Clinical significance of AR mRNA quantification from circulating tumor cells (CTCs) in men with metastatic castration-resistant prostate cancer (mCRPC) treated with abiraterone (Abi) or enzalutamide (Enza).

2017 ◽  
Vol 35 (6_suppl) ◽  
pp. 132-132 ◽  
Author(s):  
John Silberstein ◽  
Brandon Luber ◽  
Hao Wang ◽  
Changxue Lu ◽  
Yan Chen ◽  
...  
Keyword(s):  
Cox Regression ◽  
Prognostic Significance ◽  
Progression Free Survival ◽  
Continuous Variable ◽  
Castration Resistant Prostate Cancer ◽  
Free Survival ◽  
Mrna Quantification ◽  
Castration Resistant ◽  
Kaplan Meier ◽  
Psa Progression

132 Background: AR-targeting agents remain the backbone of mCRPC therapy. We previously reported an association between AR-V7 mRNA detection in CTCs and resistance to Abi/Enza (NEJM 2014). Here, we report the prognostic significance of full-length androgen receptor (AR-FL) mRNA quantification from CTCs in pts starting Abi or Enza. Methods: We prospectively enrolled mCRPC pts starting Abi or Enza, and examined the prognostic value of AR-FL detection using a CTC-based mRNA assay (modified AdnaTest, Qiagen). We examined PSA50 responses, PSA progression free survival (PSA-PFS), clinical/radiologic PFS (PFS), and overall survival (OS). We constructed multivariable (MVA) Cox regression models adjusting for AR-V7 status, PSA level, Gleason sum, number of prior therapies, prior Abi/Enza use, prior taxane use, presence of visceral disease, and ECOG score. Results: We enrolled 202 pts (median f/u 12.9 mo). AR-FL status was negative in 97/202 pts (48%), < median in 52/202 (26%) and > median in 53/202 (26%). Higher AR-FL levels correlated with positive AR-V7 detection (35.5 copies [range: 2.5–1209] in AR-V7+ vs 1.4 copies [range: 0–172.5] in AR-V7–, P< .001), as well as lower PSA50 responses (55.4 copies in nonresponders vs 6.7 copies in responders, P< .001). In Kaplan-Meier analysis, PSA-PFS, PFS and OS differed significantly between AR-FL negative, AR-FL < median, and AR-FL > median (Table). In MVA models, AR-FL level (as a continuous variable) was prognostic for PSA-PFS (HR 1.06, 95%CI 1.00–1.12, P= .04) and trended with prognosis for PFS (HR 1.04, 95%CI 0.99–1.11, P= .13) and OS (HR 1.07, 95%CI 1.00–1.15, P= .06). AR-V7 status was also independently prognostic for all outcomes in MVA analyses. Conclusions: This study demonstrates CTC-derived AR-FL copy number is prognostic for clinical outcomes in Abi/Enza-treated mCRPC pts. In addition to AR-V7 status, AR-FL quantification could serve as another molecular biomarker of Abi/Enza sensitivity after analytical validation/standardization. [Table: see text]

The value of AKR1C3 in predicting the therapeutic efficacy of abiraterone for patients with metastatic castration-resistant prostate cancer.

2019 ◽  
Vol 37 (7_suppl) ◽  
pp. 313-313
Author(s):  
Jinge Zhao
Keyword(s):  
Prostate Cancer ◽  
Cox Regression ◽  
Prognostic Significance ◽  
Progression Free Survival ◽  
Castration Resistant Prostate Cancer ◽  
Free Survival ◽  
Androgen Synthesis ◽  
Castration Resistant ◽  
Psa Progression ◽  
The Difference

313 Background: AKR1C3 is a multifunctional enzyme playing a significant role in androgen synthesis and metabolism. Previous studies have proved that the activation of AKR1C3 was associated with resistance to abiraterone through increasing the intracrine androgen synthesis. However, clinical validation is still lacking as to the prognostic value of AKR1C3 in metastatic castration-resistant prostate cancer (mCRPC) patients treated with abiraterone. Methods: Data of 117 patients with mCRPC between 2016-2018 in our center were retrospectively analyzed. AKR1C3 was detected by the immunohistochemical staining from the 12-core prostate biopsy. Kaplan-Meier curves and COX regression were used to analyze the association between AKR1C3 and the treatment outcomes of abiraterone. The endpoints of this study were PSA progression-free survival (PSA-PFS) and radiograph progression-free survival (rPFS). Results: In total, AKR1V3 was detected in 40/117 (34.2%) cases. The positive AKR1C3 was significantly associated with shorter PSA-PFS for mCRPC patients treated with abiraterone (median PSA-PFS: 6.2 Mo vs. 11.1 Mo, p < 0.001). Those with positive AKR1C3 were also accompanied with obviously poorer rPFS compared to those with negative AKR1C3 staining, despite that the difference was not statistically significant (median rPFS: 11.1 Mo vs. 21.8 Mo, p = 0.250). Multivariate COX regression indicated that, AKR1C3 was an independent prognosticator of rapid PSA progression for the abiraterone treatment (HR,95%CI: 2.612, 1.54-4.44, p < 0.001). Conclusions: This is the first study verifying the adverse prognostic significance of AKR1C3 for mCRPC patients receiving abiraterone treatment. Our results suggested that, AKR1C3 was closely related to early treatment failure of abiraterone, and thus, was worthwhile to be routinely described in pathological report.

scholarly journals Response and Toxicity to the Second Course of 3 Cycles of 177Lu-PSMA Therapy Every 4 Weeks in Patients with Metastatic Castration-Resistant Prostate Cancer

Cancers ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 2489
Author(s):  
Sazan Rasul ◽  
Tim Wollenweber ◽  
Lucia Zisser ◽  
Elisabeth Kretschmer-Chott ◽  
Bernhard Grubmüller ◽  
...  
Keyword(s):  
Response Rate ◽  
Cox Regression ◽  
Progression Free Survival ◽  
Castration Resistant Prostate Cancer ◽  
Radioligand Therapy ◽  
Free Survival ◽  
Castration Resistant ◽  
Kaplan Meier ◽  
Node Metastases ◽  
Grade 3

Background: We investigated the response rate and degree of toxicity of a second course of three cycles of [177Lu]Lu-PSMA radioligand therapy (PSMA-RLT) every 4 weeks in mCRPC patients. Methods: Forty-three men (71.5 ± 6.6 years, median PSA 40.8 (0.87–1358 µg/L)) were studied. The response was based on the PSA level 4 weeks after the third cycle. The laboratory parameters before and one month after the last cycle were compared. Kaplan–Meier methods were used to estimate the progression-free survival (PFS) and overall survival (OS), and the Cox regression model was performed to find predictors of survival. Results: Twenty-six patients (60.5%) exhibited a PSA reduction (median PSA declined from 40.8 to 20.2, range 0.6–1926 µg/L, p = 0.002); 18 (42%) and 8 (19%) patients showed a PSA decline of ≥50% and ≥80%, respectively. The median OS and PFS were 136 and 31 weeks, respectively. The patients with only lymph node metastases survived longer (p = 0.02), whereas the patients with bone metastases had a shorter survival (p = 0.03). In the multivariate analysis, only the levels of PSA prior to the therapy remained significant for OS (p < 0.05, hazard ratio 2.43, 95% CI 1.01–5.87). The levels of hemoglobin (11.5 ± 1.7 g/dL vs. 11 ± 1.6 g/dL, p = 0.006) and platelets (208 ± 63 g/L vs. 185 ± 63 g/L, p = 0.002) significantly decreased one month after cycle three, though only two grade 3 anemia and one grade 3 thrombocytopenia were recorded. Conclusion: A further intensive PSMA-RLT course is well tolerated in mCRPC patients and associated with promising response rates and OS.

The effect of AKR1C3 on the switch from prednisone to dexamethasone in metastatic castration-resistant prostate cancer patients receiving abiraterone.

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 133-133
Author(s):  
Yuchao Ni ◽  
Jinge Zhao ◽  
Junru Chen ◽  
Guangxi Sun ◽  
Sha Zhu ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Progression Free Survival ◽  
Castration Resistant Prostate Cancer ◽  
First Line ◽  
Free Survival ◽  
Castration Resistant ◽  
Kaplan Meier ◽  
Psa Progression ◽  
Biochemical Progression ◽  
First Line Treatment

133 Background: Abiraterone is the first-line treatment for men with metastatic castration-resistant prostate cancer (mCRPC) and is recommended to be used with prednisone. Previous studies had demonstrated that the switch from prednisone to dexamethasone in some mCRPC patients can reverse abiraterone-resistance. However, it remains uncertain which group of patients will benefit from such switching. AKR1C3 is a critical enzyme contributing to the drug-resistance of abiraterone. Here, we aim to explore the significance of AKR1C3 in predicting the therapeutic efficacy of the corticosteroid switching in mCRPC patients receiving abiraterone. Methods: In total, 43 PCa patients treated with abiraterone after mCRPC between 2016 and 2018 in our institution were included. After biochemical progression in abiraterone plus prednisone, all cases received a corticosteroid switch to abiraterone plus dexamethasone. The expression of AKR1C3 was detected by immunohistochemical staining from re-biopsy (re‐Bx) of primary prostate lesions at the time of mCRPC. Kaplan‐Meier curves were used to analyze the association between AKR1C3 and treatment outcomes. Results: Totally, AKR1C3 was positive in 19 of 43 (44.19%) cases. In the corticosteroid switch treatment, 30% PSA decline was confirmed in 18/43 (41.86%) patients, while the median PSA progression‐free survival (PSA-PFS) and overall survival (OS) was 4.93 Mo and 31.57 Mo, respectively in the whole cohort. AKR1C3 expression was associated with statistically shorter median PSA-PFS (4.50 Mo vs 7.73 Mo; p =0.010) and numerically lower median OS (25.43 Mo vs 39.37 Mo, p =0.274). While the 30% PSA decline rate was numerically comparable between those with and without AKR1C3 expression (31.6% vs 50.0%, p =0.224). Conclusions: This study showed AKR1C3 detection in tissues from prostate re‐Bx at mCRPC was associated with poor PSA-PFS in the corticosteroid switch from abiraterone plus prednisone to abiraterone plus dexamethasone. These results would be helpful in making optimal personalized treatment decisions for patients with mCRPC, facilitating physicians predicting the effectiveness of corticosteroid switch treatment.

Biomarkers for early prognostication of outcome in patients with bone-metastatic castration-resistant prostate cancer treated with enzalutamide.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e16507-e16507
Author(s):  
Katrin Schlack ◽  
Martin Boegemann ◽  
Laura-Maria Krabbe ◽  
Karoline Kannen ◽  
Axel Semjonow ◽  
...  
Keyword(s):  
Cox Regression ◽  
Prospective Trial ◽  
Specific Antigen ◽  
Progression Free Survival ◽  
Castration Resistant Prostate Cancer ◽  
Early Therapy ◽  
Free Survival ◽  
Difficult Decision ◽  
Castration Resistant ◽  
Kaplan Meier

e16507 Background: Enzalutamide (Enza) prolongs survival in men with mCRPC in pre- and post chemotherapy setting. Commonly used prostate-specific antigen (PSA) may lead to non-straightforward prognosis. This is especially true for bone mCRPC (bmCRPC) in which initial bone-flare may add to difficult decision making. During other therapies, bouncing of alkaline phosphatase (ALP-Bounce) was shown as a promising surrogate for survival outcome. The purpose of this study was to evaluate the prognostic ability of ALP-Bounce compared to standard PSA and lactate dehydrogenase (LDH) after initiation of Enza. Methods: Patients with bmCRPC were included and analyzed. PSA, LDH and ALP were monitored at 2, 4, 8 and 12 weeks under very early Enza treatment. ALP-Bounce vs. no Bounce was analyzed using Kaplan-Meier estimates and uni- and multivariate (UV/MV) cox-regression models. ALP-Bounce was defined as an increase of ALP after initiation of Enza with a subsequent, significant decline below baseline during the first 8 weeks of therapy. Results: Eighty-nine men were evaluable for analysis. The median overall survival (OS) of men with ALP-Bounce was 19 months (95% confidence interval: 7.9-30.1) compared to 12 months (7.7-16.3) for no Bounce. Analysis of progression-free survival (PFS) showed similar results with 8 (0-16.3) vs. 3 months (1.9-4.1). In UV no ALP-Bounce (Hazard Ratio (HR): 1.9 (1.1-3.3); p = 0.02), no PSA-decline ≥50% (HR: 2.3 (1.5-3.7); p < 0.01) and no LDH-Normalization (HR: 2.5 (1.6-4.1); p < 0.01) were significantly associated with worse PFS. In MV only no ALP-Bounce showed a trend towards worse PFS (HR: 2.1 (0.9-4.5); p = 0.09). In UV no LDH-normalization was a significant prognosticator of poor OS (HR: 2.6 (1.6-4.2); p < 0.01) while ALP-Bounce and PSA decline ≥50% were non-prognostic. In MV no LDH-normalization remained an independent prognosticator of poor OS (HR: 2.0 (1.1.-3.5); p = 0.02). Conclusions: ALP-Bounce and LDH-Normalization may add to identification of bmCRPC-patients with favorable prognosis during early therapy with Enza. The early occurence of ALP-Bounce might be beneficial. These results have to be validated in a prospective trial.

Results of subset analyses on overall survival (OS) from study CA184-043: Ipilimumab (Ipi) versus placebo (Pbo) in post-docetaxel metastatic castration-resistant prostate cancer (mCRPC).

2014 ◽  
Vol 32 (4_suppl) ◽  
pp. 2-2 ◽  
Author(s):  
Charles G. Drake ◽  
Eugene D. Kwon ◽  
Karim Fizazi ◽  
Alberto Bossi ◽  
Alfons JM van den Eertwegh ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Statistical Significance ◽  
Progression Free Survival ◽  
Castration Resistant Prostate Cancer ◽  
Free Survival ◽  
Prognostic Features ◽  
Castration Resistant ◽  
Kaplan Meier ◽  
To Receive ◽  
Clinical Trial Information

2 Background: The CA184-043 phase 3 study did not reach statistical significance for its primary endpoint of OS (HR=0.85, p=0.053). However, antitumor activity was observed in other efficacy endpoints, including progression-free survival. Prespecified subset analyses were performed to understand if any prognostic features may identify mCRPC patients (pts) more likely to benefit from Ipi treatment. Methods: 799 pts were randomized to receive a single dose of radiotherapy (RT) followed by either Ipi (N=399) or Pbo (N=400). Prespecified subset analyses based on Kaplan-Meier/Cox methodology were performed using known prognostic factors for OS in mCRPC. Results: Prespecified subset analyses suggested that Ipi may be more active in pts with favorable prognostic factors, including no visceral disease, alkaline phosphatase <1.5 ULN, and hemoglobin ≥11 g/dL (Table). The safety profile in this study was consistent with previous reports of Ipi. Conclusions: Based on these subset analyses, Ipi added to RT appears to have greater activity than RT alone in pts with a favorable prognostic profile. These results support continued investigation of Ipi in the ongoing CA184-095 study in chemotherapy-naive mCRPC pts. Clinical trial information: NCT00861614. [Table: see text]

Blood platelet volume to predict treatment-specific outcomes of metastatic castration-resistant prostate cancer.

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 242-242
Author(s):  
Wataru Fukuokaya ◽  
Takahiro Kimura ◽  
Fumihiko Urabe ◽  
Shoji Kimura ◽  
Kojiro Tashiro ◽  
...  
Keyword(s):  
Radiographic Progression ◽  
Cox Regression ◽  
Progression Free Survival ◽  
Line Treatment ◽  
Castration Resistant Prostate Cancer ◽  
First Line ◽  
Castration Resistant ◽  
Psa Progression ◽  
Pre Treatment ◽  
First Line Treatment

242 Background: In the present guidelines for the management of metastatic castration-resistant prostate cancer (CRPC), it is unclear who benefits from androgen receptor axis-targeted agents (ARATs) or docetaxel as a first-line treatment. Methods: We conducted a single-institutional retrospective study to explore treatment-specific biomarkers for treatment response of metastatic CRPC. A cohort of 211 patients with metastatic CRPC treated with either ARAT (abiraterone acetate or enzalutamide) or docetaxel as a first-line treatment was evaluated. In addition to well-established biomarkers such as hemoglobin, neutrophil-to-lymphocyte ratio, alkaline phosphatase, and lactate dehydrogenase, we also assessed red cell distribution width, platelet count, and mean platelet volume (MPV). Laboratory measures were assessed within 1 month before starting treatment. Prostate-specific antigen progression-free survival (PSA-PFS) and radiographic progression-free survival (RPFS) were evaluated. Multivariable Cox regression models were used to assess the association between biomarkers and the risk of events. We also studied the statistical interaction between biomarkers and clinical outcomes. Results: Of all blood-based biomarkers, multivariable Cox regression models identified pre-treatment MPV (≤9.0 fL) as an independent prognostic factor of both PSA progression (hazard ratio [HR]: 2.62, 95% confidence interval [CI]: 1.25-5.48, P = 0.011) and radiographic progression (HR: 4.46, 95% CI: 1.79-11.1, P = 0.001). In addition, these models showed a lower risk of PSA progression (HR: 0.38, 95% CI: 0.15-0.96, P = 0.041) and radiographic progression (HR: 0.16, 95% CI: 0.05-0.50, P = 0.002) with docetaxel compared with ARAT when pre-treatment MPV was small. Conclusions: The present study identified MPV as a significant treatment-specific prognostic factor of PSA progression and radiographic progression in patients with metastatic CRPC treated with a first-line treatment. Furthermore, our results suggested that small MPV was associated with superior survival benefit on docetaxel over ARAT.

Clinical factors associated with AR-V7 detection in ARMOR3-SV, a randomized trial of galeterone (Gal) vs enzalutamide (Enz) in men with AR-V7+ metastatic castration-resistant prostate cancer (mCRPC).

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 5005-5005 ◽  
Author(s):  
Mary-Ellen Taplin ◽  
Emmanuel S. Antonarakis ◽  
Karen J. Ferrante ◽  
Kerry Horgan ◽  
Brent A. Blumenstein ◽  
...  
Keyword(s):  
Median Time ◽  
Primary Endpoint ◽  
Progression Free Survival ◽  
Castration Resistant Prostate Cancer ◽  
Open Label ◽  
Free Survival ◽  
Castration Resistant ◽  
Treatment Naïve ◽  
Psa Progression ◽  
Study Designs

5005 Background: Presence of the AR-V7 splice variant may predict resistance to Enz and abiraterone in men with mCRPC. Gal is an oral agent that disrupts AR signaling via AR degradation, CYP17 lyase inhibition, and AR antagonism. ARMOR3-SV was designed to test the hypothesis that in mCRPC patients with AR-V7+ CTCs, Gal could improve radiographic progression-free survival (rPFS) versus Enz. Methods: In this randomized, open-label, multicenter phase 3 study (NCT02438007), men with treatment-naïve mCRPC were screened for CTC-specific AR-V7 (Qiagen), and AR-V7+ men were randomized 1:1 to Gal or Enz. rPFS (by independent blinded central review) was the primary endpoint. Planned sample size was 148, with 120 rPFS events to achieve 90% power to detect a hazard ratio of ≤0.55. Results: 953 patients were screened globally for AR-V7 from Sept 2015 through study closure; 73 men (8%; 95% CI 6-10%) were AR-V7+, 250 (26%) AR-V7–, and 630 (66%) had no CTCs/AR present (unevaluable). AR-V7 detection was associated with higher PSA levels ( > vs < median; P < 0.01), more bone metastases ( > 20 vs 11-20 vs 6-10 vs 0-5; P < 0.01), presence of M1 disease at diagnosis (dx) (yes vs no; P = 0.04), shorter time from dx to screening ( < vs > median; P < 0.01), higher ECOG (≥1 vs 0; P = 0.02), prior antiandrogen use (yes vs no; P < 0.01) and prior docetaxel use (yes vs no; P < 0.01). Among the AR-V7+ men, 38 were randomized (19 Gal, 19 Enz), 31 screen failed, and 4 were discontinued from screening at study halt. Baseline characteristics were balanced. On the recommendation of the DSMB, the study was closed early as it was unlikely to meet its primary endpoint. At the time of the study closure, in the Gal and Enz arms respectively, median time on therapy was 2.0 vs 2.8 mo, median time to PSA progression (PCWG1) was 3.9 vs 3.8 mo, PSA50 response rates in evaluable patients were 2/16 (13%) and 8/19 (42%), and there were no new safety signals. Conclusions: In treatment-naïve mCRPC patients, AR-V7 detection is more common in men with higher disease burden and portends a poor prognosis. Novel study designs and alternative treatment approaches are urgently needed for AR-V7+ mCRPC patients. Clinical trial information: NCT02438007.

Redefining postprostatectomy biochemical progression: The significance of a PSA cutoff below 0.2 ng/ml—Results from two retrospective series with and without salvage radiotherapy.

2015 ◽  
Vol 33 (7_suppl) ◽  
pp. 153-153
Author(s):  
Lars Budäus ◽  
Jonas Schiffmann ◽  
Pierre Tennstedt ◽  
Dirk Bottke ◽  
Hans Heinzer ◽  
...  
Keyword(s):  
Overall Survival ◽  
Cox Regression ◽  
Progression Free Survival ◽  
Salvage Radiotherapy ◽  
Clinical Progression ◽  
Free Survival ◽  
Kaplan Meier ◽  
Psa Progression ◽  
Biochemical Progression

153 Background: Biochemical recurrence (BCR) after radical prostatectomy (RP) is usually defined at a PSA >0.2 ng/ml. BCR may precede clinical progression by years. Though salvage radiotherapy (SRT) is recommend to be initiated at PSA <0.5 ng/ml, its efficiency at PSA <0.2 ng/ml is not well documented. Methods: We relied on two independent post-RP cohorts. Cohort 1 (n=311, Hamburg) comprised men whose post-RP PSA levels had risen to 0.1-0.2 ng/ml. Further biochemical and clinical progression were recorded during follow-up. Cohort 2 (n=198, Berlin) were patients with BCR who received SRT (66/72 Gy) at a PSA <0.5 ng/ml. The median follow-up was 6.9 years. Post-SRT progression and overall survival were addressed by Kaplan-Meier analysis and Cox regression modelling. Results: In cohort 1, 299 (96%) men experienced further PSA progression (>0.2 ng/ml) within a median time of 7 months. Subsequent PSA rise to >0.3, >0.4, and >0.6 ng/ml was recorded in 174 (58%), 123 (41%), and 24 (8%) men, respectively. Twenty-four (8%) men developed metastases. In cohort 2, 112 men received SRT at PSA between 0.03 and 0.2 ng/ml, and 86 at 0.2-0.499 ng/ml. The latter group, had a poorer 10-years BCR-free Kaplan-Meier rate, 43% vs. 66% (p=0.051). Together with pT<3, Gleason Score <7, and post-RP PSA <0.03 ng/ml, SRT at PSA <0.2 ng/ml was an independent favorable predictor of freedom from BCR (OR=0.60, p<0.05). Ultimately, 14 patients died. However, overall survival did not significantly correlate with the pre-SRT PSA. Conclusions: The vast majority of patients with a PSA >0.1 ng/ml after RP will subsequently progress to PSA >0.2 ng/ml. Improved progression free survival can be achieved, if SRT is administered at a PSA <0.2 ng/ml. Therefore the contemporary PSA threshold for defining BCR after RP needs to be reconsidered and early sRT should be contemplated on a individual basis for optimizing oncological outcomes.

Surrogacy analysis of prostate-specific antigen (PSA) decline for improved overall survival (OS) with enzalutamide (ENZ) in AFFIRM.

2016 ◽  
Vol 34 (2_suppl) ◽  
pp. 266-266
Author(s):  
Andrew J. Armstrong ◽  
Fred Saad ◽  
Neal D. Shore ◽  
Karim Fizazi ◽  
De Phung ◽  
...  
Keyword(s):  
Treatment Effect ◽  
Prognostic Significance ◽  
Specific Antigen ◽  
Progression Free Survival ◽  
Pain Response ◽  
Castration Resistant Prostate Cancer ◽  
Free Survival ◽  
Castration Resistant ◽  
Post Hoc

266 Background: ENZ significantly increased OS for men with metastatic castration-resistant prostate cancer (mCRPC) vs. placebo and significantly decreased PSA levels. However, the prognostic significance and role of PSA falls as a surrogate for OS are not established. Methods: Men in the AFFIRM trial were grouped by maximal unconfirmed PSA decline during the 1st 90 days of treatment in a post-hoc analysis. Each PSA decline criterion was assessed for surrogacy for OS by the proportion of treatment effect (PTE)-explained and Prentice criteria. We also assessed the association of PSA decline with OS, progression-free survival (PFS), and pain response. Results: ENZ improved OS (hazard ratio 0.63, p < 0.001) and was associated with higher rates of PSA declines when compared to placebo (odds ratio > 19.0, p < 0.001). Greater declines in PSA were associated with longer OS, PSA PFS, radiographic PFS, and higher pain response when compared with no PSA decline or PSA increase (table). All decline measures from baseline were highly prognostic for OS and several ( > 0%, ≥ 30%, ≥ 50% declines) explained a proportion of the treatment effect (PTE 1.07–1.29, 95% CI lower bounds > 0.63), in which treatment was no longer significant after adjustment for the decline measures (p > 0.20). Full surrogacy was not demonstrated. Conclusions: In AFFIRM, > 0, ≥30%, and ≥50% PSA declines within 90 days of treatment fulfilled Prentice surrogacy criteria 1–3. Prentice 4, equivalency of survival adjusting for PSA decline outcomes, could not be demonstrated. PSA declines are associated with longer PFS and improved pain response. External prospective validation is needed. Clinical trial information: NCT00974311. [Table: see text]

scholarly journals Prognostic value of the albumin–globulin ratio and albumin–globulin score in patients with multiple myeloma

2021 ◽  
Vol 49 (3) ◽  
pp. 030006052199773
Author(s):  
Ying Cai ◽  
Yu Zhao ◽  
Qiuxin Dai ◽  
Maozhong Xu ◽  
Xin Xu ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Prognostic Value ◽  
Cox Regression ◽  
Characteristic Curve ◽  
Prognostic Significance ◽  
Progression Free Survival ◽  
Free Survival ◽  
Cox Regression Analysis ◽  
Kaplan Meier

Objective The albumin–globulin ratio (AGR) has been identified as a promising prognostic predictor of mortality in patients with hematological malignancies. This study investigated the prognostic significance of AGR in patients with multiple myeloma. Methods Two hundred patients diagnosed with multiple myeloma from January 2010 to October 2018 were retrospectively analyzed and followed up until December 2019. Kaplan–Meier curves and multivariate Cox regression analysis were applied to detect the prognostic value of AGR. Results The median follow-up period was 36 months. The optimal cutoff of AGR was 1.16 according to receiver operating characteristic curve analysis. High AGR was significantly correlated with better overall survival (OS) and progression-free survival (PFS). Multivariate analysis revealed that low AGR was an independent prognostic factor for worse OS (hazard ratio [HR] = 1.82, 95% confidence interval [CI] = 1.15–2.94) and PFS (HR = 1.53, 95% CI = 1.09–2.17). Conclusions AGR may represent a potential prognostic biomarker in patients with multiple myeloma. Mini Abstract: We demonstrated that high AGR was associated with a favorable overall survival and progression-free survival in patients with multiple myeloma.

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