Prognostic value of neutrophil-to-lymphocyte ratio (NLR) in pts with metastatic castration-resistant prostate cancer (mCRPC) receiving a new agent (NA)- based third-line treatment: Final results from a multicenter Italian study.

2017 ◽  
Vol 35 (6_suppl) ◽  
pp. 230-230
Author(s):  
Orazio Caffo ◽  
Emilio Bria ◽  
Ugo De Giorgi ◽  
Marcello Tucci ◽  
Luca Galli ◽  
...  

230 Background: High NLR has been reported to be a poor prognostic indicator in both first and second mCRPC lines, while no information is available concerning this issue in pts treated in third line therapy. The present study is aimed to assess the possible relationship between third line clinical outcomes and NLR in a series of mCRPC pts treated with a NA [abiraterone acetate (AA), cabazitaxel (CABA), or enzalutamide (ENZ)] after the failure of docetaxel (DOC) and another NA. Methods: We collected data of pts who received sequentially two NAs after DOC in 38 Italian hospitals. For each pt we recorded the clinical outcome of all treatments received after DOC. Cox regression analysis was used to assess the independent prognostic value of a series of pretreatment covariates, in terms of overall survival (OS), comprising NLR. Results: A consecutive series of 476 mCRPC pts with bone (86%), nodal (56%) or visceral (15%) mets, was collected. All pts received a NA-based third line: 135 received AA, 221 CABA and 120 ENZ. Data on NLR were available for 398 pts (84%). In the univariate analyses, the NLR as a discrete variable dichotomized according to the Maximally Selected Log-Rank statistics (optimal cut-off: 3.66), was significantly associated with both OS and progression free survival (PFS), calculated from the third line start (p < 0.0001). At the multivariate analysis, NLR, performance status, pain, hemoglobin, alkaline phosphatase, treatment with AA and with CABA were independent prognostic factors for PFS, while NLR, performance status, hemoglobin, PSA, and lactate dehydrogenase were independent prognostic factors for OS . In Kaplan-Meier analysis, the median OS from the start of third-line was higher (14.2 vs 9.3 mos) in pts with NLR ≤ 3.1 compared to those with NLR > 3.1 (log-rank; P < 0.0001). Similarly, the median PFS was 5.5 and 3.8 (log-rank; P < 0.0001) in pts with NLR ≤ 3.66 and > 3.66, respectively. Conclusions: Our results, observed in the largest cohort of mCRCP pts treated with NA-based third line after DOC and another NA, confirms that NLR is an independent factor for PFS and OS also in this population.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e16521-e16521
Author(s):  
Orazio Caffo ◽  
Emilio Bria ◽  
Ugo De Giorgi ◽  
Marcello Tucci ◽  
Elisa Biasco ◽  
...  

e16521 Background: High NLR has been reported to be a poor prognostic indicator in both first and second mCRPC lines, while no information is available concerning this issue in pts treated in third line therapy. The present study is aimed to assess the possible relationship between third line clinical outcomes and NLR in a series of mCRPC pts treated with a NA [abiraterone acetate (AA), cabazitaxel (CABA), or enzalutamide (ENZ)] after the failure of docetaxel (DOC) and another NA. Methods: We collected data of pts who received sequentially two NAs after DOC in 38 Italian hospitals. For each pt we recorded the clinical outcome of all treatments received after DOC. Cox regression analysis was used to assess the independent prognostic value of a series of pretreatment covariates, in terms of overall survival (OS), comprising NLR. Results: A consecutive series of 476 mCRPC pts with bone (86%), nodal (56%) or visceral (15%) mets, was collected. All pts received a NA-based third line: 135 received AA, 221 CABA and 120 ENZ. Data on NLR were available for 398 pts (84%). In the univariate analyses, the NLR as a discrete variable dichotomized according to the Maximally Selected Log-Rank statistics (optimal cut-off: 3.66), was significantly associated with both OS and progression free survival (PFS), calculated from the third line start (p < 0.0001). At the multivariate analysis, NLR, performance status, pain, hemoglobin, alkaline phosphatase, treatment with AA and with CABA were independent prognostic factors for PFS, while NLR, performance status, hemoglobin, PSA, and lactate dehydrogenase were independent prognostic factors for OS. In Kaplan-Meier analysis, the median OS from the start of third-line was higher (14.2 vs 9.3 mos) in pts with NLR ≤ 3.1 compared to those with NLR > 3.1 (log-rank; P < 0.0001). Similarly, the median PFS was 5.5 and 3.8 (log-rank; P < 0.0001) in pts with NLR ≤ 3.66 and > 3.66, respectively. Conclusions: Our results, observed in the largest cohort of mCRCP pts treated with NA-based third line after DOC and another NA, confirms that NLR is an independent factor for PFS and OS also in this population.


2016 ◽  
Vol 34 (2_suppl) ◽  
pp. 211-211
Author(s):  
Orazio Caffo ◽  
Ugo De Giorgi ◽  
Daniele Alesini ◽  
Lucia Fratino ◽  
Cinzia Ortega ◽  
...  

211 Background: The NLR is a marker of systemic inflammatory response: several studies investigated its prognostic relevance in mCRPC but to date no information is available concerning this issue in pts treated in third line therapy. The present study is aimed to assess the possible relationship between third line clinical outcome and NLR in a large series of mCRPC pts treated with a NA [abiraterone acetate (AA), cabazitaxel (CABA), or enzalutamide (ENZ)] after the failure of docetaxel (DOC) and another NA. Methods: We collected data of pts who received sequentially two NAs after DOC in 38 Italian hospitals. For each pt we recorded the clinical outcome of all treatments received after DOC. Cox regression analysis was used to assess the independent prognostic value of a series of pretreatment covariates, in terms of overall survival (OS), comprising NLR. Results: A consecutive series of 291 mCRPC pts with bone (88%), nodal (53%) or visceral (18%) mets, was collected. All pts received a NA-based third line: 90 received AA, 123 CABA and 78 ENZ. At the time of this analysis, data on NLR were available for 198 pts (68%): AA 68 (75%) – CABA 80 (65%) – ENZ 50 (64%): the median value was 3.1 (IQR 2.2-4.7). In the univariate analyses, the NLR as a discrete variable using the median value of 3.1 as threshold, was significantly associated with both OS and progression free survival (PFS), calculated from the third line start (p < 0.0001 and p = 0.001, respectively). No association was observed with either biochemical or objective response. These results were confirmed at the multivariate analysis. In Kaplan-Meier analysis, the median OS from the start of third-line was higher (18.2 vs 8.1 mos) in pts with NLR ≤ 3.1 compared to those with NLR > 3.1 (log-rank; P < 0.0001). Similarly, the median PFS was 6.3 and 3.5 in pts with NLR ≤ 3.1 and > 3.1, respectively. Conclusions: At the best of our knowledge, this is the first report on the NLR value in mCRPC third line treatment. From our preliminary data, it appears that NLR may be a prognostic and predictive factor in mCRPC pts, treated with NA-based third line.


2020 ◽  
Vol 21 (13) ◽  
pp. 919-928
Author(s):  
Ana Afonso ◽  
Jani Silva ◽  
Ana Rita Lopes ◽  
Sara Coelho ◽  
Ana Sofia Patrão ◽  
...  

Aim: To evaluate the influence of YB-1 rs10493112 variant as a genetic marker for response to second-generation androgen receptor axis-target agents. Methods: A hospital-based cohort study of 78 patients with metastatic castration-resistant prostate cancer was conducted. Genotyping was performed by TaqMan® allelic discrimination technology. Main results: In abiraterone-treated and high-risk patients, YB-1 rs10493112 AA genotype carriers showed lower progression-free survival than C allele genotype patients (4 vs 17 months; p = 0.009). For carriers of AA genotype, multivariate Cox regression analysis revealed a fivefold increased risk of progression (p = 0.035). Conclusion: The study findings suggest that, for metastatic and castration-resistant prostate cancer patients, this polymorphism might be a putative marker for the clinical outcome.


2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 4500-4500
Author(s):  
R. T. Shroff ◽  
M. M. Javle ◽  
X. Dong ◽  
V. S. Kumar ◽  
S. Krishnan ◽  
...  

4500 Background: The IGFR pathway is activated in pancreatic cancer and may result in aggressive disease course. The study of single nucleotide polymorphisms (SNPs) involved in this pathway may provide prognostic information and predict response to IGFR directed agents. We investigated IGFR pathway SNPs in patients with LAPC. Methods: We evaluated 39 SNPs from 7 candidate genes in the IGFR pathway (IGF1R, IGF2R, IGF1, IGF2, IRS1, IRS2, IGFBP3) in 105 LAPC patients. DNA extraction from whole blood was performed using the Qiagen Flexigene DNA and Promega Maxwell 16 kits. Genotyping was performed using the Sequenom method. Overall survival was measured from date of diagnosis to date of death or last follow-up. Kaplan-Meier plot, log-rank test, and Cox regression were used to compare survival of patients according to genotype corrected for previously identified prognostic factors, including induction chemotherapy, CA 19–9, albumin, LDH, hemoglobin and Karnofsky performance status (KPS). Results: Median survival time (MST) was 15 months (95% CI 13.3–16.7). Induction chemotherapy, LDH, CA 19–9 level, hemoglobin, and KPS were not significantly associated with survival. Serum albumin and three SNPs of the IGF pathway (IGF1R IVS20–3431A>G, IRS1 G971R, and IGF2 *4352A>G) were significantly associated with prognosis ( Table ). Two of the three genotypes remained as significant predictors for survival in Cox regression analysis when adjusted for clinical factors. A significant combined genotype effect was observed wherein patients with all three deleterious alleles had significantly worse survival than those with only two or one (10 vs. 16.3 vs. 21.3 months, p< 0.0001). Conclusions: These data suggest that SNPs in the IGFR pathway genes may have prognostic value for LAPC patients. This information may identify population subgroups that could benefit from IGFR-targeted agents. [Table: see text] No significant financial relationships to disclose.


2014 ◽  
Vol 32 (4_suppl) ◽  
pp. 216-216 ◽  
Author(s):  
Rosa Nadal ◽  
Zhe Zhang ◽  
Hitesh Raheja ◽  
Mario A. Eisenberger ◽  
Emmanuel S. Antonarakis

216 Background: Enzalutamide is an androgen receptor signaling inhibitor that is FDA-approved for post-docetaxel mCRPC patients. Overlapping mechanisms of action and clinical evidence for an interaction between taxanes and androgen-targeted therapies complicates optimal sequencing of taxanes and enzalutamide. We retrospectively evaluated the efficacy of enzalutamide pre- (preD) and post-docetaxel (postD) therapy. Methods: Men with mCRPC who received enzalutamide preD or postD were identified from a single institution database. We investigated factors influencing enzalutamide activity by using univariate and multivariable Cox regression models, with particular attention to whether or not prior docetaxel had been used. Outcome measures of interest were time-to-PSA-progression (TTPP) and progression-free-survival (PFS). Results: A total of 72 patients received enzalutamide at our institution: 22 were preD and 50 were postD. Median duration of enzalutamide therapy was 5.5 mo (range, 0.7–33.6 mo). In univariate Cox regression analysis, the following factors were predictive of TTPP: ECOG status (≥1 vs 0), number of metastases (>5 vs 0-5), hemoglobin and albumin. Prior docetaxel treatment was associated with a trend towards shorter TTPP on enzalutamide (HR 0.54, 95%CI 0.27–1.10, P=0.09). The following factors were predictive of PFS in univariate analysis: ECOG status, number of metastases, hemoglobin and albumin. Prior docetaxel therapy was associated with a trend towards shorter PFS on enzalutamide (HR 0.57, 95%CI 0.29–1.13, P=0.10). Conclusions: These data suggest numerically inferior TTPP and PFS outcomes to enzalutamide in men previously treated with docetaxel compared to men who were docetaxel-naïve, although the small sample size precludes statistically significant results. This potentially supports the hypothesis of cross-resistance between enzalutamide and docetaxel.


2015 ◽  
Vol 33 (7_suppl) ◽  
pp. 216-216
Author(s):  
Orazio Caffo ◽  
Ugo De Giorgi ◽  
Gaetano Facchini ◽  
Lucia Fratino ◽  
Donatello Gasparro ◽  
...  

216 Background: The androgen receptor machinery remains the ultimate target of NAs in mCRPC post-DOC, abiraterone acetate (AA), cabazitaxel (CAB), and enzalutamide (ENZ). It is postulated that some mechanisms of resistance may be common to all NAs. This may be crucial in planning their sequential use, mainly when a PRes to one of them is observed. The present study assessed the activity of NAs in pts who previously experienced a PRes to another NA administered after DOC. Methods: We collected data of pts who received sequentially two NAs after DOC in 32 Italian hospital. For each pt we recorded the clinical outcomes of all treatments received after DOC. For the study purpose, we consider with PRes all pts progressing within 3 months after second line NA start. All other pts were considered as without PRes. Results: A consecutive series of 271 mCRPC pts, median age 71 yrs (46-91), with bone (89%), nodal (56%) or visceral (19%) mets, was collected. All pts received NAs as second line after DOC (AA 54% – CAB 34%– ENZ 12%) and 54 (20%) showed a PRes. Among these, third line treatment [AA (31%), CAB (42%), and ENZ (27%)], produced a biochemical and an objective response rate of 11% in both cases, with a median progression free survival (PFS) and a median overall survival (OS) of 4 mos and 8 mos, respectively. No statistically significant differences were observed in terms of clinical outcomes on the basis of NA sequences (see Table). Conclusions: It appears from this preliminary data, that the activity of NAs in pts showing a PRes to second line NAs is very limited, regardless the NA is administered. [Table: see text]


2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e16541-e16541
Author(s):  
David Lorente ◽  
Rebeca Lozano ◽  
Guillermo de Velasco ◽  
Maria De Julian ◽  
Miguel Rodrigo ◽  
...  

e16541 Background: PSA is a widely used biomarker for monitoring outcome in mCRPC. Current treatment guidelines do not consider PSA progression before at least 12 weeks of treatment, and recommend treatment continuation in pts experiencing progression by PSA only, without radiographic or clinicall progression. We aimed to evaluate the prognostic value of a PSA progression in mCRPC pts treated with first-line therapy. Methods: We analyzed the value of a PSA progression (PSAProg) at cycle 5 in pts treated in the COU-AA-302 trial. PSAProg was defined as an increase ≥ 25% and ≥ 2 ng/mL from baseline, confirmed by a second reading. Radiographic progression (RadProg) was defined as per PCWG2 criteria for bone scan or RECIST progression. Survival and radiographic progression-free survival (rPFS) from the time of PSAProg was calculated using Kaplan-Meier estimates. Cox-regression models were used to evaluate the impact of PSAProg and treatment arm on survival. Results: 1088 pts were randomized in the COU-AA-302 trial. 908 pts (83.5%) had valid baseline and cycle 5 PSA values. Of these, 222 (24.4%) pts experienced PSAProg, which was confirmed in 195 (21.5%) pts; 45/479 (9.4%) of abiraterone and 150/429 (35%) of placebo-treated pts. A confirmed PSAProg was associated with shorter survival (37.8 vs 26m; HR: 1.8; p < 0.001) and rPFS (13.9 vs 5.6m; HR:2.1; p < 0.001). Median survival from the time of PSAProg was 22.2m (95%CI:18.9-25.4). Abiraterone-treated pts had a significantly longer survival from the time of PSAProg (23.1 vs 17.4m; HR: 0.64; p = 0.018). 111 pts (56,9%) experienced PSAprog without RadProg; in pts with PSAprog only, median time to RadProg was 7.4m (95%CI:7.1-12.9). No differences in rPFS from the time of PSAprog were observed in abiraterone vs placebo-treated pts (HR: 0.99; p = 0.963). Conclusions: 9.4% of abiraterone-treated pts in the COU-AA-302 trial experienced PSAProg at 12 weeks (cycle 5 day 1). PSAProg was associated with significantly worse survival. Abiraterone increased survival from the time of PSAProg, which supports its continued use in pts with PSA progression only at 12 weeks. This study was carried out under YODA Project #2018-3011.


2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 5569-5569
Author(s):  
Bertrand F. Tombal ◽  
Daniel Castellano ◽  
Gero Kramer ◽  
Jean-Christophe Eymard ◽  
Johann S. De Bono ◽  
...  

5569 Background: The CARD trial (NCT02485691) compared cabazitaxel vs. an androgen receptor targeted agent (ART; abiraterone/enzalutamide) in mCRPC previously treated with docetaxel and the alternative ART (abiraterone/enzalutamide), in any order. These post hoc analyses assessed OS from various time points and the impact of prognostic factors. Methods: Patients with mCRPC previously treated with docetaxel and progressing ≤ 12 months on prior abiraterone/enzalutamide were randomized 1:1 to cabazitaxel (25 mg/m2 IV Q3W + daily prednisone + prophylactic G-CSF) vs. abiraterone (1000 mg PO + daily prednisone) or enzalutamide (160 mg PO). OS was calculated from date of diagnosis of metastatic disease, date of mCRPC, and start of 1st, 2nd or 3rd life-extending therapy (LET). A stratified multivariate Cox regression analysis assessed the impact of 14 prognostic factors on OS using a stepwise model selection approach with a significance level of 0.10 for entry into the model and 0.05 for removal. Results: In the CARD study (N = 255), median OS was longer with cabazitaxel vs. abiraterone/enzalutamide (13.6 vs 11.0 months; HR 0.64, 95% CI 0.46–0.89; p = 0.008). OS was numerically improved for cabazitaxel vs. abiraterone/enzalutamide when assessed from the time of diagnosis of metastatic disease or mCRPC, or from start of 1st or 2nd LET (Table). In the multivariate analysis, low hemoglobin, high baseline neutrophil to lymphocyte ratio, and high PSA values at baseline were associated with worse OS. In presence of these factors, the OS benefit observed with cabazitaxel versus abiraterone/enzalutamide remained significant (HR 0.63, 95% CI 0.42–0.94, p = 0.022). Conclusions: Cabazitaxel numerically improved OS vs. abiraterone/enzalutamide in patients with mCRPC previously treated with docetaxel and the alternative ART (abiraterone/enzalutamide), whatever the time point considered. The robustness of this OS benefit was confirmed by stratified multivariate analysis. Sanofi funded. Clinical trial information: NCT02485691 . [Table: see text]


2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e15131-e15131 ◽  
Author(s):  
Camilla Stedstrup Mosgaard ◽  
Mathias Holsey Gramkow ◽  
Christian Dehlendorff ◽  
Dorte Nielsen ◽  
Per Pfeiffer ◽  
...  

e15131 Background: CEA is regarded as the marker of choice for monitoring patients with colorectal cancer (CRC), but the value of using CA19-9 is insufficient. The prognostic value of serum CA19-9 in combination with CEA was evaluated in patients with metastatic CRC (mCRC) before first (1) and third line therapy (3LT). Methods: From April 2004 to May 2015, pretreatment serum samples were collected from 160 and 255 patients with mCRC before 1LT and 3LT, respectively. Median age was 64 [range 33-87] and male/female ratio 243(59%)/172(41%). Serum CA19-9 was determined by routine chemiluminescent immunometric assay (normal range 0-37 KU/l). Progression-free survival (PFS) and overall (OS) crude, adjusted hazard ratios (HR) and corresponding 95% confidence intervals (CIs) were estimated using Cox regression analysis. CA19-9 and CEA were included as log2-transformed continuous variables and adjustment included mutually between CA19-9 and CEA in addition to primary tumor location, sex and age. Results: In 3LT median pretreatment CEA levels were higher than in 1LT (59 µg/l [IQR 14-288] vs. 23[6-153] P < 0.01) while CA19-9 values were similar (112 KU/l [23-626] vs. 98[19-390]). In patients treated with 3LT univariate analysis showed that high levels of CA19-9 and CEA were associated with short PFS (CA19-9: HR = 1.06, 95% CI 1.02-1.10, P < 0.01; CEA: HR = 1.05, 1.00-1.09, P = 0.04). In 1LT neither CA19-9 nor CEA were significantly associated with PFS. In a multivariate analysis, none of the biomarkers were significantly associated with PFS. In patients treated with 3LT univariate analysis showed that high levels of CA 19-9 and CEA were associated with short OS (CA19-9: HR = 1.11, 1.07-1.16, P < 0.01; CEA: HR = 1.1, 1.06-1.16, P < 0.01). In patients treated with 1LT high levels of CA-19-9 but not CEA was significantly associated with a shorter OS (HR = 1.07, 1.00-1.14, P = 0.04). In 3LT multivariate analyses showed that high levels of CA19-9 and CEA were the only factors associated with a shorter OS (CA19-9: HR = 1.08, 1.03-1.13, P < 0.01; CEA: HR = 1.07, 1.01-1.14, P < 0.01), while there was no significant association to OS in 1LT. Conclusions: Serum CA19-9 may be a valuable prognostic biomarker in combination with CEA in mCRC patients receiving third line therapy.


2017 ◽  
Vol 35 (6_suppl) ◽  
pp. e585-e585
Author(s):  
Orazio Caffo ◽  
Emilio Bria ◽  
Ugo De Giorgi ◽  
Marcello Tucci ◽  
Elisa Biasco ◽  
...  

e585 Background: Several NA [abiraterone acetate (AA), cabazitaxel (CABA), or enzalutamide (ENZ)] changed the prognosis of mCRPC pts being able to significantly prolong their overall survival (OS) after docetaxel failure. Unfortunately, a quote of pts experiences an early progression (within 3 mos) during the second line treatment and it is unclear if a clinical benefit may result from a subsequent treatment with another NA. The present study is aimed to assess the clinical outcomes and prognostic factors of subsequent NA treatment in those pts PR to the second line NA. Methods: We collected data of pts who received sequentially two NAs after DOC in 38 Italian hospitals. For each pt we recorded the clinical outcome of all treatments received after DOC. For the purpose of the present analysis we consider as PR pts who progressed within 3 months from the start of the NA second line. Cox regression analysis was used to assess the independent prognostic value of a series of third-line baseline covariates, in terms of progression free survival (PFS) and OS. Results: A consecutive series of 476 mCRPC pts with bone (86%), nodal (56%) or visceral (15%) mets, was collected. The NA-based second line consisted of AA (261 pts), CABA (151), and ENZ (64): we identified 55 PR pts (AA 24 – CABA 24 – ENZ 7). All pts received a subsequent NA-based third line: 22 received AA, 25 CABA, and 8 ENZ. Compared to no-PR pts, PR pts showed a lower biochemical response rate (12.2% vs 31.6%; p = 0.005), but no significant differences in terms of objective response rate (17.1% vs 15.2%), PFS (median 3.5 vs 4.7 mos), and OS (median 9.4 vs 12.9 mos). Considering the PR population, at the multivariate analysis , lactate dehydrogenase and PSA were independent prognostic factors for PFS in third line, while hemoglobin, PSA, administration of one NA in fourth line and lactate dehydrogenase were independent prognostic factors for OS. Conclusions: In our experience, NA-based third line is active also in mCRPC PR population and some factors may help in selecting patients with higher probability of achieving a disease control.


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