Real world patterns of treatment sequencing in Canada for metastatic castrate-resistant prostate cancer.

2018 ◽  
Vol 36 (6_suppl) ◽  
pp. 320-320
Author(s):  
Sebastien J. Hotte ◽  
Antonio Finelli ◽  
Shawn Malone ◽  
Bobby Shayegan ◽  
Alan I. So ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Targeted Therapy ◽  
Best Practices ◽  
Real World ◽  
Advanced Prostate Cancer ◽  
First Line ◽  
Online Questionnaire ◽  
Physician Practices ◽  
Research Education ◽  
Treatment Sequencing

320 Background: The Canadian GU Research Consortium (GURC) was recently established to bring advanced prostate cancer centres together to collaborate on research, education, and adoption of best practices. As an initial step to inform the work of the GURC, an electronic questionnaire was designed to assess management of advanced prostate cancer care in Canada and how prostate cancer treatments are sequenced in a real-world setting. Methods: A 59-item online questionnaire was developed by a multidisciplinary scientific committee to measure physician practices, patterns of care, treatment sequencing, and management of mCRPC. After pre-testing, the online questionnaire was sent to 93 urologists, uro-oncologists, medical oncologists, radiation oncologists, and general practitioner oncologists who are actively involved in the treatment of prostate cancer. Results: A total of 49 (53%) respondents completed the questionnaire between April 17, 2017 to May 17, 2017. Based on physician reports, the most frequently used treatment for first-line mCRPC was AR-targeted therapy (94%, n = 46 physicians) such as abiraterone acetate plus prednisone and enzalutamide. Among those 46 physicians, AR-targeted therapy was usually followed by docetaxel second-line therapy (57%, 31 physicians). The most common line 1 to line 3 treatment sequence for mCRPC was: AR-targeted therapy--Docetaxel--AR-targeted therapy (35%, 17 physicians), followed by AR-targeted therapy--Docetaxel--Radium 223 (14%, n = 7), Provincial differences were observed in the line 1 to line 3 treatment sequences, which aligned to variation in provincial policies for access to the treatments. In patients previously treated with docetaxel in the hormone sensitive setting, the most frequently used treatment for first-line mCRPC was AR-targeted therapy (76%, 37 physicians). Conclusions: AR targeted therapy followed by docetaxel is the predominant pattern of practice for management of mCRPC, with variability beyond these lines of therapy. Prospective ongoing work through the GURC in research, education and best practices will aim to understand these practice patterns.

Outcomes in patients (Pts) with advanced prostate cancer and inactivating germline mutations in BRCA2 or ATM.

2018 ◽  
Vol 36 (6_suppl) ◽  
pp. 242-242 ◽  
Author(s):  
Steven Yip ◽  
Daniel Khalaf ◽  
Werner J. Struss ◽  
Katherine Sunderland ◽  
Gillian Vandekerkhove ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Targeted Therapy ◽  
Median Time ◽  
Advanced Prostate Cancer ◽  
Germline Mutations ◽  
Rank Test ◽  
Castration Resistant Prostate Cancer ◽  
First Line ◽  
Available N ◽  
Atm Gene

242 Background: Germline mutations in homologous recombination repair (HRR) genes, including BRCA2, are present in 6-12% of pts with metastatic castration-resistant prostate cancer (mCRPC). BRCA2 germline mutations are associated with high-grade and poor-prognosis localized disease, while outcomes in pts with advanced prostate cancer continue to be defined. Methods: Germline DNA from 536 consecutive mCRPC pts in our liquid biopsy program were screened for BRCA2 and ATM gene mutations using targeted sequencing. Kaplan-Meier curves were used to estimate the median time from androgen deprivation therapy (ADT) initiation to mCRPC, progression free survival (PFS) on first-line androgen receptor (AR) targeted therapy, and overall survival (OS). Outcomes in BRCA2 or ATM germline mutation carriers and a subset of the total sample of HRR wild-type (WT) pts, who had clinical data available (n = 113), were compared using the log-rank test. Results: 26/536 (4.9%) of pts had germline BRCA2 (n = 22) or ATM mutations (n = 4). After ADT initiation, HRR mutated pts progressed to mCRPC with a median time of 13.4 mo compared to 19.0 mo in WT pts (HR = 1.6, [95% CI 1.0-2.5], p = 0.03). HRR mutated pts had a median PFS on first-line AR-targeted therapy in the mCRPC setting of 3.3 mo versus 7.9 mo in WT pts (HR = 2.2, [95% CI 1.3-3.5], p = 0.002). OS for HRR mutated pts from the time of ADT was 57.7 mo in contrast to 104.9 mo in WT pts (HR = 1.8, [95% CI 1.0-3.4], p = 0.07). OS from time of CRPC was 29.7 mo in HRR mutated pts versus 50.3 mo in WT pts (1.6, [95% CI 0.8-2.9], p = 0.16). Conclusions: Germline HRR mutated pts perform poorly with shorter PFS on first-line AR-targeted therapy and time to mCRPC, in contrast to WT pts. These findings support the hypothesis that BRCA2 and ATM gene mutated pts have poor outcomes with current AR-targeted treatments and should be evaluated for alternate regimens.

scholarly journals A A Canadian consensus forum on the management of patients with advanced prostate cancer

2019 ◽  
Vol 14 (4) ◽  
Author(s):  
Fred Saad ◽  
Christina Canil ◽  
Antonio Finelli ◽  
Sebastien J. Hotte ◽  
Shawn Malone ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Advanced Prostate Cancer ◽  
Castration Resistant Prostate Cancer ◽  
Research Education ◽  
Modified Delphi ◽  
Castration Resistant ◽  
Medical Oncologists ◽  
Oligometastatic Prostate Cancer ◽  
Scientific Group ◽  
High Level

Introduction: The management of advanced prostate cancer (PCa) continues to evolve with the emergence of new diagnostic and therapeutic strategies. As a result, there are multiple areas in this landscape with a lack of high-level evidence to guide practice. Consensus initiatives are an approach to establishing practice guidance in areas where evidence is unclear. We conducted a Canadian-based consensus forum to address key controversial areas in the management of advanced PCa. Methods: As part of a modified Delphi process, a core scientific group of PCa physicians (n=8) identified controversial areas for discussion and developed an initial set of questions, which were then reviewed and finalized with a larger group of 29 multidisciplinary PCa specialists. The main areas of focus were non-metastatic castration-resistant prostate cancer (nmCRPC), metastatic castration-sensitive prostate cancer (mCSPC), metastatic castration-resistant prostate cancer (mCRPC), oligometastatic prostate cancer, genetic testing in prostate cancer, and imaging in advanced prostate cancer. The predetermined threshold for consensus was set at 74% (agreement from 20 of 27 participating physicians). Results: Consensus participants included uro-oncologists (n=13), medical oncologists (n=10), and radiation oncologists (n=4). Of the 64 questions, consensus was reached in 30 questions (n=5 unanimously). Consensus was more common for questions related to biochemical recurrence, sequencing of therapies, and mCRPC. Conclusions: A Canadian consensus forum in PCa identified areas of agreement in nearly 50% of questions discussed. Areas of variability may represent opportunities for further research, education, and sharing of best practices. These findings reinforce the value of multidisciplinary consensus initiatives to optimize patient care.

scholarly journals Experience with degarelix in the treatment of prostate cancer

2012 ◽  
Vol 5 (1) ◽  
pp. 11-24 ◽  
Author(s):  
Neal D. Shore
Keyword(s):  
Prostate Cancer ◽  
Gnrh Agonist ◽  
Clinical Studies ◽  
Advanced Prostate Cancer ◽  
Gnrh Antagonist ◽  
Serum Alkaline Phosphatase ◽  
Specific Antigen ◽  
Progression Free Survival ◽  
Similar Efficacy ◽  
First Line

Degarelix is a gonadotrophin-releasing hormone (GnRH) antagonist for the first-line treatment of androgen-dependent advanced prostate cancer. It has a direct mechanism of action that blocks the action of GnRH on the pituitary with no initial surge in gonadotrophin or testosterone levels. Degarelix is the most extensively studied and widely available GnRH antagonist worldwide. Clinical studies have demonstrated similar efficacy to the GnRH agonist leuprolide in achieving testosterone suppression in patients with prostate cancer. However, degarelix produces a faster suppression of testosterone and prostate-specific antigen (PSA), with no testosterone surge or microsurges, thus preventing the risk of clinical flare in advanced disease. Clinical trials have demonstrated that degarelix can offer improved disease control when compared with a GnRH agonist in terms of superior PSA progression-free survival (suggesting that degarelix likely delays progression to castration-resistant disease), and a more significant impact on bone serum alkaline phosphatase and follicle-stimulating hormone. Degarelix is generally well tolerated, with no reports of systemic allergic reactions in any clinical studies. In conclusion, degarelix offers clinicians a rational first-line hormonal monotherapy option for the management of advanced prostate cancer.

Treatment sequencing patterns of novel agents in patients with prostate cancer.

2014 ◽  
Vol 32 (30_suppl) ◽  
pp. 296-296 ◽  
Author(s):  
Elisabetta Malangone ◽  
Kathleen A. Foley ◽  
Kathleen Wilson ◽  
Helen Varker ◽  
Alison Binder ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Index Date ◽  
Data Availability ◽  
Second Line ◽  
Castration Resistant Prostate Cancer ◽  
First Line ◽  
Nccn Guidelines ◽  
Study Results ◽  
Treatment Sequencing ◽  
Line Of Therapy

296 Background: The National Comprehensive Cancer Network (NCCN) guidelines recommend chemotherapy, immunotherapy or anti-androgen therapies for the treatment of advanced castration-resistant prostate cancer (CRPC). This study evaluated treatment sequencing of recently approved agents for CRPC [abiraterone (ABI), enzalutamide (ENZ), docetaxel (DOC), cabazitaxel (CAB), or sipuleucel-T (SIP)] among men with PC. Methods: This retrospective, observational study evaluated adult men with PC in the MarketScan Oncology EMR database, which includes data from over 900 contributing oncologists from over 100 community practices. Inclusion required a diagnosis of PC (ICD-9-CM diagnosis code 185) from 07/01/2011-03/31/2014, no treatment with ABI, ENZ, DOC, CAB, or SIP prior to 09/01/2012, no other primary cancers, and six months of medical record history prior to index date. The index date was the date of first prescription of ABI, ENZ, DOC, CAB or SIP between 09/01/2012 and 03/31/2014. First-, second- and subsequent-line treatments were evaluated prior to end of data availability or end of study. Results: In total, 812 PC patients were identified; mean age was 75 years and 68% had recorded metastasis. A single line of therapy was observed for 544 patients (67%). ABI was the most common first-line treatment (443; 55%), followed by DOC (167; 21%), ENZ (113; 14%), SIP (82; 10%) and CAB (7; 1%). A second line of therapy occurred in 268 patients (33%) and third line in 8%. The table below describes first-line and the two most common second-line therapies for those moving on to second-line. Conclusions: Of the five agents of interest, ABI was the most commonly prescribed first-line medication for advanced PC in this patient cohort. First-line DOC was more common than first-line CAB or SIP. Further studies with longer follow-up and other treatments are warranted. [Table: see text]

Real-world outcomes in first-line treatment of metastatic castration-resistant prostate cancer (mCRPC): The prostate cancer registry.

2017 ◽  
Vol 35 (6_suppl) ◽  
pp. 212-212 ◽  
Author(s):  
Simon Chowdhury ◽  
Alison J. Birtle ◽  
Anders Bjartell ◽  
Luis Costa ◽  
Susan Feyerabend ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Registry ◽  
Real World ◽  
Severe Disease ◽  
Specific Antigen ◽  
Abiraterone Acetate ◽  
Castration Resistant Prostate Cancer ◽  
First Line ◽  
Psa Response ◽  
Baseline Characteristics

212 Background: The Prostate Cancer Registry is the first prospective, international observational study in mCRPC documenting characteristics and management in routine clinical practice, independent of treatment used. The study began in June 2013 enrolling > 3000 mCRPC patients (pts) followed for ≤ 3 years. Methods: Source-verified data were collected from men with documented mCRPC initiating a new mCRPC treatment or in surveillance. A history of disease progression despite surgical or chemical ADT was confirmed in all pts. This interim analysis reports baseline characteristics, treatments and outcomes in pts with no prior mCRPC treatment. To evaluate comparative effectiveness between treatments, propensity scoring (PS) methods were used to reduce effects of confounding. Results: Of 1906 evaluable pts with ≥ 12-month follow-up, the most commonly initiated first-line mCPRC treatments (n ≥ 50) were abiraterone acetate + prednisone (AA, n = 472), enzalutamide (ENZ, n = 98) or docetaxel (DOC, n = 382). Baseline characteristics, time to progression (TTP) and prostate-specific antigen (PSA) response ( ≥ 50% decrease within 6 months) are shown in the table below. Conclusions: In this real-world study, pts receiving DOC as their first mCRPC treatment had more severe disease at entry and a trend for shorter TTP vs androgen inhibitors. TTP results are consistent with those in randomised clinical trials for AA and ENZ. Clinical trial information: NCT02236637. [Table: see text]

Patterns of prostate cancer management across Canadian prostate cancer treatment specialists.

2018 ◽  
Vol 36 (6_suppl) ◽  
pp. 321-321
Author(s):  
Bobby Shayegan ◽  
Alan I. So ◽  
Shawn Malone ◽  
Sebastien J. Hotte ◽  
Antonio Finelli ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Treatment ◽  
Advanced Prostate Cancer ◽  
Patterns Of Care ◽  
Online Questionnaire ◽  
Prostate Cancer Treatment ◽  
Chi Square ◽  
Cancer Management ◽  
Radiation Oncologists ◽  
Medical Oncologists

321 Background: The Canadian GU Research Consortium (GURC) was recently established to bring comprehensive prostate cancer centres together to collaborate on research, education, and adoption of best practices. As an initial step to inform the work of the GURC, an electronic questionnaire was designed to assess management of advanced prostate cancer care in Canada and better understand patterns of care. Methods: A 59-item online questionnaire was developed by a multidisciplinary scientific committee to measure physician practices, patterns of care, treatment sequencing, and management of mCRPC. After pre-testing, the online questionnaire was sent to 93 urologists, uro-oncologists, medical oncologists, radiation oncologists, and general practitioner oncologists who are actively involved in the treatment of prostate cancer. Results: A total of 49 (53%) respondents completed the questionnaire between April 17, 2017 to May 17, 2017. Although all respondents indicated a role in initiating life-prolonging oral therapy for mCRPC and monitoring treatment and side effects, chemotherapy initiation was mainly a medical oncologist role compared to other specialties (p < 0.05, chi-square). Symptom management such as palliative care and end-of-life care were provided mainly by radiation oncologists (100%) and medical oncologists (81%) compared to urologists (33%) and uro-oncologists (50%), p < 0.05, chi-square). Patient mix varied across the disciplines. Urologist practices were composed primarily of non-metastatic prostate cancer patients (73%), as were radiation oncologist practices (77%), while uro-oncologist practices included both non-metastatic (58%) and metastatic (40%) patients. Medical oncologists practices were mainly (91%) metastatic patients. Referral patterns also varied by discipline. Conclusions: In Canada, prostate cancer treatment involves multiple disciplines providing a range of care at different points across the treatment continuum. We plan to do further research to better understand variation in practice and improve multidisciplinary coordination for patients with advanced prostate cancer.

Real world experience of docetaxel in elderly patients with advanced prostate cancer.

2018 ◽  
Vol 36 (6_suppl) ◽  
pp. 313-313
Author(s):  
Simon Yuen Fai Fu ◽  
Paula Barlow ◽  
Carmel Maree Jacobs ◽  
Fritha J. Hanning ◽  
Peter C.C. Fong
Keyword(s):  
Prostate Cancer ◽  
Elderly Patients ◽  
Dose Reduction ◽  
Real World ◽  
Advanced Prostate Cancer ◽  
Dose Intensity ◽  
Admission Rate ◽  
Standard Of Care ◽  
City Hospital ◽  
Line Of Therapy

313 Background: Docetaxel (D) chemotherapy is a standard of care in men with advanced prostate cancer (APC), both metastatic castration sensitive (CS) and castration resistant (CR) disease. The risk of significant toxicities may deter D use in elderly patients. We aim to evaluate the real world efficacy and tolerability of D in men with APC. Methods: Between 04/2014 and 05/2017, data from men aged ≥75 with APC treated at Auckland City Hospital with 3 weekly D were retrospectively collected from the genitourinary medical oncology database. Results: 33 (CS 12, CR 21) men were identified. 70% had PSA decline ≥50% (CS 92%, CR 57%). Median time to next line of therapy was 0.5 y in the CR arm. One third (n = 2/6) of CR patients on opioid had improved pain control with D. 75% had upfront dose reduction (DR). The median dose intensity was 21 mg/m2/wk (CS) and 18 mg/m2/wk (CR). 9 patients had dose escalation after upfront DR, all but 3 needed DR later, and none was escalated to 75 mg/m2. 58% (CS 75%, CR 48%) completed 6 cycles, and only 6% (n = 2) completed 6 cycles at 75 mg/m2. 24% had ≥G3 hematological toxicities. Febrile neutropenia rate was 12% (CS 8%, CR 14%). Pegfilgrastim was used in 1 CS and 1 CR men. Admission rate was 39% (CS 25%, CR 48%), 77% (CS 100%, CR 70%) was treatment related, and 23% (CR 30%) due to malignancy. 15% (CS 25%, CR 9%) required RBC transfusions. 33% CR men progressed while on treatment, and two deaths from pneumonitis and disease progression were noted. Conclusions: Docetaxel is active in elderly men with APC. Toxicities are manageable but can be life-threatening. Admission is frequent especially in CR patients. Proactive dose reduction should be considered to balance benefits vs. risks in this population. [Table: see text]

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