consent and disease characteristics documented); 1000 patients are planned for enrollment. Concomitant use of biologic or targeted synthetic DMARDs (b/tsDMARDs) is not permitted. Primary endpoint is change from baseline in Clinical Disease Activity Index (CDAI) score at Weeks 24 and 52. Statistical analyses are descriptive.Results:This analysis included 291 patients who reached, or discontinued before, the Week 12 visit, of whom 108 (37%) received sarilumab mono- and 183 (63%) received combination therapy. At baseline (BL), the monotherapy group had longer disease duration and a smaller proportion of b/tsDMARD-naïve patients than the combination therapy group (9.7 vs 8.7 years and 39% vs 53%). Baseline and week 12 CDAI values were available in 132 patients. Mean (SD) BL CDAI scores for the monotherapy and combination groups were 26.7 (13.1) and 27.0 (14.4). At Week 12, CDAI scores were improved by −9.1 (17.5) and −10.5 (13.9), and 37% (19/51) of patients receiving monotherapy and 48% (45/93) of those receiving combination therapy had achieved low disease activity (CDAI ≤10). Remission (CDAI ≤2.8) was achieved by 12% (6/51) of monotherapy and 20% (19/93) of combination-therapy patients. Overall, 55 (19%) discontinued sarilumab: 27 (9%) for an adverse event (AE), 19 (7%) for insufficient response, 4 (1%) for noncompliance, 5 (2%) for other reasons. Severe AEs leading to treatment discontinuation were leukopenia and neutropenia (n=1 patient), peripheral swelling (1), lung cancer (1), and fatigue (1). Ten patients (3%) had a treatment-emergent serious AE.Conclusion:In this planned interim analysis, sarilumab mono- or combination therapy resulted in improved disease outcomes, assessed by CDAI, at Week 12, an important treat-to-target time point. Safety and efficacy were consistent with Phase 3 trial findings, with no new safety signals, although interim results must be interpreted with caution. Future analyses will evaluate efficacy and safety after 24 and 52 weeks of treatment in routine clinical practice.Acknowledgments:Study funding and medical writing support (Laura George, Adelphi Communications Ltd, Macclesfield, UK) were provided by Sanofi Genzyme (Cambridge, USA) and Regeneron Pharmaceuticals, Inc. (Tarrytown, USA) in accordance with Good Publication Practice (GPP3) guidelines.Disclosure of Interests:Alan Kivitz Shareholder of: AbbVie, Amgen, Gilead, GSK, Pfizer Inc, Sanofi, Consultant of: AbbVie, Boehringer Ingelheim,,Flexion, Genzyme, Gilead, Janssen, Novartis, Pfizer Inc, Regeneron, Sanofi, SUN Pharma Advanced Research, UCB, Paid instructor for: Celgene, Genzyme, Horizon, Merck, Novartis, Pfizer, Regeneron, Sanofi, Speakers bureau: AbbVie, Celgene, Flexion, Genzyme, Horizon, Merck, Novartis, Pfizer Inc, Regeneron, Sanofi, Jacques-Eric Gottenberg Grant/research support from: Bristol-Myers Squibb, Pfizer, Roche, Consultant of: AbbVie, Bristol-Myers Squibb, Janssen, Lilly, MSD, Pfizer, Roche, UCB, Speakers bureau: AbbVie, Bristol-Myers Squibb, Gilead, Janssen, Lilly, MSD, Pfizer, Roche, UCB, Martin Bergman Shareholder of: Johnson & Johnson – stockholder, Consultant of: AbbVie, BMS, Celgene Corporation, Genentech, Janssen, Merck, Novartis, Pfizer, Sanofi – consultant, Speakers bureau: AbbVie, Celgene Corporation, Novartis, Pfizer, Sanofi – speakers bureau, Melitza Iglesias-Rodriguez Shareholder of: Sanofi Genzyme, Employee of: Sanofi Genzyme, Gregory St John Shareholder of: Regeneron Pharmaceuticals, Inc., Employee of: Regeneron Pharmaceuticals, Inc., Chunfu Qiu Shareholder of: Sanofi Genzyme, Employee of: Sanofi Genzyme, Hubert van Hoogstraten Shareholder of: Sanofi, Employee of: Sanofi, Louis Bessette Grant/research support from: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Merck, Novartis, Pfizer, Roche, Sanofi, UCB Pharma, Consultant of: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Merck, Novartis, Pfizer, Roche, Sanofi, UCB Pharma, Speakers bureau: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Merck, Novartis, Pfizer, Sanofi

Predictors for survival with cabazitaxel (CBZ) in metastatic, castration-resistant prostate cancer (mCRPC): Long term follow-up of the Spanish registry.

2017 ◽  
Vol 35 (6_suppl) ◽  
pp. e602-e602
Author(s):  
Iria González-Maeso ◽  
Nuria Lainez ◽  
Daniel Castellano ◽  
Iciar Garcia Carbonero ◽  
Pablo Borrega ◽  
...  
Keyword(s):  
Progression Free Survival ◽  
Therapeutic Benefit ◽  
Castration Resistant Prostate Cancer ◽  
First Line ◽  
Castration Resistant ◽  
Long Term Follow Up ◽  
Baseline Characteristics ◽  
Grade 3

e602 Background: The clinical experience with CBZ in mCRPC patients (pts) has enriched notably since its approval for clinical use, but there is still a lack of well-defined prognostic/predictive factors to better characterize the profile of pts that could achieve the best therapeutic benefit. Analysis of the final expanded cohort and mature long-term follow-up are presented. Methods: Medical records from mCRPC pts progressing during or after docetaxel and treated with CBZ at 21 centres in Spain were reviewed retrospectively. Baseline characteristics, overall survival (OS), radiographic progression-free survival (rPFS), and toxicity were collected. Univariate and multivariate analysis of a variety of factors predicting OS were conducted. Results: 187 consecutive pts (median age 69) with intermediate-poor prognostic baseline characteristics (Table 1) received a median of 6 cycles (range 2-59) of CBZ. Median OS from first CBZ cycle was 15.3 [CI: 11.7; 18.0] months (mo) and median clinical and/or rPFS was 7.9 mo [CI: 6.8; 10.3]. Gleason score (GS) < 8 (vs ≥ 8), time under first-line androgen deprivation therapy (ADT) ( > 16.1 (median) vs < 16.1 mo) and the number of chemotherapy lines before CBZ did not significantly influence OS. Median follow-up was 9.5 mo. Febrile neutropenia occurred in 4 pts and 1 pt had neutropenic infection. Main nonhematologic grade ≥ 3 toxicities were asthenia (2.7%) and diarrhea (1.6%). Alopecia, nails disorders and peripheral neuropathy were uncommon. Conclusions: CBZ administered in the daily clinical practice is associated with consistent OS, similar to that observed in pivotal clinical trials. GS, median time under first-line ADT and number of chemotherapy lines before CBZ did not influence clinical benefit. CBZ has an acceptable safety profile. Funding: Sanofi [Table: see text]

Incidence of hypocalcemia in patients with castration-resistant prostate cancer treated with denosumab: Data from a non-inferiority phase III trial assessing prevention of symptomatic skeletal events (SSE) with denosumab administered every four weeks (q4w) versus every 12 weeks (q12w)—SAKK 96/12 (REDUSE).

2019 ◽  
Vol 37 (7_suppl) ◽  
pp. 139-139 ◽  
Author(s):  
Silke Gillessen ◽  
Roger Anton Fredy Von Moos ◽  
Stefanie Hayoz ◽  
Hanne Hawle ◽  
Richard Cathomas ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Interim Analysis ◽  
Phase Iii ◽  
Induction Treatment ◽  
Induction Phase ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Long Time ◽  
Skeletal Related Events ◽  
Grade 3

139 Background: DN given q4w has shown superiority in delaying skeletal related events over q4w zoledronic acid (ZA). Recently it has been demonstrated that ZA q12w is non-inferior to ZA q4w. The objective of REDUSE is to show non-inferiority for DN q12w versus q4w in terms of SSE. Here we present an interim analysis for the secondary endpoint HC. Methods: Patients (pts) with castration resistant prostate cancer (planned N=690) were randomized 1:1 to DN q4w (Arm A) vs q12w (Arm B) after a 16 week induction phase with application q4w. All pts received vitamin D (ViD) 400 U and calcium (Ca) 500 mg daily. Measurement of corrected serum-Ca was mandatory before each DN injection. This interim analysis was performed after 3.5 years of accrual. Men who received ≥ 1 dose of DN were considered evaluable. Results: 383 pts were evaluable. HC occurred in 28.7% during the first 16 weeks (DN q4w for all pts) and 30.2% afterwards. After the induction phase HC occurred in 40.2% in Arm A and in 20.3% in Arm B. Grade 3 (2.1%) and 4 (1.1%) HC were rare, most frequently occurring in the first 16 weeks. After 1 year of treatment, the incidence of HC was lower in both arms (A: 30.8%, B: 18.7%). A clinically relevant difference for HC was noted between the two arms after the induction phase (table). Conclusions: In our trial nearly 30% of all men treated with DN experienced HC in the q4w induction phase despite mandatory supplementation of calcium and ViD and measurement of Ca. This rate was considerably higher than reported in the registration trials of DN (13%). After induction treatment the incidence of HC is considerably lower in the q12w arm compared to q4w. This suggests that DN given q12w has a more favorable long time toxicity profile (HC) compared to DN q4w. Change in HC grade after week 16 (week 1 – 12: DN q4w Arm A+B), thereafter q4w in Arm A and q12w in Arm B. Clinical trial information: NCT02051218. [Table: see text]

Safety and overall survival (OS) in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) treated with radium-223 (Ra-223) plus subsequent taxane therapy.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 5542-5542
Author(s):  
Celestia S. Higano ◽  
Lauren C Harshman ◽  
Sabina Dizdarevic ◽  
John Logue ◽  
Timothy Richardson ◽  
...  
Keyword(s):  
Clinical Practice ◽  
Analysis Data ◽  
Routine Clinical Practice ◽  
Treatment Modalities ◽  
Castration Resistant Prostate Cancer ◽  
Primary Tumors ◽  
Multiple Treatment ◽  
Radium 223 ◽  
Grade 3

5542 Background: Ra-223, a targeted alpha therapy, showed a survival benefit and favorable safety profile over 3 years’ (yrs) follow-up in mCRPC pts (ALSYMPCA trial). REASSURE (NCT02141438) is a global, prospective, single-arm, observational study of long-term Ra-223 safety in routine clinical practice in mCRPC pts (planned 7-yr follow-up). Methods: This analysis, based on the second prespecified interim analysis (data cutoff 3-20-2019) of REASSURE (N = 1465), evaluated safety/OS in the pt subset that was chemotherapy-naïve at Ra-223 administration but received subsequent taxane therapy any time after Ra-223 completion. Results: 182 pts received taxane therapy after Ra-223. Most (58%) had unresected primary tumors, 69% had ≥6 metastases, 99% received prior systemic anticancer therapy (Table). 143 (79%) completed 5 or 6 Ra-223 injections. Subsequent anticancer therapies included docetaxel (95%), enzalutamide (25%), cabazitaxel (24%), abiraterone (12%), lutetium-177-prostate-specific membrane antigen (4%), and sipuleucel-T (1%). During/up to 30 days after taxane therapy, 15 pts (8%) had grade 3/4 hematologic adverse events: anemia (erythropenia) (n = 11, 6%), neutropenia (n = 3, 2%), and thrombocytopenia (n = 2, 1%). Median OS was 24.3 (95% CI: 20.9–27.5) months from Ra-223 initiation and 11.8 (95% CI: 10.6–14.1) months from subsequent taxane initiation. Conclusions: In this cohort where Ra-223 was integrated prior to taxane therapy, most pts received multiple subsequent anticancer therapies. It appears that sequencing of multiple treatment modalities with different mechanisms of action may contribute to improved OS. Taxane therapy in routine clinical practice in pts previously treated with Ra-223 had acceptable hematologic safety/tolerability profiles. Clinical trial information: NCT02141438 . [Table: see text]

Sign in / Sign up

Export Citation Format

Share Document