scholarly journals Genomic alterations in circulating tumor DNA (ctDNA) are associated with clinical outcomes in treatment-naive metastatic castration-resistant prostate cancer (mCRPC) patients commencing androgen receptor (AR)-targeted therapy

2016 ◽  
Vol 27 ◽  
pp. vi17 ◽  
Author(s):  
A.W. Wyatt ◽  
M. Annala ◽  
K. Beja ◽  
S. Parimi ◽  
G. Vandekerkhove ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Androgen Receptor ◽  
Targeted Therapy ◽  
Clinical Outcomes ◽  
Circulating Tumor Dna ◽  
Castration Resistant Prostate Cancer ◽  
Genomic Alterations ◽  
Castration Resistant ◽  
Treatment Naïve ◽  
Tumor Dna

Circulating tumor DNA (ctDNA) burden and actionable mutations in treatment-naïve metastatic castration-resistant prostate cancer (mCRPC).

2016 ◽  
Vol 34 (15_suppl) ◽  
pp. 5034-5034 ◽  
Author(s):  
Alexander William Wyatt ◽  
Matti Annala ◽  
Sunil Parimi ◽  
Muhammad Zulfiqar ◽  
Daygen L. Finch ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Circulating Tumor Dna ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Treatment Naïve ◽  
Tumor Dna

scholarly journals Treatment Sequences of Androgen Receptor–Targeted Agents for Prostate Cancer

2021 ◽  
Vol 1 (3) ◽  
Author(s):  
Khai Tran ◽  
Sarah McGill
Keyword(s):  
Prostate Cancer ◽  
Retrospective Study ◽  
Androgen Receptor ◽  
Clinical Outcomes ◽  
Progression Free Survival ◽  
Targeted Agents ◽  
Castration Resistant Prostate Cancer ◽  
Free Survival ◽  
Castration Resistant ◽  
Treatment Sequences

No evidence was found on the treatment sequences of androgen receptor–targeted agents in patients with castration-sensitive prostate cancer. Evidence from retrospective studies, including those within a systematic review, suggests that sequential treatment of abiraterone followed by enzalutamide is more favourable than enzalutamide followed by abiraterone in improving clinical outcomes such as response rate and progression-free survival, but not overall survival, in patients with castration-resistant prostate cancer. Evidence from a retrospective study suggests that docetaxel-containing treatment sequences with androgen receptor–targeted agents may improve progression-free survival compared to sequential therapy with androgen receptor–targeted agents alone in patients with castration-resistant prostate cancer. Evidence from a retrospective study did not reveal differences in clinical outcomes of patients with castration-resistant prostate cancer treated with sequential androgen receptor–targeted agents with or without interposed chemotherapy or radium-223. These findings were in line with those observed in a 2019 CADTH report.1 However, the findings should be interpreted with caution due to low-quality evidence. No comparative cost-effectiveness studies were identified.

Germline DNA repair mutations in metastatic castration-resistant prostate cancer: Therapy response and applicability of circulating tumor DNA.

2017 ◽  
Vol 35 (6_suppl) ◽  
pp. 140-140 ◽  
Author(s):  
Werner J. Struss ◽  
Matti Annala ◽  
Evan W Warner ◽  
Kevin Beja ◽  
Gillian Vandekerkhove ◽  
...  
Keyword(s):  
Dna Repair ◽  
Targeted Therapy ◽  
Gene Loss ◽  
Germline Mutations ◽  
Circulating Tumor Dna ◽  
Dna Repair Genes ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Repair Genes ◽  
Tumor Dna

140 Background: Germline mutations in DNA repair genes were recently reported in 8-12% of patients with metastatic castration-resistant prostate cancer (mCRPC). It is unknown whether these mutations associate with differential response to Androgen Receptor (AR) targeted therapy. The aim of this study was to determine the clinical response of mCRPC patients with germline DNA repair defects to AR-directed therapies, and secondly to establish whether biallelic DNA-repair gene loss is detectable in matched circulating tumor DNA (ctDNA). Methods: We recruited 319 mCRPC patients and performed targeted germline sequencing of 22 DNA repair genes. In affected patients, matched plasma ctDNA was also sequenced. Prostate-specific antigen response and progression were assessed in relation to initial androgen deprivation therapy (ADT) and subsequent therapy for mCRPC using Kaplan-Meier analysis. Results: 24/319 (7.5%) patients had deleterious germline mutations, with BRCA2 (n = 16), PALB2 (n = 2) and CDK12 (n = 2) being the most frequent. Patients (n = 22) with mutations in genes linked to homologous recombination were heterogeneous at initial presentation but after starting ADT progressed to mCRPC with a median time of 12.3 months (95% CI 5.1-18.4). The median time to progression on first and second line AR-targeted therapy in the mCRPC setting was 3.2 months (95% CI 1.9-4.4) and 1.0 month (95% CI 0.8-1.1), respectively. For patients receiving chemotherapy as their initial therapy for mCRPC (n = 8) the median PFS was 7.5 months (95% CI 6.5-8.2). 10/11 evaluable patients with germline BRCA2 mutations had somatic deletion of the intact allele in ctDNA. Conclusions: mCRPC patients with germline DNA repair defects exhibit transient responses to AR-targeted therapy. Biallelic gene loss was robustly detected in ctDNA suggesting that this patient subset could be prioritized for therapies exploiting defective DNA repair using a liquid biopsy.

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