Docetaxel Failure Research Articles

No significant impact of prior treatment profile with docetaxel on the efficacy of cabazitaxel in Japanese patients with metastatic castration-resistant prostate cancer

The objective of this study was to retrospectively analyze the oncological outcomes of Japanese patients with metastatic castration-resistant prostate cancer (mCRPC) who received cabazitaxel. This study included a total of 63 consecutive Japanese mCRPC patients treated with cabazitaxel following the failure of docetaxel, and assessed the prognostic significance of cabazitaxel therapy in these patients focusing on the association of efficacies between two taxane agents. After treatment with cabazitaxel (median 5 cycles), prostate-specific antigen (PSA) decline was observed in 39 patients (61.9%), including 13 (27.0%) achieving the response defined by PSA decline ≥50%. The median progression-free survival (PFS) and overall survival (OS) periods after the introduction of cabazitaxel were 4.1 and 14.8months, respectively. The response rate to cabazitaxel was not significantly different between responders and non-responders to prior docetaxel, and there was no significant correlation between the PFSs with docetaxel and cabazitaxel. Furthermore, univariate analyses of several parameters identified the performance status (PS) and clinical symptoms, but not the cycles of docetaxel therapy, total amount of administered docetaxel or objective response to docetaxel therapy, as significant predictors of OS on cabazitaxel therapy, of which only PS was independently associated with OS on multivariate analysis. These findings suggest that oncological outcomes in Japanese mCRPC patients receiving cabazitaxel are generally satisfactory, irrespective of the profiles related to prior treatment with docetaxel, and that it might be preferable to introduce cabazitaxel to mCRPC patients with a good PS to maximize the prognostic benefit of this agent.

Radio-223 en la secuencia terapéutica del cáncer de próstata resistente a la castración metastásico

ContextRadium-223 is an □ -particle transmitter with specific action on bone metastases. The Alpharadin in Symptomatic Prostate Cancer Patients (ALSYMPCA) study showed that radium-223 extended overall survival and delayed the onset of bone events in patients with symptomatic castration-resistant prostate cancer with bone metastases (mCRPC) and without visceral metastases, with a good safety profile. ObjectiveTo review the new scientific evidence on radium-223 based on prespecified and post-hoc analyses of the ALSYMPCA study and on early-access programs after the publication of the ALSYMPCA study, thereby providing new data on the management of patients with mCRPC. Acquisition of evidenceWe searched for evidence on PubMed and in the abstracts of international urology and oncology congresses, as well as ongoing clinical trials (ClinicalTrials.gov). Synthesis of the evidenceThe results of the reviewed studies offer promising results that will broaden the therapeutic benefits of radium-223 to patients with mild symptoms and those with no symptoms. The results also provide preliminary evidence on the benefit of radium-223 treatment after the failure of docetaxel, enzalutamide or abiraterone or the combination of radium-223 with these agents or other therapeutic agents such as bone-targeted agents and immunotherapy. ConclusionRadium-223 can be a treatment option for patients with mild symptoms and can provide a therapeutic benefit after failure of currently available treatments or in combination with these treatments. This evidence should be corroborated in clinical trials before being added to clinical practice.

Metastatic prostate cancer : Update: position paper for the use of chemotherapy

Taxen-based chemotherapy has been established as an effective treatment option in castration-resistant metastatic prostate cancer (mCRPC). Randomized phaseIII studies, however, have shown that even in the hormone-naïve metastatic state, the early use of chemotherapy in addition to the classical androgen deprivation therapy (ADT) approach leads to asignificant increase in median overall survival. This position paper aims to provide current data and orientation in the evidence-based treatment of mPC patients in daily clinical practice. AGerman group of clinical experts analyzed the current data and developed criteria for the treatment of mPC patients in daily clinical practice. In the current treatment of hormone-naïve mPC, abeneficial effect of chemotherapy in addition to ADT has become evident. Provided patients are in an appropriate condition, those with ahigh metastatic load should receive chemotherapy in addition to ADT. Especially in high-risk mCRPC patients (PSA >114 ng/ml, visceral metastasis, ADT response <12months, tumor-associated complaints), first-line chemotherapy is indicated. After docetaxel failure, continuous treatment with cabazitaxel shows superior overall survival compared to sustained antihormonal therapy. Chemotherapy is firmly established in treating patients with mCRPC. Long-term, it will be important to identify molecular predictors. The authors suggest the early use of chemotherapy in hormone-naïve mPC, but note that the approval in this indication is currently nonexistent. After disease progression, patients should be treated analogous to mCRPC.

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.

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 &lt; 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 &gt; 3.1 (log-rank; P &lt; 0.0001). Similarly, the median PFS was 5.5 and 3.8 (log-rank; P &lt; 0.0001) in pts with NLR ≤ 3.66 and &gt; 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.

Cabazitaxel in recurrent/metastatic squamous cell carcinoma of the head and neck: phase II UNICANCER trial ORL03.

Treatments are limited after platinum Cetuximab or anti-PD1 failure for patients with recurrent/metastatic head and neck squamous cell carcinoma. Cabazitaxel has increased overall survival in hormone-refractory metastatic prostate cancer after failure of Docetaxel. Our aim was to detect a signal of activity with Cabazitaxel in patients with head and neck cancer who had failed platinum-, Cetuximab- and taxanes-based chemotherapy.This multicenter phase II trial included progressive patients with an ECOG ≤2. Cabazitaxel was given at 25 mg/m2/3 weeks (maximum of 10 cycles), with growth factors support. Efficacy was centralized and assessed every 6 weeks. The primary endpoint was control rate at six-weeks. A Simon’s two-stage optimal design (P0=0.10; P1=0.30) required 29 evaluable patients. At the end of trial, at least 6 non-progressions were required to consider the drug worthy of further study.Out of the 31 enrolled patients, 29 were eligible; 42% had received at least three previous lines of chemotherapy. For the primary end point, 8 patients (27.6%; 95%CI 12.7%-47.2%) had a stable disease at six weeks. Median progression-free survival was 1.05 months (95%CI 0.69-2.07). All patients were analyzed for toxicity: 6 patients had febrile neutropenia.During the 81 cycles administered, 49 grade 3-5 events were observed concerning 81% of the patients, including 35 severe adverse events of which 15 were related to Cabazitaxel.Although Cabazitaxel met its primary endpoint to deserve further investigations, its toxicity makes it difficult to use in frail patients and new schemes are needed (20 mg/m2 for example) if further investigations are launched.

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.

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 &lt; 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 &gt; 3.1 (log-rank; P &lt; 0.0001). Similarly, the median PFS was 5.5 and 3.8 (log-rank; P &lt; 0.0001) in pts with NLR ≤ 3.66 and &gt; 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.

Patients with metastatic castration-resistant prostate cancer (mCRPC) who are long-term responders (LTR) to the new agent (NA)-based second line: Clinical outcomes and prognostic factors of subsequent treatment with another NA.

254 Background: Three NA [abiraterone acetate (AA), cabazitaxel (CABA), or enzalutamide (ENZ)] are able to significantly prolong their overall survival (OS) after docetaxel failure. A quote of pts can obtain a prolonged disease control over 12 months with a second line NA 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 LTR to a second line NA. Methods: We collected data of pts who received sequentially two NAs after DOC. For each pt we recorded the clinical outcome of treatments received after DOC. We consider as LTR pts without progression over 12 months from the start of the NA second line. We assessed the independent prognostic value of a series of third-line baseline covariates, in terms of progression free survival (PFS) and OS by Cox regression analysis. Results: A consecutive series of 476 mCRPC pts received a NA-based second line: AA (261 pts), CABA (151), and ENZ (64): we identified 116 LTR pts (AA 71 – CABA 28 – ENZ 17). All pts received a subsequent NA-based third line: 27 received AA, 59 CABA, and 30 ENZ. Comparing the third-line outcomes of LTR and no-LTR pts , no statistically significant differences were observed in terms of both biochemical and objective response rate, and PFS, while LTR showed a statistically significant longer OS (median 18 vs 11.4 mos; p&lt; 0.0001). The third line OS was statistically significant different (p = 0.01) according to the sequence adopted (Table). At the multivariate analysis , performance status (PS) and the presence of visceral metastases were independent prognostic factors for PFS in third line, while PSA, PS and lactate dehydrogenase were independent prognostic factors for OS. Conclusions: In our experience, NA-based third line is active also in mCRPC LTR population with highest benefit in sequences with CABA and some factors may help in selecting patients with higher probability of achieving a disease control. [Table: see text]

Patients with metastatic castration-resistant prostate cancer (mCRPC) are primary resistant (PR) to the new agent (NA)-based second line: Clinical outcomes and prognostic factors of subsequent treatment with another NA.

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.

The Influence of Prednisone on the Efficacy of Cabazitaxel in Men with Metastatic Castration-Resistant Prostate Cancer.

Background: Cabazitaxel is a second-generation taxane that is approved for use with concomitant low dose daily prednisone in metastatic castration resistant prostate cancer (mCRPC) after docetaxel failure. Since the role of daily corticosteroids in improving cabazitaxel efficacy or ameliorating its safety profile has not been adequately investigated so far, we compared outcomes of patients receiving cabazitaxel with or without daily corticosteroids in a retrospective single-Institution cohort of mCRPC patients.Patients and methods: Medical records of deceased patients with documented mCRPC treated with cabazitaxel following prior docetaxel between January, 2011 and January, 2017 were reviewed at the single participating center. Patients who were receiving daily doses of systemic corticosteroids other than low dose daily prednisone or prednisolone (<= 10 mg a day) were excluded. The primary end point of this analysis was overall survival (OS). Secondary end-points were exposure to cabazitaxel as well as incidence of grade 3-4 adverse events. Univariable and multivariable Cox proportional hazards regression was used to evaluate prednisone use and other variables as potentially prognostic for overall survival.Results: Overall, among 91 patients, 57 patients received cabazitaxel concurrently with low dose prednisone and 34 patients did not receive concurrent prednisone. The median overall survival of the population was 9.8 months (interquartile range, 9 to 14). Patients receiving prednisone had an overall survival of 9 months (interquartile range, 8 to 12) vs.14 months (interquartile range, 9.4 to 16.7) for patients not treated with prednisone. Approximately 45% of patients had a >30% PSA decline at 12 weeks. Prednisone use was not significantly prognostic for overall survival or PSA decline ≥30% rates on regression analyses. Importantly, a >30% PSA decline at 12, but not at 3, 6, 9 weeks, was prognostic for improved survival at multivariate analysisConclusions: The data presented here support the hypothesis that omitting daily corticosteroids in cabazitaxel-treated patients has no negative impact on either survival or safety profile. In the large prospective trial CABACARE, cabazitaxel-treated patients will be randomized to receive or not receive daily prednisone. The CABACARE (EudraCT n. 2016-003646-81) study is currently ongoing at University Federico II of Naples and at other multiple participating centers in Italy.

An exploratory analysis of the association between levels of hormones implied in steroid biosynthesis and activity of abiraterone in patients with metastatic castration-resistant prostate cancer.

Abiraterone acetate, approved for patients with metastatic castration-resistant prostate cancer (mCRPC), blocks androgen byosinthesis. We aimed to describe changes determined by abiraterone in hormones implied in steroid biosynthesis, exploring association between hormonal levels and drug activity. Patients with mCRPC, receiving standard abiraterone + prednisone after docetaxel failure, were studied. We determined serum levels of progesterone, 17OH-progesterone, cortisol, ACTH, DHEA-sulphate, androstenedione, testosterone, sex hormone-binding globulin, aldosterone, plasma renin activity, and cholesterol, baseline and every 12 weeks. For each hormone, association with treatment activity was tested 1) comparing baseline values in responders vs. non-responders; 2) comparing progression-free survival (PFS) of patients with baseline low vs. high values; 3) comparing values after 12 weeks in responders vs. non-responders. Forty-nine patients were analyzed; 26 patients (53.1%) experienced PSA response. Baseline values of all hormones were not statistically different between responders and non-responders. For all hormones, PFS difference of patients with low vs. high baseline values was not statistically significant. Several hormones showed significant and sustained changes vs. baseline, but all significant changes were similar between responders and non-responders. This analysis does not suggest a significant association between baseline hormonal values, or changes induced by abiraterone, and treatment activity.

Abiraterone acetate for metastatic castration‐resistant prostate cancer after docetaxel failure: A randomized, double‐blind, placebo‐controlled phase 3 bridging study

To evaluate the efficacy and safety of abiraterone acetate-prednisone versus placebo-prednisone in Asian metastatic castration-resistant prostate cancer patients who have failed docetaxel-based chemotherapy. In this double-blind, phase 3 study from China, 214 patients were randomized (2:1) to abiraterone acetate 1000 mg once daily plus prednisone 5 mg twice daily and placebo plus prednisone 5 mg twice daily in 28-day treatment cycles. Abiraterone acetate-prednisone treatment significantly decreased prostate-specific antigen progression risk by 49%, with longer median time to prostate-specific antigen progression of 5.55 months versus 2.76 months in the placebo-prednisone group (hazard ratio 0.506, P = 0.0001, primary end-point). There was a strong trend for improved overall survival in the abiraterone acetate-prednisone group, with a 40% decrease in the risk of death (hazard ratio 0.604, P = 0.0597); however, median survival was not reached in either group because of the short follow-up period (12.9 months) and limited number of observed death events. The prostate-specific antigen response rate was higher in the abiraterone-prednisone group (49.7%) than in the placebo-prednisone group (14.1%). A total of 37.1% patients in this group had pain progression events compared with 50.7% in the placebo-prednisone group. Abiraterone-prednisone significantly decreased the risk of pain progression by 50% (hazard ratio 0.496, P = 0.0014). The incidence of adverse events was similar between the two groups; the most common adverse events being anemia (25.9% for abiraterone-prednisone vs 22.5% for placebo-prednisone), hypokalemia (25.9% and 11.3%), bone pain (23.8% and 21.1%), hypertension (16.1% and 12.7%) and increased aspartate aminotransferase (14.7% and 15.5%), respectively. Abiraterone-prednisone significantly delays disease and pain progression, and prostate-specific antigen, with a favorable benefit-risk ratio in Asian metastatic castration-resistant prostate cancer patients in the post-docetaxel setting.

Is metronomic cyclophosphamide (mCTX) a therapeutic option for metastatic castration-resistant prostate cancer (mCRPC) patients (pts) in the era of new agents (NAs)? A retrospective multicenter Italian study.

326 Background: Several NAs, such as abiraterone acetate (AA), cabazitaxel (CABA), and enzalutamide (ENZ), are able to significantly prolong mCRPC pts survival after docetaxel (DOC) failure. Nevertheless, all pts eventually show progressive disease with NAs and several pts may require further treatment. mCTX was considered as a feasible and tolerable therapeutic option after DOC failure before the introduction of NAs in the clinical practice. The present retrospective study describes the clinical outcomes of mCTX, used in mCRPC pts after the failure of both DOC and at least one NA. Methods: We retrospectively reviewed the clinical records of all mCRPC pts treated in 8 Italian hospitals after the introduction of NAs in the clinical practice. We considered as eligible for the present analysis all pts who received mCTX after DOC and at least one NA. All pts were treated with CTX 50 mg po daily until disease progression. Results: From December 2011 to June 2015, a consecutive series of 48 mCRPC pts, median age 72 yrs (56-90), with bone (94%), nodal (67%) or visceral (25%) mets, was treated with mCTX. All pts have previously received a DOC-based chemotherapy followed by only one NA in 21 cases, two NAs in 20, and all three NAs in 7. The median duration of the treatment was 10.4 wks (range 3.6-61.1). Recorded grade 3-4 toxicities were: anemia (5 pts), leucopenia (1), thrombocytopenia (2), fatigue (2), and anorexia (1). Seven pts (14%) achieved a PSA reduction ≥ 50% and 2 (4%) an objective response. The median progression free survival (PFS) was 3.5 mos with 7 pts (14%) showing a PFS ≥ 9 mos. The median overall survival was 6.9 mos. Conclusions: In our experience, mCTX was a feasible and well tolerated therapeutic option in heavily pre-treated pts with very advanced mCRPC. Despite its activity was limited, the clinical outcomes of this cheap treatment are similar to those observed with NAs administered in third/fourth line with a quote of pts experiencing a prolonged disease control. Prospective studies are needed to define the therapeutic role of mCTX after NAs in mCRPC pts.

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: Preliminary results from a multicenter Italian study.

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 &lt; 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 &gt; 3.1 (log-rank; P &lt; 0.0001). Similarly, the median PFS was 6.3 and 3.5 in pts with NLR ≤ 3.1 and &gt; 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.

Long-term outcomes and predictive factors in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) showing abiraterone withdrawal syndrome (AWS) after docetaxel (DOC) treatment.

324 Background: AWS has been rarely described as a possible PSA reduction, with or without radiological responses, observed after abiraterone acetate (AA) suspension due to disease progression. According to this possibility, all pts progressing under AA were usually monitored for at least 4 wks to evaluate if they developed AWS; if PSA decreased, the subsequent treatment was delayed until the occurrence of biochemical and/or radiological progression. The present study is aimed to assess long-term outcomes and predictive factors in DOC pre-treated mCRPC pts experiencing AWS. Methods: We evaluated a consecutive series of 73 pre-treated mCRPC pts, who received AA in our Hospital after DOC failure: all pts were treated with AA 1,000 mg po + prednisone 10 mg po daily; the treatment continued until progression disease (PD) which required to be confirmed by imaging. For each pt we have recorded the pre and post-AA clinical history, the treatment details and outcomes. All pts stopped AA due to progressive disease and AWS was defined by PSA reduction ≥ 25%, compared to the AA-end values, observed in the first month after AA stop. A logistic regression analysis was performed in order to assess the ability of a series of 18 selected clinical factors to predict AWS. Results: AWS was observed in 7 pts (9.5%) with a median duration of 17 wks (range 9-33). Two pts undergoing the 3-monthly radiographic restaging showed an objective response. A significant difference in terms of post-AA median OS was observed between AWS- and AWS+ pts (3.6 vs 27.9 mos; p = 0.02); this differences was confirmed by 1-month landmark analysis (4.6 vs 27.9 mos; p = 0.03). Among the factors, only the absence of pain at AA therapy baseline was able to predict the AWS: 100% of AWS+ pts were asymptomatic, compared to 64.6% of AWS- pts (p = 0.04). Conclusions: Despite AWS remains an unpredictable and rare phenomenon, it could represent a chance to delay the start of subsequent therapeutic line after AA failure. Moreover, our results seem to suggest that the occurrence of AWS may have a positive impact on the OS of mCRPC pts.

F26 - Prognostic and predictive role of 18F-choline (c) positron emission tomography (PET) in patients (pts) with metastatic castration resistant prostate cancer (mCRPC) treated with enzalutamide (ENZ) after docetaxel (DOC) failure

F26 - Prognostic and predictive role of 18F-choline (c) positron emission tomography (PET) in patients (pts) with metastatic castration resistant prostate cancer (mCRPC) treated with enzalutamide (ENZ) after docetaxel (DOC) failure

Metabolic syndrome in castration-resistant prostate cancer patients treated with abiraterone.

Metabolic syndrome (MS) has not yet been studied in castration-resistant prostate cancer (CRPC) men treated with novel hormonal therapies. The study aims to assess the impact of MS on outcome from time starting abiraterone. We retrospectively evaluated a consecutive series of metastatic CRPC patients treated with abiraterone after docetaxel failure. MS, as defined by modified Adult Treatment Panel (ATP) III criteria, was assessed at the time of initiation of abiraterone, during treatment and follow-up. Sixty-seven of 178 patients evaluated (37.6%) met MS criteria at baseline, before abiraterone initiation, whereas for 11 (9.9%) without MS before treatment with abiraterone this occurred during treatment. Median PFS was equal to 4.7 months for patients with MS versus 9 months for those without MS. Patients with MS had an increased risk of 71% of progression or death for all causes than patients without MS (HR = 1.7, 95% CI [1.2-2.4], P = 0.03). Median OS was 14.7 months and 22.3 months in patients with and without MS, respectively. After adjusting for covariates, MS resulted not significantly associated to OS (HR = 1.42, 95% CI [0.91-2.22], P = 0.073). The presence of MS is a significant risk factor for shorter PFS in CRPC patients treated with abiraterone, even if it does not show a significant impact on OS. A prospective evaluation is warranted.

Multivariable analysis of predictors of side effects of cabazitaxel in the Italian Expanded Access Program.

225 Background: Cabazitaxel-based chemotherapy provides a survival benefit after docetaxel failure in patients with prostate cancer. Grade 3-4 neutropenia and febrile neutropenia were relatively frequent in the registrative trial, but their incidence in clinical practice is likely to be lower, as shown by data collected in the Expanded Access Program (EAP). While cumulative doses of docetaxel are associated to neuropathy, the effect of cumulative doses of cabazitaxel is unknown. In this study, we assessed 'per cycle' incidence and predictors of toxicity in the Italian cohort of the EAP, with a focus on the effect of cumulative doses of cabazitaxel. Methods: The study population consisted of 218 Italian patients enrolled in the cabazitaxel EAP. The influence of selected variables on the most relevant side effects identified was assessed using a Generalised Estimating Equations (GEE) model at univariate and multivariate analysis. Multivariate logistic regression analysis was performed using a backward selection procedure. Variables with a p value ⩽0.1 were kept in the final model. Results: Per cycle incidence of grade 3-4 neutropenia was 8.7%, while febrile neutropenia occurred only in 0.9% of cycles and was an early event, occurring during the first three cycles only. Multivariate logistic regression analysis showed that the odds of having grade 3 – 4 neutropenia, febrile neutropenia and anemia were statistically significantly reduced by 10, 48 and 7%, respectively, every 10 mg/m2 increase of total prior dose of cabazitaxel. Interestingly, a body surface area &gt; 2 m2 was associated to increased odds of having grade 3-4 neutropenia. In this regard, it must be noted that all patients with body surface area &gt; 2 m2 had their total dose capped to 50 mg, with a mean (95% CI) and median (IQR) dose reduction of 7.1 (7.58-6.69) and 5.9 (2.76-10.27) % with respect to planned dose. Conclusions: Cumulative doses of cabazitaxel are associated to decreased risk of bone marrow toxicity. Patients with body surface area &gt;2 m2 are at increased risk of bone marrow toxicity and dose capping should be considered. These data indicate that cabazitaxel should not be arbitrarily suspended because of concerns of cumulative toxicity.

Metabolic syndrome in castration-resistant prostate cancer patients treated with abiraterone.

213 Background: The presence and the impact of metabolic syndrome (MS) in castration-resistant prostate cancer (CRPC) men treated with novel hormonal therapies, as abiraterone, has not still been studied. The study aims to assess the impact of MS on progression free survival (PFS) and overall survival (OS) from time starting abiraterone. Methods: We retrospectively evaluated a consecutive series of metastatic CRPC patients treated with abiraterone after docetaxel failure. MS, as defined by modified Adult Treatment Panel (ATP) III criteria, was assessed at the time of initiation of abiraterone, during treatment and follow-up. Cox regression model was used to evaluate the role of MS on the two end-points. Results: One hundred seventy eight patients had sufficient data to assess the presence of MS. Mean age (± SD) at start of abiraterone was 74.0 ± 7.7 years. Seventy out of 178 patients (39.5%) met MS criteria at baseline, before abiraterone initiation, whereas for eleven patients this occurred during treatment. Median PFS was equal to 5 months for patients with MS versus 9 months for those without MS. Patients with MS had a 2-fold increased risk of progression or death for all causes than patients without MS (HR=1.9, 95% CI [1.3-2.7], P&lt;0.001). Median OS was 16 months and 22 months in patients with and without MS, respectively. After adjusting for covariates, MS resulted not significantly associated to OS (HR=1.2, 95% CI [0.8-1.9], P=0.340). Conclusions: MS may represent a complication of patients treated with abiraterone. The presence of MS appears to be a risk factor for shorter PFS in patients with CRPC treated with abiraterone, even if it does not show any impact on OS, so it needs a further prospective evaluation.

Primary resistance to abiraterone acetate (AA) after docetaxel treatment in metastatic castration-resistant prostate cancer (mCRPC): A multicenter retrospective analysis.

206 Background: AA improves survival in mCRPC patients pre-treated with docetaxel. All patients eventually become resistant at different interval times, but some of them show an early progression and should be considered as primary resistant (PRES). To date, no factors have been identified as predictive of primary resistance. Methods: The clinical outcomes of a consecutive series of patients treated with AA after docetaxel failure in 19 Italian Hospitals within a Named Patient Program (NPP) was previously reported (BJU 2014). In the present analysis, we focus on patients who achieved an investigator-assessed PFS ≤ 3 months (PRES) and those with PFS ≥ 12 months (long term responders, LR). The main aim is to determine clinical characteristics associated with primary resistance. Results: Among the 265 patients enrolled in the NPP, we identified 97 PRES (37%) and 71 LP (27%). Poor performance status, visceral metastases, presence of pain, low baseline haemoglobin level, increased LDH and ALP levels, and short time from diagnosis to AA therapy were significantly associated with early progression (Table). Conclusions: Several clinical parameters appear to correlate with early progression under AA. Their role as potential predictive factors of resistance deserve further exploration in order to develop alternative treatment strategies. [Table: see text]

P072 Activity and clinical outcomes of New Agents (NAs) administered as third or fourth line after the failure of docetaxel (DOC) and another NA in metastatic Castration-Resistant Prostate Cancer (mCRPC) patients. Final results of an Italian multicentre retrospective study

P072 Activity and clinical outcomes of New Agents (NAs) administered as third or fourth line after the failure of docetaxel (DOC) and another NA in metastatic Castration-Resistant Prostate Cancer (mCRPC) patients. Final results of an Italian multicentre retrospective study