Association of androgen receptor (AR) gene status in plasma DNA with outcome on enzalutamide in chemotherapy-naive metastatic castration-resistant prostate cancer (mCRPC): Exploratory results from the PREMIERE trial—On behalf of SOGUG.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 5016-5016
Author(s):  
Enrique Grande ◽  
Albert Font Pous ◽  
Natalia Fernández Núñez ◽  
Aranzazu Gonzalez del Alba ◽  
Begoña Mellado ◽  
...  
Keyword(s):  
Cox Regression ◽  
Progression Free Survival ◽  
Digital Pcr ◽  
Castration Resistant Prostate Cancer ◽  
Plasma Dna ◽  
Free Survival ◽  
Exact Test ◽  
Road Map ◽  
Psa Response ◽  
Gene Status

5016 Background: Building on previous discoveries studying AR status in plasma (Carreira S, Sci Transl Med 2014, Romanel A, Sci Transl Med 2015) and following a road-map for biomarker development, we aimed to clinically qualify AR status in chemotherapy-naïve mCRPC using an optimized multiplex droplet digital PCR (ddPCR) assay (Condeduca et al.;ASCO2017;Abstract#). Methods: Between February and November 2015, 98 asymptomatic or oligo-symptomatic chemotherapy-naïve mCRPC patients were recruited in 16 Spanish hospitals. Tissue and blood samples were required at study entry. Although initially designed to study the predictive value of TMPRSS2-ETS, data emerging after the trial was initiated led the group to prioritize alternative predefined exploratory biomarkers, including plasma ARand CTC characterization (Grande E. ESMO 2016 & Font A. et al; ASCO2017; Abstract #). Outcome measures included PSA-progression-free survival (sPFS), radiographic progression-free survival (rPFS) and overall survival (OS). Cox regression was used for survival analyses and Fisher’s exact test for PSA response. Results: Ninety-four patients had plasma DNA available for analysis. At baseline, AR gain was present in 11 pts (12%) and CTCs in 35 (37%). AR gain in CTC-positive and negative patients was 20% and 7%, respectively. At first interim analysis and with a median follow-up of 10.6 months, detection of AR gain was associated with worse sPFS (median, 3.60 versus 15.5 m, HR, 4.33; 95% CI 1.94-9.68; P < 0.001), rPFS (median, 3.90 m versus not reached HR, 8.06; 95% CI, 3.26-19.93; P < 0.001) and OS (medians not reached, HR, 11.08; 95% CI, 2.16-56.95; P = 0.004). These results were independently associated in multivariate analysis including cfDNA and CTCs for all described endpoints. AR gain patients were less likely to have a ≥50% decline in PSA (OR, 4.93; 95% CI, 1.30-18.75; P = 0.025). Conclusions: Detection of AR gain in plasma using a robust multiplex ddPCR method predicts an adverse outcome in chemotherapy-naïve mCRPC. Further prospective randomized studies are warranted. Clinical trial information: NCT02288936.

Comparison of abiraterone acetate (Abi) versus ketoconazole (Keto) in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) refractory to docetaxel (D).

2013 ◽  
Vol 31 (6_suppl) ◽  
pp. 146-146
Author(s):  
Avivit Peer ◽  
Maya Ish-Shalom ◽  
Natalie Maimon ◽  
Maya Gottfried ◽  
Ben Boursi ◽  
...  
Keyword(s):  
Overall Survival ◽  
Cox Regression ◽  
Progression Free Survival ◽  
Risk Category ◽  
Appendicular Skeleton ◽  
Castration Resistant Prostate Cancer ◽  
Time To Progression ◽  
Disease Extent ◽  
Free Survival ◽  
Psa Response

146 Background: Abi is a standard treatment (tx) in pts with mCRPC refractory to deocetaxel. It is a potent and selective CYP 17 inhibitor that blocks the synthesis of androgens in the testis, adrenal glands, and prostate. However, in many countries where abi has not been approved yet, keto is used as an alternative CYP 17 inhibitor. Although preclinical data suggests that keto is a less specific and potent inhibitor of CYP 17, there are limited clinical data comparing both agents. We aimed to compare the clinical effectiveness of abi vs keto in pts with mCRPC refractory to D. Methods: Records from 156 mCRPC pts treated with keto 200 - 400 mg 3x day, in 4 centers across the US and Israel, were reviewed retrospectively. 26 pts treated post D were individually matched by clinicopathologic factors to pts treated with abi (selected from a multicenter Israeli database, n=120). We compared the PSA response (decrease ≥50% from baseline), biochemical and radiological progression free survival, and overall survival between the groups. Progression free survival and overall survival were determined by Cox regression. Results: The groups were matched by Gleason score, pre-tx disease extent (limited-axial skeleton and/or nodal vs extensive- appendicular skeleton and/or visceral), ECOG PS, pre-tx risk category (favorable, intermediate, poor; Keizman, Oncologist 2012). Furthermore, they were balanced regarding median age (71 abi vs 69 keto), time from primary tx to disease relapse, time to progression on prior GnRH-a and antiandrogen, PSA response and time to progression on prior D, pre-tx pain score/alkaline phosphatase/hemoglobin/ neutrophil to lymphocyte ratio/PSADT/PSA. In the groups of abi vs keto, PSA response was 46% vs 19% (OR 4.4, p=0.043), median biochemical PFS 7 vs 2 months (HR 0.65, p=0.02), median radiological PFS 6 vs 2.5 months (HR 0.63, p=0.016), median overall survival 17 vs 12 months (HR 0.53, p=0.79), and tx interruption d/t adverse events 12% vs 23% (0R 0.6, p=0.023). Conclusions: In mCRPC refractory to D, the outcome of pts treated with abiraterone was superior to ketoconazole.

Gene expression in circulating tumor cells (CTC) and plasma androgen receptor (AR) gene copy number (CN) for castration-resistant prostate cancer (CRPC) patients (pts) treated with cabazitaxel.

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 154-154
Author(s):  
Giorgia Gurioli ◽  
Vincenza Conteduca ◽  
Umberto Basso ◽  
Giuseppe Fornarini ◽  
Alessandra Mosca ◽  
...  
Keyword(s):  
Gene Copy Number ◽  
Predictive Biomarkers ◽  
Progression Free Survival ◽  
Digital Pcr ◽  
Gene Copy ◽  
Castration Resistant Prostate Cancer ◽  
Plasma Dna ◽  
Castration Resistant ◽  
Significant Difference ◽  
Psa Response

154 Background: Cabazitaxel demonstrated overall survival (OS) benefit for the treatment of CRPC progressing after docetaxel. CTC profiling could help to establish novel predictive biomarkers. In this prospective study (NCT03381326), we evaluated the prognostic role of CTC biomarkers expression and the association with plasma AR CN in pts treated with cabazitaxel. Methods: We enrolled pts receiving cabazitaxel from January 2015 to December 2018. Plasma DNA was isolated and digital PCR was performed to assess AR CN status. CTC enrichment was evaluated with AdnaTest EMT-2/StemCell kit. Expression analyses using real time PCR were performed for 17 genes and CTC positivity (CTC+) was defined as the expression of at least 1 of the following 7 relevant markers: AR-V7, AKT, AR, EPCAM, PSMA, PI3KCA, PSCA. Results: We enrolled 100 pts, 80 fully evaluable for this analysis. Median age was 72 years (range 49-82). All pts received prior docetaxel and 85% prior abiraterone and/or enzalutamide. Median OS and progression-free survival (PFS) were 16.4 months (mo) (95% CI 11.1-27.0) and 6.7 mo (95% CI 5.2-8.3), respectively. Fifty-eight (72.5%) showed CTC+ at baseline, whose 15 (26%) had >3 markers expressed in CTC. Significantly worse OS was observed in pts with >3 markers expressed in CTC compared to those with ≤3 markers and CTC negative pts [4.7 mo vs 15.2 vs 31.7 mo respectively, hazard ratio (HR) 6.05 (95% CI 2.07-17.73), p=0.004]. No significant difference was observed for PFS and PSA response. AR-V7 was expressed in 11 (19%) CTC+ pts, whose 10 (91%) had >3 markers expressed in CTC (p=0.0274), and 8 (73%) had plasma AR CN gain (p=0.048). A shorter OS was observed in AR-V7+ vs AR-V7- pts [10.6 vs 18.1 mo, HR 2.48 (95% CI 1.00-6.18), p=0.051]. Significantly worse OS and PFS were found in AR CN gain pts compared to AR normal [11.1 mo vs 27.0 mo, HR 2.28 (95% CI 1.19-4.38), p=0.013 and 5.9 mo vs 8.5 mo, HR 1.81 (95% CI 1.05-3.13), p=0.032], respectively. Conclusions: Liquid biopsy profiling may improve prognostication of CRPC patients treated with cabazitaxel. Further larger studies are warranted. Funding: Partially funded by Sanofi Genzyme. Clinical trial information: NCT03381326.

Comparison of abiraterone acetate (Abi) versus ketoconazole (Keto) in patients (pts) with metastatic castration resistant prostate cancer (mCRPC) refractory to docetaxel (D).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e16068-e16068
Author(s):  
Avivit Peer ◽  
Maya Ish-Shalom ◽  
Natalie Maimon ◽  
Maya Gottfried ◽  
Ben Boursi ◽  
...  
Keyword(s):  
Overall Survival ◽  
Cox Regression ◽  
Progression Free Survival ◽  
Risk Category ◽  
Appendicular Skeleton ◽  
Castration Resistant Prostate Cancer ◽  
Time To Progression ◽  
Disease Extent ◽  
Free Survival ◽  
Psa Response

e16068 Background: Abi is a standard treatment (tx) in pts with mCRPC refractory to D. It is a potent and selective CYP 17 inhibitor, that blocks the synthesis of androgens in the testis, adrenal glands, and prostate. However, in many countries where abi has not been approved yet, keto is used as an alternative CYP 17 inhibitor. Although preclinical data suggests that keto is a less specific and potent inhibitor of CYP 17, there are limited clinical data comparing both agents. Aims: To compare the clinical effectiveness of abi vs keto in pts with mCRPC refractory to D. Methods: Records from 156 mCRPC pts treated with keto 200 - 400 mg 3x day, in 4 centers across the US and Israel, were reviewed retrospectively. 26 pts treated post D were individually matched by clinicopathologic factors to pts treated with abi (selected from a multicenter Israeli database, n=120). We compared the PSA response (decrease ≥50% from baseline), biochemical and radiological progression free survival, and overall survival between the groups. Progression free survival and overall survival were determined by Cox regression. Results: The groups were matched by Gleason score, pre-tx disease extent (limited-axial skeleton and/or nodal vs extensive- appendicular skeleton and/or visceral), ECOG PS, pre-tx risk category (favorable, intermediate, poor; Keizman, Oncologist 2012). Furthermore, they were balanced regarding median age (71 abi vs 69 keto), time from primary tx to disease relapse, time to progression on prior GnRH-a and antiandrogen, PSA response and time to progression on prior D, pre-tx pain score/alkaline phosphatase/hemoglobin/neutrophil to lymphocyte ratio/PSADT/PSA. In the groups of abi vs keto, PSA response was 46% vs 19% (OR 4.4, p=0.043), median biochemical PFS 7 vs 2 months (HR 0.65, p=0.02), median radiological PFS 6 vs 2.5 months (HR 0.63, p=0.016), median overall survival 17 vs 12 months (HR 0.53, p=0.79), and tx interruption d/t adverse events 12% vs 23% (0R 0.6, p=0.023). Conclusions: In mCRPC refractory to D, the outcome of pts treated with abiraterone was superior to ketoconazole.

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.

Association of CTC detection by AdnaTest with outcome on enzalutamide in chemotherapy-naïve castration-resistant prostate cancer: Exploratory results from PREMIERE—A SOGUG trial.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 5052-5052 ◽  
Author(s):  
Albert Font Pous ◽  
Sergio Vazquez-Estevez ◽  
Aranzazu Gonzalez del Alba ◽  
Begoña Mellado ◽  
Ovidio Fernandez Calvo ◽  
...  
Keyword(s):  
Gene Expression ◽  
Prostate Cancer ◽  
Clinical Outcome ◽  
Cox Regression ◽  
Castration Resistant Prostate Cancer ◽  
Exact Test ◽  
Castration Resistant ◽  
Expression Studies ◽  
Psa Response ◽  
Gene Expression Studies

5052 Background: Circulating tumor cells (CTCs) enumeration using CellSearch correlates with clinical outcome in prostate cancer, but is limited for gene expression analysis. AdnaTest ProstateCancer is a commercially available CTC immune-enrichment and PCR-related detection method that allows gene expression studies (Antonarakis E, NEJM 2014). It has demonstrated incremental detection of CTCs in patients with no CTCs identified by CellSearch (Samoila A, ASCO 2013) but needs to be clinically qualified. There is a strong need for studies to assess the association with the clinical outcome in CRPC. Methods: Between February and November 2015, 98 asymptomatic or oligo-symptomatic chemotherapy-naïve mCRPC pts were recruited in 16 institutions. Although initially designed to study the predictive value of TMPRSS2-ETS, data emerging after the trial was initiated led the group to prioritize alternative predefined exploratory biomarkers, including plasma AR (Grande E, ASC0 2017 #) and CTC characterization (Grande E, ESMO 2016). Outcome measures included PSA-PFS (sPFS), radiographic PFS (rPFS) and OS. Cox regression was used for survival analyses and Fisher’s exact test for PSA response. Results: Ninety-eight patients had CTC blood samples available. CTCs were detected at baseline, 12 weeks and progression in 36% (35/98), 27% (26/95) and 78% (32/41), respectively. The CTC conversion rate (positive to negative after 12 w) was 43% (15/35). All CTC conversions had ≥50% decline in PSA (15/15) whereas only 35% (7/20) of pts with persistent CTCs. At first interim analysis, with a median follow-up of 10.6 months, detection of CTCs at baseline was associated with worse sPFS (median, 7.59 m versus NR, HR, 3.67; 95% CI 1.90-7.10; P < 0.001), rPFS (median, 12.9 m versus NR; HR, 7.61; 95% CI, 2.80-20.64; P < 0.001) and OS (medians NR, HR, 9.51; 95% CI, 1.11-81.52; P = 0.0398). CTC positive pts were less likely to have a ≥90% decline in PSA (OR, 2.88; 95% CI, 1.13-7.72; P = 0.02). Conclusions: CTC detection using AdnaTest is associated with an adverse outcome in chemotherapy-naïve asymptomatic or oligo-symptomatic mCRPC pts. Clinical trial information: NCT02288936.

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]

ERG rearrangements and association with clinical outcome in patients (pts) receiving abiraterone acetate (AA): Results from the COU-AA-302 study in chemotherapy (chemo)-naïve metastatic castration-resistant prostate cancer (mCRPC).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 5004-5004 ◽  
Author(s):  
Gerhardt Attard ◽  
Johann Sebastian De Bono ◽  
Weimin Li ◽  
Arturo Molina ◽  
Thomas W. Griffin ◽  
...  
Keyword(s):  
Clinical Outcome ◽  
Cox Regression ◽  
Progression Free Survival ◽  
Abiraterone Acetate ◽  
Double Blind Study ◽  
Castration Resistant Prostate Cancer ◽  
Double Blind ◽  
Tissue Samples ◽  
Psa Response ◽  
Psa Progression

5004 Background: ERG rearrangements result in androgen receptor-modulated up-regulation of ERG and may predict for AA response in mCRPC. Concordance has been shown between ERG status in archival samples and fresh CRPC biopsies (Attard et al., Cancer Res. 2009;69:2912). In this prospectively defined biomarker sub-study, the association between ERG subtypes and clinical outcome in chemo-naïve mCRPC pts receiving AA was evaluated. Methods: COU-AA-302 is a randomized double blind study of AA (1 g) + prednisone (P) (5 mg BID) vs placebo + P in chemo-naïve mCRPC. Fluorescence in situ hybridization (FISH) assays to evaluate ERG subtypes (Attard et al., Oncogene. 2008;27:253) were conducted on 524 archival prostate tissue samples (365 biopsies, 107 RPEs, 44 TURPs, 3 bone marrows, 5 lymph nodes) from 497 pts. Clinical outcome measures included radiographic progression-free survival (rPFS) (central [CEN] and investigator [INV] reviewed), time to PSA progression (TTPP), and PSA ≥ 50% decline. Cox regression was used to evaluate association with time to event endpoints and Cochran-Mantel-Haenszel for PSA response. Results: 337 of 497 pts with tumor samples had evaluable FISH results. An ERG rearrangement was present in 117 of 337 (35%) pts. 112 pts were class Edel, 50 were 2+Edel (interstitial deletion with duplication of fusion sequences) and 18 were ESplit. A trend for an association with greater improved rPFS (CEN) and TTPP in 2+ Edel pts treated with AA + P vs ERG non-rearranged was observed (22 months [m] vs 16 m [HR: 0.59, 95% CI: 0.30-1.16], p = 0.12, and 14 m vs 8 m [HR: 0.68; 95% CI: 0.41-1.15], p = 0.15, respectively). No differences in 2+ Edel vs ERG non-rearranged were observed in the P-alone arm. No association between any ERG sub-class and either rPFS [INV] or PSA ≥ 50% decline in either treatment arm was observed. Conclusions: This represents the largest study to date to molecularly characterize CRPC pts participating in a therapeutic phase 3 trial. These data suggest that chemo-naïve mCRPC pts with a 2+ Edel rearrangement may derive a slightly greater benefit from AA and P than other pts. Clinical trial information: NCT00887198.

Association of plasma DNA repair deficient (DRD) status with clinical outcome of metastatic castration-resistant prostate cancer (mCRPC) patients (pts) treated with abiraterone acetate (AA) plus prednisone/dexamethasone (+P/D).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 5066-5066
Author(s):  
Dong Shen ◽  
Shibu Thomas ◽  
Florence Lefresne ◽  
Michael Gormley ◽  
Karen Urtishak ◽  
...  
Keyword(s):  
Cox Regression ◽  
Point Mutations ◽  
Progression Free Survival ◽  
Abiraterone Acetate ◽  
Castration Resistant Prostate Cancer ◽  
Plasma Dna ◽  
Target Capture ◽  
Kaplan Meier ◽  
Genomic Aberrations ◽  
Brca1 Brca2

5066 Background: Somatic DRD deficiency in 15-30% of mCRPC pts have been observed and inhibition of enzyme poly ADP ribose polymerase (PARP) could prove beneficial. We aimed to define DRD status using plasma from pts treated on AA and evaluate associations with prospectively-collected outcome measures. Methods: Plasma DNA samples (128 baseline [BL], 134 cycle 2 day 1 [C2D1], 46 progression [PROG]) from chemotherapy-naïve mCRPC pts in a phase 2 study (NCT01867710) evaluating AA+P/D were subjected to custom target-capture next-generation sequencing. DRD assay was optimized and validated to detect pathogenic point mutations, small insertions/deletions, and copy number alternations (DRD+) in 8 DRD genes: BRCA1, BRCA2, FANCA, ATM, CHEK2, HDAC2, BRIP1, and PALB2. Analysis for genomic aberrations was a secondary exploratory objective. Associations with overall survival (OS), progression-free survival (PFS), and radiographic PFS (rPFS) were assessed using Cox regression models and Kaplan Meier analyses. Results: 11.7% of BL and 17.4% of PROG were DRD+. Bi-allelic was observed in 73.3% of BL DRD+ samples. Shorter PFS was observed in BL DRD+ vs DRD- (5.3 vs 15.5 mo; HR: 2.32; 95%CI:1.39-4.28; P < 0.002). Median PFS for BL DRD biallelic + vs DRD biallelic- was 5.1 vs 15.4 mo (HR: 2.49; 95% CI: 1.23-4.38; P < 0.0095). For multivariate analysis using DRD+, ALP, and LDH as covariates, DRD+ (HR: 2.1; 95% CI: 1.18-3.75; P < 0.012) and high ALP (HR: 1.66; 95% CI: 1.08-2.56; P < 0.021) were strongly associated with worse PFS. Median OS for BL DRD+ vs DRD- was 28.8 vs 41.3 mo (HR: 1.67; 95%CI:0.88-3.18; P = 0.116). Median rPFS for BL DRD+ vs DRD- was 16.2 vs 20.9 mo (HR: 1.64; 95%CI:0.83-3.21; P = 0.152). Of 39 Pts with BL, C2D1 and PROG samples, 3 were DRD+ (7.7%) at all 3 timepoints, 3 (7.7%) only at BL, 3 (7.7%) only at PROG (bi-allelic), 2 (5.1%) had extra deletion at PROG. Conclusions: Patients with mCRPC harboring DRD+ have worse outcomes with AA and represent a population with an unmet medical need.

Eficacy and safety of first-line TKI in elderly with metastatic renal cancer.

2019 ◽  
Vol 37 (7_suppl) ◽  
pp. 588-588 ◽  
Author(s):  
Luciana de Moura Leite ◽  
Jose A. Rinck ◽  
Aldo A. Dettino ◽  
Stenio Cassio Zequi ◽  
Alexandre Andre B. A. Da Costa ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Median Overall Survival ◽  
Kinase Inhibitors ◽  
Cox Regression ◽  
Progression Free Survival ◽  
The Elderly ◽  
Metastatic Renal Cancer ◽  
Free Survival ◽  
Exact Test ◽  
Background Data

588 Background: Data on 1st line treatment with tyrosine kinase inhibitors (TKI) in elderly patients(pts) with metastatic renal cell carcinoma (mRCC) is controversial, and there is rationale for inferior outcomes due to multiple comorbidities and polypharmacy. We aimed to compare the efficacy and safety between the elderly (E) and non-elderly (NE) in 1st line therapy, and to explore factors influencing survival and toxicity. Methods: We retrospectively reviewed all medical records of mRCC pts treated with 1st line TKI at our institution (2007 – 2018). Categorial variables were compared by Fisher’s exact test and continuous, Mann–Whitney. Survival was estimated by Kaplan-Maier method, prognostic factors adjusted by Cox regression model. Results: From 171 eligible pts, 64 (37.4%) had ≥ 65years old, with median age of 70.5 for E and 56 for NE. In both groups most were male, had clear cell histology, good/intermediate IMDC risk, prior nephrectomy and > 1 metastatic (mets) site. Sites of mets were evenly distributed. E pts had more diabetes (35.9 vs16.8%, p.009) , hypertension (67.2 vs 46.7%, p.01), cardiovascular disease (15.6 vs 6.5%, p.06), moderate/severe renal dysfunction (62.5 vs 28.8%, p < 0001), high Charlson Comorbidities Index (CCI≥3, 48.4% vs 20.8%, p < .0001), polypharmacy (34.4 vs15.9%, p.008), worst ECOG (≥2, 28.2 vs 12.3%, p.01), and a trend to worst nutrition (weight loss 35.9 vs 22.5%, p.07). Sunitinib was used for 60.9 vs 79.4%, Pazopanib 35.9 vs 18.7%, Sorafenib 3.1 vs 1.9%, comparing E and NE pts. Median overall survival (OS) and progression free survival (PFS) was 23.7 vs 25.6m (p.8) and 9.3 vs 10.9m (p.7), respectively. After adjusting for prognostic factors, age continues not to influence OS (HR 1.17, IC95 0.77-1.78, p.45). Grade (G) 3/4 toxicity was seen in 59.4 vs 53.3%, dose reduction in 54.7 vs 53.3% and suspension due to toxicity 25 vs 13.3% for E and NE, respectively. In the E, none of the comorbidities, CCI or polypharmacy impaired OS or toxicity, but pts using sunitinibe had greater G3/4 toxicity than with pazopanib (71.8 vs 39.1%, p.02). Conclusions: Elderly had similar outcomes to NE pts, despite greater comorbidities and polypharmacy, hence efficacious therapies shouldn’t avoided. Pazopanib seems to be safer in this subgroup.

Comparison of abiraterone acetate (Abi) versus ketoconazole (Keto) in chemotherapy-naive patients (CN-pts) with metastatic castration resistant prostate cancer (mCRPC).

2016 ◽  
Vol 34 (2_suppl) ◽  
pp. 260-260
Author(s):  
Avivit Peer ◽  
Avivit Neumann ◽  
Avishay Sella ◽  
Eli Rosenbaum ◽  
Victoria Neiman ◽  
...  
Keyword(s):  
Clinical Data ◽  
Cox Regression ◽  
Progression Free Survival ◽  
Clinical Effectiveness ◽  
Axial Skeleton ◽  
Risk Category ◽  
Appendicular Skeleton ◽  
Castration Resistant Prostate Cancer ◽  
Disease Extent ◽  
Psa Response

260 Background: Abi is a standard treatment (tx) in CN-pts with mCRPC. It is a potent and selective CYP 17 inhibitor. However, in many countries where abi has not been approved yet, keto is used as an alternative CYP 17 inhibitor. Preclinical data suggests that keto is a less specific and potent inhibitor of CYP 17. Clinical data (Peer et al, Prostate 2014) suggests that in docetaxel (D) refractory mCRPC, the outcome of abi tx may be superior to keto. However, there are limited clinical data comparing both agents in CN-pts with mCRPC. We aimed to compare the clinical effectiveness of abi vs keto in CN-pts with mCRPC, who were treated after the year 2004 (approval of D for the tx of mCRPC). Methods: Records from 72 CN-pts with mCRPC treated with abi in 5 Israeli centers were reviewed retrospectively, and matched by pre-tx risk category (favorable, intermediate, poor; Keizman, Oncologist 2012) to pts treated with keto 200 - 400 mg 3x day (international database, n = 156, from 4 centers across the US and Israel). We compared the PSA response (decrease ≥ 50% from baseline), biochemical and radiological progression free survival (PFS), and overall survival (OS) between the groups. PFS and OS were determined by Cox regression. Results: The groups were matched by pre-tx risk category (favorable, intermediate, poor; Keizman, Oncologist 2012), based on pretreatment NLR and PSA doubling time, and the prior response to a gonadotropin-releasing hormone agonist. The groups were balanced regarding age (72 abi vs 70 keto), time from primary tx to disease relapse, gleason score, pre-tx disease extent (limited-axial skeleton and/or nodal vs extensive- appendicular skeleton and/or visceral), and ECOG PS. In the groups of abi vs keto, PSA response was 75% vs 47% (OR 3.8, p = 0.04), median biochemical PFS 12 vs 6 months (HR 0.62, p = 0.03), median radiological PFS 16 vs 8 months (HR 0.54, p = 0.01), median OS not reached after a median follow-up time of 18 months vs 26 months, and tx interruption d/t adverse events 10% vs 22% (0R 0.65, p = 0.05). Conclusions: In CN-pts with mCRPC, the outcome of pts treated with abi may be superior to keto.

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