SLFN11 expression (exp) in castration-resistant prostate cancer (CRPC) patients (pts) to predict response to platinum-based chemotherapy (PLT).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 5065-5065
Author(s):  
Vincenza Conteduca ◽  
Loredana Puca ◽  
Sheng-Yu Ku ◽  
Judy Hess ◽  
Megan Kearney ◽  
...  
Keyword(s):  
Cox Regression ◽  
Multivariable Analysis ◽  
Progression Free Survival ◽  
Predictive Biomarker ◽  
Median Number ◽  
Parp Inhibitors ◽  
Castration Resistant Prostate Cancer ◽  
Cox Regression Analysis ◽  
Platinum Based Chemotherapy

5065 Background: Schlafen family member 11 (SLFN11) sensitizes tumor cells to DNA-damaging agents and has been investigated as a potential predictive biomarker of response to PLT and PARP inhibitors, especially in small cell lung cancer (Lok, CCR 2017; Pietanza, JCO 2018). We aimed to explore the predictive/prognostic role of SLFN11 in PLT-treated CRPC. Methods: We assessed tumor exp of SLFN11 in PLT-treated, metastatic CRPC pts by RNAseq (N=27) and/or CTCs (N=20) (via the Epic Sciences platform). In addition, tumor morphology for neuroendocrine (NE) features and genomic status of select genes (ie, AR, TP53, RB1, BRCA2, BRCA1, ATM) by whole exome sequencing were evaluated. Statistical comparisons used Cox regression analysis and Kaplan Meier method for the association with overall/radiographic progression free survival (OS/rPFS). A dose response curve with PLT was performed in patient-derived organoids using Cell Title Glo according to the manufacturer’s protocol. Results: 41 CRPC (including 20 CRPC-NE) treated with PLT monotherapy (N=3) or PLT combination therapy (N=38) between August 2013 and December 2017 were evaluated. Median age was 67.1 years (range 51-91). Median number of prior therapies was 2 (range 1-7). A longer median rPFS was observed in all SLFN11+ pts treated with PLT (regardless of histology, RB1, TP53, PTEN, or DNA repair status) compared to SLFN11- [5.2 vs 2.3 months, HR 3.5, 95%CI 1.6-7.7, P<0.0001]. No association was reported for OS. On multivariable analysis (Table), SLFN11 was an independent factor associated with rPFS. Organoids derived from patient tumors expressing SLFN11 showed sensitivity to PLT in vitro. Conclusions: SLFN11 exp identifies both CRPC and CRPC-NE pts with a better response to PLT. Patient-derived organoids expressing SLFN11 confirmed increased sensitivity to PLT. Larger prospective evaluation of therapy decisions based on SLFN11 exp is now required. [Table: see text]

scholarly journals Clinical relevance of kallikrein-related peptidase 6 (KLK6) and 8 (KLK8) mRNA expression in advanced serous ovarian cancer

2016 ◽  
Vol 397 (12) ◽  
pp. 1265-1276 ◽  
Author(s):  
Nancy Ahmed ◽  
Julia Dorn ◽  
Rudolf Napieralski ◽  
Enken Drecoll ◽  
Matthias Kotzsch ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Mrna Expression ◽  
Cox Regression ◽  
Multivariable Analysis ◽  
Progression Free Survival ◽  
Predictive Marker ◽  
Residual Tumor ◽  
Mrna Levels ◽  
Serous Ovarian Cancer ◽  
Cox Regression Analysis

Abstract Most members of the kallikrein-related peptidase family have been demonstrated to be dysregulated in ovarian cancer and modulate tumor growth, migration, invasion, and resistance to chemotherapy. In the present study, we assessed the mRNA expression levels of KLK6 and KLK8 by quantitative PCR in 100 patients with advanced serous ovarian cancer FIGO stage III/IV. A pronounced correlation between KLK6 and KLK8 mRNA expression (rs = 0.636, p < 0.001) was observed, indicating coordinate expression of both peptidases. No significant associations of clinical parameters with KLK6, KLK8, and a combined score KLK6+KLK8 were found. In univariate Cox regression analysis, elevated mRNA levels of KLK6 were significantly linked with shortened overall survival (OS) (hazard ratio [HR] = 2.07, p = 0.007). While KLK8 values were not associated with patients’ outcome, high KLK6+KLK8 values were significantly associated with shorter progression-free survival (HR = 1.82, p = 0.047) and showed a trend towards significance in the case of OS (HR = 1.82, p = 0.053). Strikingly, in multivariable analysis, elevated KLK6 mRNA values, apart from residual tumor mass, remained an independent predictive marker for poor OS (HR = 2.33, p = 0.005). As KLK6 mRNA and protein levels correlate, KLK6 may represent an attractive therapeutic target for potent and specific inhibitors of its enzymatic activity.

YB-1 variant and androgen receptor axis-targeted agents in metastatic castration-resistant prostate cancer patients

2020 ◽  
Vol 21 (13) ◽  
pp. 919-928
Author(s):  
Ana Afonso ◽  
Jani Silva ◽  
Ana Rita Lopes ◽  
Sara Coelho ◽  
Ana Sofia Patrão ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Androgen Receptor ◽  
Cancer Patients ◽  
Cox Regression ◽  
Progression Free Survival ◽  
Castration Resistant Prostate Cancer ◽  
Allelic Discrimination ◽  
Cox Regression Analysis ◽  
Castration Resistant ◽  
Increased Risk

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.

scholarly journals mTOR Pathway Expression as Potential Predictive Biomarker in Patients with Advanced Neuroendocrine Tumors Treated with Everolimus

Cancers ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 1201 ◽  
Author(s):  
Fabio Gelsomino ◽  
Andrea Casadei-Gardini ◽  
Francesco Caputo ◽  
Giulio Rossi ◽  
Federica Bertolini ◽  
...  
Keyword(s):  
Neuroendocrine Tumors ◽  
Cox Regression ◽  
Progression Free Survival ◽  
Predictive Biomarker ◽  
Mtor Pathway ◽  
Cox Regression Analysis ◽  
Pathway Expression ◽  
Group 2 ◽  
Tissue Specimens ◽  
Group 1

Background. Everolimus (Eve), which is a mammalian target of Rapamicin (mTOR) inhibitor, is part of the therapeutic armamentarium of neuroendocrine tumors (NETs). Currently, there are no validated biomarkers predicting Eve efficacy in NETs. In this study, we explore whether the expression of phosphorilated (p)-mTOR and p70S6-kinase (S6K), a downstream effector of mTOR, correlates with the outcome of patients with NET that were treated with Eve. Methods. Tissue specimens that were derived from NETs treated with Eve at our Institution were examined for the expression levels of p-mTOR and p-S6K by immunohistochemistry. Response rate (RR), progression-free survival (PFS), and overall survival (OS) were analyzed in two groups: p-mTOR/p-S6K positive (group 1) and p-mTOR/p-S6K negative (group 2). Univariate and multivariate Cox regression analysis were performed. Results. Twenty-four patients with advanced NETs that were treated with Eve were included in the analysis. Eight out 24 (33.3%) patients were both p-mTOR and p-S6K positive. A better median PFS and OS in group 1 (18.2 and 39.9 months) as compared to group 2 (13 and 32.4 months) was depicted, with a toxicity profile that was comparable with data literature. Conclusions. Our study suggests that the activation of mTOR pathway can predict better outcomes in patients with NET treated with Eve. However, these results warrant further confirmation in a prospective setting.

Clinical activity of enzalutamide pre- and post-docetaxel in patients with metastatic castration-resistant prostate cancer (mCRPC).

2014 ◽  
Vol 32 (4_suppl) ◽  
pp. 216-216 ◽  
Author(s):  
Rosa Nadal ◽  
Zhe Zhang ◽  
Hitesh Raheja ◽  
Mario A. Eisenberger ◽  
Emmanuel S. Antonarakis
Keyword(s):  
Cox Regression ◽  
Small Sample Size ◽  
Univariate Analysis ◽  
Progression Free Survival ◽  
Small Sample ◽  
Cross Resistance ◽  
Clinical Activity ◽  
Castration Resistant Prostate Cancer ◽  
Cox Regression Analysis ◽  
Docetaxel Treatment

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.

A prognostic score for patients with metastatic castration-resistant prostate cancer treated with abiraterone acetate post chemotherapy.

2014 ◽  
Vol 32 (4_suppl) ◽  
pp. 70-70 ◽  
Author(s):  
Arnoud J. Templeton ◽  
Aurelius Gabriel Omlin ◽  
Carmel Jo Pezaro ◽  
Thian San Kheoh ◽  
Raya Leibowitz-Amit ◽  
...  
Keyword(s):  
Cox Regression ◽  
Prognostic Score ◽  
Multivariable Analysis ◽  
Risk Groups ◽  
P Value ◽  
Castration Resistant Prostate Cancer ◽  
Data Set ◽  
Cox Regression Analysis ◽  
Neutrophil Lymphocyte Ratio ◽  
Visceral Disease

70 Background: We aimed to establish a simple prognostic score for men with mCRPC treated with abiraterone following docetaxel and explored incorporation of the neutrophil/lymphocyte ratio (NLR), a marker of host inflammation with prognostic value in many solid tumors. Methods: To develop the model, clinical and laboratory factors for 185 men treated at Royal Marsden were included in a univariable Cox regression analysis. Statistically significant variables were dichotomized using an optimal cut-off chosen by selecting the highest c-index among three potential cut-offs with high Hazard Ratios (HR). All significant variables in univariable analysis were analyzed using multivariable Cox analysis. One risk point was assigned for each variable with a P value of <0.05 in multivariable analysis and the risk points were used to establish three prognostic groups of similar prevalence. The validity of the model is being examined using the large data-set from the abiraterone registration trial (COU-AA-301). Results: Median age was 69 years, 41% had both bone and lymph node metastases (BLN), 15% had visceral disease. Involvement of BLN or visceral disease (HR 1.6, P=0.013), ALP >2.0 x ULN (HR 1.7, P=0.005), LDH >1.5 x ULN (HR 3.4, P<0.001), Hgb <12 g/dL (HR 2.1, P<0.001), and NLR >5 (HR 1.5, P=0.033) were associated with worse OS in the multivariable analysis. Outcomes for three risk groups using these 5 factors are presented in the table. The c-index was 0.73 (95% CI 0.65 - 0.80) for the prognostic score. Patients with NLR >5 at baseline and whose NLR was ≤5 within four weeks of treatment also had longer median survival (15.1 months) than those with NLR >5 at baseline that remained high (median OS 7.6 months, HR 0.48, 95% CI 0.25-0.93, P=0.029). Conclusions: This initial simple risk score provides good prognostic and discriminatory accuracy for men with mCRPC. Data from the validation cohort will be presented. [Table: see text]

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

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e16521-e16521
Author(s):  
Orazio Caffo ◽  
Emilio Bria ◽  
Ugo De Giorgi ◽  
Marcello Tucci ◽  
Elisa Biasco ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Prognostic Value ◽  
Cox Regression ◽  
Performance Status ◽  
Progression Free Survival ◽  
Prognostic Indicator ◽  
Consecutive Series ◽  
Castration Resistant Prostate Cancer ◽  
Cox Regression Analysis ◽  
Third Line

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.

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 ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Prognostic Value ◽  
Cox Regression ◽  
Performance Status ◽  
Progression Free Survival ◽  
Prognostic Indicator ◽  
Consecutive Series ◽  
Castration Resistant Prostate Cancer ◽  
Cox Regression Analysis ◽  
Third Line

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.

scholarly journals Salvage therapies for radiation-relapsed IDH-mutant astrocytoma and 1p/19q codeleted oligodendroglioma

2021 ◽  
Author(s):  
Sirui Ma ◽  
Soumon Rudra ◽  
Jian L Campian ◽  
Milan G Chheda ◽  
Tanner M Johanns ◽  
...  
Keyword(s):  
Cox Regression ◽  
Salvage Surgery ◽  
Multivariable Analysis ◽  
Progression Free Survival ◽  
Cancer Center ◽  
First Line ◽  
Free Survival ◽  
Cox Regression Analysis ◽  
Kaplan Meier ◽  
Tertiary Cancer Center

Abstract Background Optimal management for recurrent IDH-mutant glioma after radiation therapy (RT) is not well-defined. This study assesses practice patterns for managing recurrent IDH-mutant astrocytoma (Astro) and 1p/19q codeleted oligodendroglioma (Oligo) after RT and surveys their clinical outcomes after different salvage approaches. Methods Ninety-four recurrent Astro or Oligo patients after RT who received salvage systemic therapy (SST) between 2001 and 2019 at a tertiary cancer center were retrospectively analyzed. SST was defined as either alkylating chemotherapy (AC) or non-alkylating therapy (non-AC). Overall survival (OS) and progression-free survival (PFS) were calculated using the Kaplan-Meier method from the start of SST. Multivariable analysis (MVA) was conducted using Cox regression analysis. Results Recurrent Oligo (n=35) had significantly higher PFS (median: 3.1 vs 0.8 years, respectively, P = 0.002) and OS (median: 6.3 vs 1.5 years, respectively, P &lt; 0.001) than Astro (n=59). Overall, 90% of recurrences were local. Eight-three percent received AC as the first-line SST; 50% received salvage surgery before SST; approximately 50% with local failure &gt;2 years after prior RT received reirradiation. On MVA, non-AC was associated with worse OS for both Oligo and Astro; salvage surgery was associated with improved PFS and OS for Astro; early reirradiation was associated with improved PFS for Astro. Conclusions Recurrent radiation-relapsed IDH-mutant gliomas represent a heterogeneous group with variable treatment approaches. Surgery, AC, and reirradiation remain the mainstay of salvage options for retreatment.

scholarly journals The Clinical Implications and Molecular Mechanism of CX3CL1 Expression in Urothelial Bladder Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Guangliang Jiang ◽  
Hui Wang ◽  
Da Huang ◽  
Yishuo Wu ◽  
Weihong Ding ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Cox Regression ◽  
Progression Free Survival ◽  
Mapk Signaling ◽  
High Expression ◽  
Pathway Enrichment Analysis ◽  
Cancer Specific Survival ◽  
Cox Regression Analysis

BackgroundCX3CL1 is a chemokine that may play important roles in cancer immune regulation. Its mechanism in bladder cancer (BCa) is poorly understood. The objective of the current study was to evaluate the association between CX3CL1 and BCa and the related biological mechanisms.MethodsA total of 277 patients with BCa were enrolled in the present study. The association between CX3CL1 expression and disease outcome was evaluated. In vitro and in vivo experiments were performed using the TCCSUP cell line to investigate the function of CX3CL1 in BCa.ResultsCompared with low expression, high expression of CX3CL1 was significantly associated with poorer progression-free survival (hazard ratio [HR]=2.03, 95% confidence interval [95% CI]: 1.26-3.27, P=0.006), cancer-specific survival (HR=2.16, 95% CI: 1.59-2.93, P&lt;0.001), and overall survival (HR=1.55, 95% CI: 1.08-2.24, P=0.039). Multivariable Cox regression analysis suggested that CX3CL1 was an independent prognostic factor for BCa outcomes. In vitro and in vivo experiments indicated that high expression of CX3CL1 was significantly associated with cell proliferation (P&lt;0.001) and invasion (P&lt;0.001). Gene expression profiling results showed that after CX3CL1 knockdown, CDH1 was significantly upregulated, while ETS1, RAF1, and EIF4E were significantly downregulated. Pathway enrichment analysis suggested that the ERK/MAPK signaling pathway was significantly inhibited (P&lt;0.001).ConclusionsCX3CL1 is an independent predictor of a poor prognosis in BCa and can promote the proliferation and invasion of BCa cells.

scholarly journals Blood-based extracellular matrix biomarkers as predictors of survival in patients with metastatic pancreatic ductal adenocarcinoma receiving pegvorhyaluronidase alfa

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Song Wang ◽  
Cecilie L. Bager ◽  
Morten A. Karsdal ◽  
Dimitrios Chondros ◽  
Darin Taverna ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Cox Regression ◽  
Progression Free Survival ◽  
Predictive Biomarker ◽  
Ductal Adenocarcinoma ◽  
Type Iii Collagen ◽  
Ecm Remodeling ◽  
Cox Regression Analysis ◽  
Stage 1

Abstract Background Extensive extracellular matrix (ECM) remodeling is a hallmark of metastatic pancreatic ductal adenocarcinoma (mPDA). We investigated fragments of collagen types III (C3M, PRO-C3), VI (PRO-C6), and VIII (C8-C), and versican (VCANM) in plasma as biomarkers for predicting progression-free survival (PFS) and overall survival (OS) in patients with mPDA treated with pegvorhyaluronidase alfa, a biologic that degrades the ECM component hyaluronan (HA), in a randomized phase 2 study (HALO109-202). Methods HALO109-202 comprised a discovery cohort (Stage 1, n = 94) and a validation cohort (Stage 2, n = 95). Plasma ECM biomarkers were analyzed by ELISAs. Univariate Cox regression analysis and Kaplan–Meier plots evaluated predictive associations between biomarkers, PFS and OS in patients treated with pegvorhyaluronidase alfa plus nab-paclitaxel/gemcitabine (PAG) versus nab-paclitaxel/gemcitabine (AG) alone. Results PFS was improved with PAG vs. AG in Stage 1 patients with high C3M/PRO-C3 ratio (median cut-off): median PFS (mPFS) 8.0 vs. 5.3 months, P = 0.031; HR = 0.40; 95% CI 0.17–0.92). High C3M/PRO-C3 ratio was validated in Stage 2 patients by predicting a PFS benefit of PAG vs. AG (mPFS: 8.8 vs. 3.4 months, P = 0.046; HR = 0.46; 95% CI 0.21–0.98). OS was also improved in patients with high C3M/PRO-C3 ratio treated with PAG vs. AG (mOS 13.8 vs 8.5 months, P = 0.009; HR = 0.35; 95% CI 0.16–0.77). Interestingly, high C3M/PRO-C3 ratio predicted for a PFS benefit to PAG vs. AG both in patients with HA-low tumors (HR = 0.36; 95% CI 0.17–0.79) and HA-high tumors (HR = 0.20; 95% CI 0.06–0.69). Conclusions The C3M/PRO-C3 ratio measuring type III collagen turnover in plasma has potential as a blood-based predictive biomarker in patients with mPDA and provides additional value to a HA biopsy when applied for patient selection. Trial registration: NCT01839487. Registered 25 April 2016

Sign in / Sign up

Export Citation Format

Share Document