Platinum-based therapy in men with metastatic castration resistant prostate (mCRPC) with or without DNA repair defects: A multicentre retrospective analysis

Gillessen, Silke; Schmid, Sabine; Beltran, Himisha; Almeida, Daniel Vargas Pivato de; Mehra, Niven; Lavaud, Pernelle; Barrera, Rafael; Pignataro, Daniele; Marcos, E. Castro; Conteduca, Vincenza; Efstathiou, Eleni; Le, H.M.L.; Pezaro, Carmel; Suzuki, Hiroyoshi; Zivi, Andrea; Klingbiel, Dirk; Omlin, Aurelius

doi:10.1093/annonc/mdy284.023

Cited by 4 publications

(6 citation statements)

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“…This is supported by a limited number of phase II trials and in retrospective real-world analyses to demonstrate meaningful clinical activity in mCRPC. [11][12][13][14] A phase II trial investigating the role of carboplatin and paclitaxel showed a median time to progression (TTP) of 3.6 months and mOS of 10 months. 12 However, in contrast to our study, 14 of 38 patients had received only one prior line of chemotherapy so this survival could be attributed to our patient group being more heavily pre-treated (100% had at least two prior lines of chemotherapy) and was an unselected, real-world population.…”

Section: Discussionmentioning

confidence: 99%

Beyond cabazitaxel: Late line treatments in metastatic castration resistant prostate cancer: A retrospective multicentre analysis

Chazan

Antón

Wong

et al. 2022

Asia-Pac J Clncl Oncology

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Aims Multiple life‐prolonging therapies are available for metastatic castration‐resistant prostate cancer (mCRPC). However, the optimal treatment strategy following progression through standard treatment with docetaxel, androgen receptor signaling inhibitor (ARSI) and cabazitaxel, remains unclear. We aimed to describe treatment patterns in men with mCRPC following progression on standard treatments and determine whether subsequent treatment choice impacts overall survival. Methods Clinicopathologic and treatment data were extracted from the electronic CRPC Australian Database (ePAD) for patients who had received docetaxel, ARSIs and cabazitaxel in any order. Data were analyzed to compare groups that did versus did not receive subsequent systemic therapy. Treatment sequences, median duration of treatment, and median overall survival (mOS) were reported for each treatment group. Results Ninety‐eight eligible patients were identified, with 51 receiving subsequent systemic therapy. Those who received further treatment were younger (68 vs. 71 years, p < .01) but did not have any other differences in clinicopathologic features compared to those who received no further treatment. Patients who received upfront docetaxel were more likely to proceed to subsequent treatment (p = .02). Subsequent systemic therapies varied, the most common being carboplatin‐based regimens (n = 13, 25.5%) and many patients were rechallenged with ARSI (n = 10, 19.6%) or docetaxel (n = 6, 11.8%). There was no difference in mOS according to subsequent systemic therapy (p = .09). Conclusion This retrospective multicenter analysis demonstrates the variation in treatment sequences used for mCRPC in the real‐world setting. In the absence of high quality, prospective evidence, our results suggest that subsequent treatment choice does not influence survival outcomes and the optimal choice is guided by individual patient and disease‐related factors.

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Section: Discussionmentioning

confidence: 99%

Beyond cabazitaxel: Late line treatments in metastatic castration resistant prostate cancer: A retrospective multicentre analysis

Chazan

Antón

Wong

et al. 2022

Asia-Pac J Clncl Oncology

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“…Additionally, since an exploratory gene level subgroup analysis of the OS PROFOUND data suggests that patients with ATM alterations, in contrast to other homologous recombination repair alterations, may derive less benefit with olaparib PARPi, this may be a more elegant predictive biomarker to determine which patients with ATM alterations may benefit from PARPi and show OS and PCSM survival advantage [1] . Future studies will enhance our understanding of how outcomes of patients with altered ATM and PTEN expression can be enhanced further with PARPi, combinations of PARPi and AR-targeted therapies, as well as platinum-based chemotherapies [21] , [22] .…”

Section: Discussionmentioning

confidence: 99%

Decreased ATM Protein Expression Is Substantiated with PTEN Loss in Defining Aggressive Phenotype of Prostate Cancer Associated with Lethal Disease

Walker

Abdelsalam

Ghosh

et al. 2021

European Urology Open Science

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Background Ataxia Telangiectasia Mutated (ATM) serine/threonine protein kinase is a known tumor suppressor, involved in DNA damage repair. It has prognostic and predictive therapeutic implications and is associated with aggressive prostate cancer (PCa). Objective To investigate the prognostic value of ATM protein expression in PCa patients and assessed the combined value of ATM, ERG, and PTEN status. Design, setting, and participants This study consisted of 303 patients with incidental, locally advanced, and castrate-resistant PCa by transurethral resection of the prostate (TURP). Outcome measurements and statistical analysis TURP samples from 303 PCa patients were assessed by immunohistochemistry (IHC for ATM, ERG, and PTEN. Individual and combined marker status were correlated with International Society of Urological Pathology Gleason grade group, overall survival (OS), and PCa-specific mortality (PCSM). Results and limitations Decreased ATM expression (negative/weak intensity) occurred in 164/303 (54.1%) patients, and was associated with shorter OS and higher PCSM ( p = 0.015 and p = 0.001, respectively). Negative/weak ATM expression was significantly associated with PCSM with a hazard ratio of 2.09 (95% confidence interval 1.34–3.27, p = 0.001). Assessment of Combined ATM/PTEN expression showed improved prognostic power to predict OS and PCSM, independent of Gleason grade groups. Conclusions Decreased ATM protein expression is associated with poor outcomes in advanced PCa patients. Patients with combined low ATM/PTEN negative expression are at the highest risk for reduced OS and PCSM. Assessing the combined status of ATM/PTEN by IHC in PCa patients may aid in risk stratification relative to OS and PCSM. Moreover, since ATM plays an integral role in DNA damage response pathways, future studies will enhance our understanding of how outcomes of patients with altered ATM and PTEN expression can be improved further with poly-ADP ribose polymerase inhibitors (PARPi), combinations of PARPi and androgen receptor–targeted therapies, as well as platinum-based chemotherapies. Patient summary Lower ATM intensity is associated with increased cancer-specific mortality in prostate cancer patients. Patients with lower ATM and PTEN negative expression showed decreased overall survival and increased cancer mortality compared with controls.

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“…As there is additional toxicity associated with a doublet regimen, defining those patients would be of great value in assisting clinical decisions. More work is needed to identify biomarkers of response, given that responses to carboplatin in mCRPC appear to occur independently of the presence or absence of DNA repair defects 23 …”

Section: Discussionmentioning

confidence: 99%

“…More work is needed to identify biomarkers of response, given that responses to carboplatin in mCRPC appear to occur independently of the presence or absence of DNA repair defects. 23…”

Section: Discussionmentioning

confidence: 99%

Treatment outcomes for patients with metastatic castrate‐resistant prostate cancer following docetaxel for hormone‐sensitive disease

Schmidt

Antón

Shapiro

et al. 2020

Asia-Pac J Clncl Oncology

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Aim Optimal treatment for newly diagnosed metastatic hormone‐sensitive prostate cancer (mHSPC) has evolved, with many patients deriving benefit from the addition of docetaxel to androgen deprivation therapy (D‐ADT). This study sought to define the therapy used and associated activity following D‐ADT. Methods Retrospective analysis of patients with mHSPC treated with one or more cycles of D‐ADT who were identified from a prospectively maintained multisite prostate cancer database of patients treated in a community or academic center setting in Australia. The primary endpoint of this study was first‐line time to treatment failure (1L TTF) for subsequent treatment of metastatic Castrate Resistant Prostate Cancer (mCRPC), with secondary endpoints of prostate‐specific antigen (PSA) reduction >50% and time from 1L to second‐line (2L) treatment initiation. Results A total of 93 patients received D‐ADT for mHSPC, 85 (91%) had subsequent treatment for mCRPC. Median time to mCRPC (biochemical, clinical or radiographic) had been 14.8 months (95% confidence interval [CI], 11.9–16.5). 1L treatment was enzalutamide 47 patients (55%), abiraterone 23 (27%), cabazitaxel 7 (8%), docetaxel 4 (5%) and other therapies 4 (5%). Median 1L TTF was 6.3 months (95% CI, 4.9–7.6), PSA > 50% reduction was achieved in 32 of 89 patients (36%), median time from 1L to second‐line treatment was 7.3 months (1.3–27.4), which did not differ significantly between treatment groups. Conclusions Abiraterone, enzalutamide, cabazitaxel and docetaxel all demonstrate activity following progression on D‐ADT. No difference in efficacy was detected between treatment options for mCRPC. Prospective trials investigating the optimal treatment sequence for prostate cancer following progression on D‐ADT needed.

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Platinum-based therapy in men with metastatic castration resistant prostate (mCRPC) with or without DNA repair defects: A multicentre retrospective analysis

Cited by 4 publications

References 0 publications

Beyond cabazitaxel: Late line treatments in metastatic castration resistant prostate cancer: A retrospective multicentre analysis

Beyond cabazitaxel: Late line treatments in metastatic castration resistant prostate cancer: A retrospective multicentre analysis

Decreased ATM Protein Expression Is Substantiated with PTEN Loss in Defining Aggressive Phenotype of Prostate Cancer Associated with Lethal Disease

Treatment outcomes for patients with metastatic castrate‐resistant prostate cancer following docetaxel for hormone‐sensitive disease

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