scholarly journals Early PSA Change after [177Lu]PSMA-617 Radioligand Therapy as a Predicator of Biochemical Response and Overall Survival

Cancers ◽  
2021 ◽  
Vol 14 (1) ◽  
pp. 149
Author(s):  
Felix Kind ◽  
Thomas F. Fassbender ◽  
Geoffroy Andrieux ◽  
Melanie Boerries ◽  
Philipp T. Meyer ◽  
...  

Purpose: Radioligand therapy with [177Lu]PSMA-617 (PSMA-RLT) is a promising therapeutic option for metastatic castration-resistant prostate cancer (mCPRP). This study assessed the prognostic value of early PSA measurements during PSMA-RLT. Methods: 27 patients with mCRPC scheduled for PSMA-RLT were prospectively enrolled for a serial short-interval PSA-assessment. Change in PSA (∆%PSA) during two treatment cycles was correlated with biochemical response (BR) and change in tumor volume on PET (TV) after 16 weeks (w16), as well as overall survival (OS). PCWG3 criteria and the recently recommended threshold of ∆%PSA ≤ −30% were assessed for their predictive value. Results: ∆%PSA first correlated with BR, TV and OS after 4 weeks (c1w4). At c1w4, ∆%PSA ≤ −30% was associated with the biochemical response at w16 (p = 0.003) and a longer median OS (p = 0.025), whereas the PCWG3-derived threshold of ∆%PSA ≤ −50% showed no such correlation. In contrast, ∆%PSA ≥ 25% at c1w4 was associated with biochemical progression at w16 (p = 0.003) and a shorter median OS (p < 0.001). Conclusion: PSA changes as early as four weeks after PSMA-RLT allow a significant prediction of later biochemical and PET-based imaging response, as well as OS. At this early time point, a more lenient threshold for a PSA decrease of at least 30% appears better-suited for the prediction of a positive biochemical response and longer OS. In contrast, the PCWG3-derived threshold for PSA increase (+25%) reliably anticipates biochemical progression and shorter OS.

Cancers ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 2938
Author(s):  
Liam Widjaja ◽  
Rudolf A. Werner ◽  
Tobias L. Ross ◽  
Frank M. Bengel ◽  
Thorsten Derlin

177Lu-Prostate-specific membrane antigen (PSMA)-radioligand therapy (RLT) is a promising treatment option in patients with metastatic castration-resistant prostate cancer (mCRPC). We aimed to determine the predictive value of pretherapeutic PSMA-ligand positron emission tomography (PET) and established clinical parameters for early biochemical response after two cycles of RLT. In total, 71 mCRPC patients who had undergone PET/computed tomography (CT) with 68Ga-PSMA-11 prior to two cycles of 177Lu-PSMA-617 RLT were included. Malignant lesions on pretherapeutic PET/CTs were manually segmented and average maximum PSMA expression (maximum standardized uptake values, SUVmax), whole-body PSMA-tumor volume (TV), and whole-body total lesion (TL)-PSMA were calculated. We then tested the predictive performance of these parameters for early biochemical response (defined as prostate-sepcific antigen (PSA) decrease of ≥50% according to PCWG2) after two cycles of RLT, relative to established clinical parameters. Early PSA response was observed in 34/71 patients. PSA change after two cycles of RLT correlated with pretherapeutic SUVmax (r = −0.49; p < 0.001), but not with PSMA-TV (r = 0.02; p = 0.89) or TL-PSMA (r = −0.15; p = 0.22). A cut-off of 19.8 for SUVmax and 75.5 years for age was defined by receiver operating characteristics and revealed a significant outcome difference for early biochemical response between patients with adversely low vs. high PSMA expression and low vs. high age (p < 0.001). Multivariate analysis identified SUVmax (HR, 7.94, p = 0.001) and age (HR, 8.05, p = 0.002) as independent predictors for PSA response early in the treatment course. Thus, high age and high PSMA expression in patients scheduled for RLT identify patients with early biochemical response. This study provides a rationale for further prospective studies exploring PET-guided treatment intensification in selected patients.


Author(s):  
Florian Rosar ◽  
Felix Wenner ◽  
Fadi Khreish ◽  
Sebastian Dewes ◽  
Gudrun Wagenpfeil ◽  
...  

Abstract Purpose In patients with metastatic castration-resistant prostate cancer (mCRPC) treated with prostate-specific membrane antigen-targeted radioligand therapy (PSMA-RLT), the predictive value of PSMA PET/CT-derived response is still under investigation. Early molecular imaging response based on total viable tumor burden and its association with overall survival (OS) was explored in this study. Methods Sixty-six mCRPC patients who received [177Lu]Lu-PSMA-617 RLT within a prospective patient registry (REALITY Study, NCT04833517) were analyzed. Patients received a [68Ga]Ga-PSMA-11 PET/CT scan before the first and after the second cycle of PSMA-RLT. Total lesion PSMA (TLP) was determined by semiautomatic whole-body tumor segmentation. Molecular imaging response was assessed by change in TLP and modified PERCIST criteria. Biochemical response was assessed using standard serum PSA and PCWG3 criteria. Both response assessment methods and additional baseline parameters were analyzed regarding their association with OS by univariate and multivariable analysis. Results By molecular imaging, 40/66 (60.6%) patients showed partial remission (PR), 19/66 (28.7%) stable disease (SD), and 7/66 (10.6%) progressive disease (PD). Biochemical response assessment revealed PR in 34/66 (51.5%) patients, SD in 20/66 (30.3%), and PD in 12/66 (18.2%). Response assessments were concordant in 49/66 (74.3%) cases. On univariate analysis, both molecular and biochemical response (p = 0.001 and 0.008, respectively) as well as two baseline characteristics (ALP and ECOG) were each significantly associated with OS. The median OS of patients showing molecular PR was 24.6 versus 10.7 months in the remaining patients (with SD or PD). On multivariable analysis molecular imaging response remained an independent predictor of OS (p = 0.002), eliminating biochemical response as insignificant (p = 0.515). Conclusion The new whole-body molecular imaging–derived biomarker, early change of total lesion PSMA (TLP), independently predicts overall survival in [177Lu]Lu-PSMA-617 RLT in mCRPC, outperforming conventional PSA-based response assessment. TLP might be considered a more distinguished and advanced biomarker for monitoring PSMA-RLT over commonly used serum PSA.


2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 97-97
Author(s):  
Cedric Pobel ◽  
Edouard Auclin ◽  
Diego Teyssonneau ◽  
Brigitte Laguerre ◽  
Mathilde Cancel ◽  
...  

97 Background: Cabazitaxel rechallenge could be a more efficient therapy with an acceptable toxicity than docetaxel in the treatment of patients with a metastatic castration resistant prostate cancer (mCRPC). The aim of this study was to assess the feasibility and efficacy of cabazitaxel multiple rechallenge. Methods: This is a multicenter, retrospective cohort study including patients from 9 centers in France who received 3 lines or more of cabazitaxel from February 2012 to July 2020. Cabazitaxel schedule differed between patients: 25 mg/m2 q3w, 20 mg/m2 q3w, 16 mg/m2 q2w or 10 mg/m2 weekly. Efficacy was assessed by overall survival (OS) and progression-free survival (PFS) from each cabazitaxel line start. Only toxicities grade ≥ 3 were reported. Results: Twenty-two patients were included. The median follow-up from mCRPC was 94.7 months, median age at initial diagnosis was 59.5 years old, median ISUP score at diagnosis was 4 and median PSA at diagnosis was 55 ng/ml. Median number of cabazitaxel cycles was 7 at first-line, 6 at first rechallenge, and 5 for subsequent rechallenges. Median OS from mCRPC diagnosis was 105 months. Median PFS from cabazitaxel line start was 11.8 months at first use, 9.6 for first rechallenge and 5.6 in second rechallenge (table). Only one case of febrile neutropenia and 6 events of grade ≥ 3 toxicity were reported. Conclusions: Cabazitaxel multiple rechallenge could efficiently extend OS with manageable toxicities for patients. Even if anti-PARP therapy and immunotherapy are promising treatments, cabazitaxel rechallenge could be also a relevant therapeutic option for long responder patients. Specific biomarkers should be explored to predict the efficacy of cabazitaxel rechallenge. [Table: see text]


2019 ◽  
Vol 37 (7_suppl) ◽  
pp. 303-303
Author(s):  
Prantik Das ◽  
James Price ◽  
Michael Jones ◽  
Cristina Martin-Fernandez ◽  
Akram Ali ◽  
...  

303 Background: Abiraterone acetate (a prodrug of abiraterone, which is a selective inhibitor of androgen biosynthesis) combined with prednisone/prednisolone (AA+P) and enzalutamide (ENZ) (an androgen-receptor–signalling inhibitor) have proven survival benefit in men with metastatic castration resistant prostate cancer (mCRPC) in chemo naïve and prior chemo patients. There have been no studies directly comparing the effectiveness of ENZ to AA+P in mCRPC patients. Methods: A retrospective, survival analysis study of 143 real world mCRPC patients (90 in AA+P and 53 in ENZ group) was conducted. Patients who started their treatment between 1st February 2012 and 31st May 2016 were included. The primary endpoint was biochemical progression free survival (PFS). Secondary end points were radiographic progression free survival (rPFS) and overall survival (OS). Data was analysed using Cox proportional hazards models, adjusting for covariates: prior radical or palliative treatment; Gleason score; baseline PSA; age; and chemo naïve or not. Results: After median follow up of 15 months (IQR 7 to 23) 112 events of biochemical progression were observed (71 in AA+P and 41 in ENZ). 41%in AA+P group and 30% patients in ENZ group received prior chemo. The chance of biochemical progression was significantly lower among ENZ patients than AA+P patients, when adjusting for all covariates in the Cox PH model (Hazard Ratio 0.54, 95% CI 0.35 to 0.82, p=0.004. There was a trend implying the chance of rPFS could be higher among ENZ patients than AA+P patients (HR 1.24, 95% CI 0.76 to 2.02, p=0.4). OS is lower among ENZ patients than AA+P patients, when adjusting for all covariates in the Cox PH model (HR 0.91, 95% CI 0.59 to 1.41, p=0.7). 38% of ENZ patients reported fatigue compared to 16% of AA+P patients while hypertension was reported slightly more in AA+P patients than in ENZ patients. Conclusions: This study showed a statistically significant difference in biochemical progression-free survival, favouring ENZ, but no significant difference in radiographic progression-free survival or overall survival.


2021 ◽  
Vol 93 (4) ◽  
pp. 393-398
Author(s):  
Roberto Saldanha Jarimba ◽  
Miguel Nobre Eliseu ◽  
João Pedroso Lima ◽  
Vasco Quaresma ◽  
Pedro Moreira ◽  
...  

Introduction: Prostate cancer is the most common cancer in men, accounting for 15% of all diagnosed cancers and is the sixth leading cause of cancerrelated deaths amongst men worldwide. Abiraterone and enzalutamide were the first two novel hormonal agents approved for the treatment of metastatic prostate cancer but there is a lack of quality evidence regarding which is associated with better outcomes and who would benefit the most with one or another of these drugs. Objective: To evaluate the clinical outcomes of real-world patients submitted to treatment with novel hormonal agents, enzalutamide and abiraterone, for castration resistant metastatic prostate cancer in an academic center.Patients and methods: We retrospectively reviewed patients treated for castration-resistant prostate cancer with either abiraterone or enzulatamide between January 1, 2016 and December 31, 2019. The primary endpoints were biochemical response, biochemical progression, radiological progression, clinical deterioration (attributed to disease progression) and death. Results: Enzalutamide had a higher biochemical response rate than abiraterone in patients with mCRPC (77.1% vs 58.1%, p = 0.016). Achieving a biochemical response was associated with a lower risk of biochemical progression (OR: 0.248, p = 0.017) and death (OR: 0.302, p = 0.038). Conclusions: Enzalutamide conferred higher biochemical response rate than abiraterone in patients with mCRPC. Despite the trend to better performance of other endpoints in the enzalutamide group, it did not achieve statistical significance. Well-designed prospective studies are needed to elucidate the comparative efficacies of these agents.


Oncotarget ◽  
2017 ◽  
Vol 8 (61) ◽  
pp. 103108-103116 ◽  
Author(s):  
Hojjat Ahmadzadehfar ◽  
Stephan Schlolaut ◽  
Rolf Fimmers ◽  
Anna Yordanova ◽  
Stefan Hirzebruch ◽  
...  

2011 ◽  
Vol 29 (7_suppl) ◽  
pp. 165-165
Author(s):  
O. Caffo ◽  
S. Brugnara ◽  
A. Caldara ◽  
A. Ferro ◽  
M. Frisinghelli ◽  
...  

165 Background: Responder pts to first-line DOC, who have stopped the treatment in absence of progression, usually experience a disease progression within few months. In recent years, ReC with DOC has emerged as a therapeutic option for these pts, able to achieve again a response. The available data usually report on the clinical outcome of pts who have received one or two ReCs, but it is unclear whether more ReCs may be offered to these pts and if there is a maximum number of affordable ReCs. Methods: We retrospectively reviewed the clinical record of the pts with CRPC treated in our Department with DOC from March, 2002 to September, 2010. We selected pts who received multiple ReCs until the appearance of a true resistance to DOC: we consider as DOC-resistant pts showing a clinical and/or biochemical progression during DOC treatment. Results: We have identified a consecutive series of 26 pts, who have received a median number of 2 ReCs (range 2- 6). The median age was 68 yrs (range 58-82 yrs). The ReC consisted of DOC q 3 wks in 7 cases, DOC + estramustine q 3 wks in 38, weekly DOC + estramustine in 23. Multiple ReCs were well tolerated with no more than grade 1 hematological and non-hematological toxicities. To date, 11 pts are still DOC-sensitive (after 2-6 ReCs, median 2) and are receiving ReCs or are in the off-therapy period after ReCs. After a median follow-up of 30 months, 14 pts are dead and 12 alive. The median survival is 40 mos and the projected 3-years overall survival is 54%. Conclusions: In our experience multiple DOC ReCs may be administered in DOC-sensitive pts with CRPC. This may provide a long-term disease control with remarkable survival rate compared to those of DOC pivotal studies (19 mos) and a second line treatment may be retarded until the appearance of a true DOC-resistance. [Table: see text] No significant financial relationships to disclose.


2016 ◽  
Vol 41 (7) ◽  
pp. 522-528 ◽  
Author(s):  
Kambiz Rahbar ◽  
Axel Bode ◽  
Matthias Weckesser ◽  
Nemanja Avramovic ◽  
Michael Claesener ◽  
...  

2020 ◽  
Vol 21 (23) ◽  
pp. 9054
Author(s):  
Finn Edler von Eyben ◽  
Glenn Bauman ◽  
Rie von Eyben ◽  
Kambiz Rahbar ◽  
Cigdem Soydal ◽  
...  

The aim of the review was to evaluate patient and treatment characteristics for patients with metastatic castration-resistant prostate cancer (mCRPC) treated with PSMA radioligand therapy (PRLT) associated with above-average outcome. The systematic review and meta-analysis followed recommendations by the Preferred Reporting Items for Systematic reviews and Meta-Analysis (PRISMA). We searched for publications in PubMed, Embase, and ClinicalTrials.gov up to 31 September 2020. Thirty-six publications and four duplicates reported 2346 patients. Nearly two-thirds of the patients had bone metastases. Median overall survival (OS) was 16 months. Asymptomatic patients and patients with only lymph node metastases lived longer than symptomatic patients and patients with more extensive metastases. Patients treated with an intensified schedule of 177Lu PRLT lived longer than those treated with a conventional schedule. Half of the patients obtained a PSA decline ≥ 50% and these patients lived longer than those with less PSA decline. Approximately 10% of the patients developed hematologic toxicity with anemia grade 3 as the most severe adverse effect. Characteristics for patients, cancer, restaging, and PRLT predict above average overall survival following treatment with PRLT.


2017 ◽  
Vol 35 (6_suppl) ◽  
pp. 155-155 ◽  
Author(s):  
Kambiz Rahbar ◽  
Hojjat Ahmadzadehfar ◽  
Clemens Kratochwil ◽  
Richard P. Baum ◽  
Matthias Schmidt ◽  
...  

155 Background: Prostate specific membrane antigen (PSMA) is a promising target for imaging and therapy of prostate cancer. Small cohorts trials have shown promising results for response and tolerability of 177Lu-PSMA-617 radioligand therapy (RLT) in patients with metastatic castration-resistant disease. The aim of this multicenter study was to investigate safety and efficacy of this new therapy in a large, multicenter cohort. Methods: Data of 145 patients with metastatic castration resistant prostate cancer treated with at least a single dose of 177Lu-PSMA-617 at 12 therapy centers in Germany (median age 73 years, range 43-88) were collected. Up to 4 therapy cycles (range of administered activity 2 – 8 GBq) were given. Toxicity was categorized by the common toxicity criteria for adverse events based on serial blood tests and the physician’s report. Biochemical response was defined by a PSA decline ≥ 50% from baseline. Results: 248 therapy cycles were performed. Data for biochemical response were available in 99 patients and data for physician-reported and lab-based toxicity in 145 and 121 patients. The median follow-up was 16 weeks (range 2-30 weeks). Nineteen patients died during the observation period. Grade 3 to 4 hematotoxicity occurred in 18 patients: 10%, 4% and 3% of the patients experienced anemia, thrombocytopenia and leukopenia, respectively. Xerostomia occurred in 8%. Overall biochemical response rate was 45% following all therapy cycles. Elevated alkaline phosphatase and presence of visceral metastases were negatively correlated and the total number of therapy cycles correlated positively with biochemical response. 22 of 31 patients with no PSA decline > 50% after the first cycle did not respond to the second therapy cycle. Conclusions: Radioligand therapy with 177Lu-PSMA-617 shows promising response rates and a low toxicity in extensively pretreated patients with prostate cancer. Future prospective trials have to evaluate the effect of RLT on survival and potentially be considered in earlier stages of prostate cancer.


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