Keita Tamura

Comparative Assessment of Efficacies Between 2 Alternative Therapeutic Sequences With Novel Androgen Receptor-Axis-Targeted Agents in Patients With Chemotherapy-Naïve Metastatic Castration-Resistant Prostate Cancer

Background The objective of this study was to compare the efficacies of sequential therapies with novel androgen receptor‐axis‐targeted (ARAT) agents in patients with docetaxel‐naïve metastatic castration‐resistant prostate cancer (mCRPC). Patients and Methods This study included 108 consecutive patients with mCRPC who sequentially received abiraterone acetate (AA) and enzalutamide (Enz), in either order, without prior treatment with docetaxel. The combined prostate‐specific antigen (PSA) progression‐free survival (PFS) was defined as the sum of PFS1 and PFS2, representing PSA PFSs on the first and second ARAT agents, respectively. Results Of these patients, 49 and 59 received ARAT therapy with the AA‐to‐Enz sequence (AA‐to‐Enz group) and with the reverse sequence (Enz‐to‐AA group), respectively. No significant differences in the baseline characteristics were noted between the 2 groups. In the overall patient population, the PSA response rate to the second‐line ARAT agent (21.3%) was significantly lower than that of the first‐line ARAT agent (58.3%). The combined PSA PFS in the AA‐to‐Enz group (median, 18.4 months) was significantly superior to that of the Enz‐to‐AA group (median, 12.8 months). Furthermore, multivariate analysis identified the treatment sequence (ie, AA‐to‐Enz vs. Enz‐to‐AA group) in addition to performance status as an independent predictor of combined PSA PFS in these patients. However, there was no significant difference in overall survival (OS) between the 2 groups. Conclusions Although cross‐resistance between ARAT agents is a common phenomenon in docetaxel‐naïve patients with mCRPC, different efficacies were observed favoring the AA‐to‐Enz rather than Enz‐to‐AA sequence in this series with respect to combined PSA PFS but not OS. Micro‐Abstract The investigation of the efficacy of sequential therapies with novel androgen receptor‐axis‐targeted (ARAT) agents for docetaxel‐naïve patients with metastatic castration‐resistant prostate cancer revealed the superiority of the abiraterone‐to‐enzalutamide sequence over the reverse sequence regarding combined prostate‐specific antigen progression‐free survival, but not overall survival. Therefore, despite the occurrence of cross‐resistance with either sequence, ARAT therapy with the abiraterone‐to‐enzalutamide sequence might be preferable.

Comparison of Alternative Androgen Receptor-axis-targeted Agent (ARATA) and Docetaxel as Second-line Therapy for Patients With Metastatic Castration-resistant Prostate Cancer With Progression After Initial ARATA in Real-world Clinical Practice in Japan

&NA; The present study included 222 patients with metastatic castration‐resistant prostate cancer. Of the 222 patients, 108 and 114 received an alternative androgen receptor‐axis‐targeted agent (ARATA) or docetaxel, respectively, after the failure of initial ARATA. We found that the oncologic outcomes, including the response rate, progression‐free survival, and overall survival, were significantly superior in the 114 patients receiving docetaxel compared with those of the 108 patients receiving ARATA. Background: The objective of the present study was to assess the oncologic outcomes of patients receiving second‐line therapy against metastatic castration‐resistant prostate cancer (mCRPC). Patients and Methods: The present study included 222 consecutive mCRPC patients with progression during initial androgen receptor‐axis‐targeted agent (ARATA) therapy with either abiraterone acetate (AA) or enzalutamide (Enz). Of these 222 patients, 108 subsequently received an alternative ARATA (AA‐to‐Enz, n = 49; Enz‐to‐AA, n = 59) and 114 received docetaxel (DTX; AA‐to‐DTX, n = 54; Enz‐to‐DTX, n = 60). Results: The prostate‐specific antigen (PSA) level in the 114 patients receiving DTX was significantly greater than that in the 108 patients receiving ARATA. However, no significant differences were found in the remaining parameters between the 2 groups. The PSA response rate, PSA progression‐free survival (PFS), and overall survival (OS) during second‐line therapy in the DTX group (n = 114) were significantly superior to those for the ARATA group (n = 108; PSA response rate, 42.1% vs. 21.3%; median PSA PFS, 7.2 vs. 4.2 months; median OS, 17.5 vs. 14.5 months). Similar trends were confirmed by comparing these outcomes among 4 therapy groups, with significant differences (PSA response rate, Enz‐to‐AA vs. AA‐to‐DTX and Enz‐to‐AA vs. Enz‐to‐DTX; PSA PFS, AA‐to‐Enz vs. Enz‐to‐AA, AA‐to‐Enz vs. AA‐to‐DTX, Enz‐to‐AA vs. AA‐to‐DTX, and Enz‐to‐AA vs. Enz‐to‐DTX; and OS, Enz‐to‐AA vs. AA‐to‐DTX and Enz‐to‐AA vs. Enz‐to‐DTX). Furthermore, the introduction of DTX was independently associated with improved PSA PFS, but not OS, on multivariate analysis. Conclusion: Favorable oncologic outcomes can be expected with DTX treatment, rather than with alternative ARATA, for mCRPC patients after failure of an initial ARATA.

PD10-12 NO SIGNIFICANT IMPACT OF RESPONSE TO PRIOR ANDROGEN RECEPTOR-AXIS-TARGETED AGENTS ON THE EFFICACY OF SUBSEQUENT DOCETAXEL IN PATIENTS WITH METASTATIC CASTRATION-RESISTANT PROSTATE CANCER

Background To investigate whether the response to an androgen receptor-axis-targeted (ARAT) agent is associated with the efficacy of subsequent docetaxel in metastatic castration-resistant prostate cancer (mCRPC) patients.

Clinical characteristics of self-reported nocturia in patients with interstitial cystitis, and effects of bladder hydrodistention (with fulguration of Hunner lesions) on nocturia

The aim of this study was to investigate the clinical characteristics of nocturia in patients with interstitial cystitis (IC), and the effects of bladder hydrodistention (with fulguration of Hunner lesions) on nocturia.

Significance of De Ritis (Aspartate Transaminase/Alanine Transaminase) Ratio as a Significant Prognostic But Not Predictive Biomarker in Japanese Patients with Metastatic Castration-resistant Prostate Cancer Treated with Cabazitaxel

Background/Aim: To date, there have not been any established biomarkers predicting the efficacy of cabazitaxel in patients with metastatic castration-resistant prostate cancer (mCRPC). The objective of this study was to evaluate the significance of the aspartate aminotransaminase (AST)/alanine aminotransaminase (ALT) ratio (De Ritis ratio) as a biomarker for mCRPC patients receiving cabazitaxel. Patients and Methods: This study included 74 consecutive docetaxel-refractory mCRPC patients treated with cabazitaxel. It assessed the impact of the pretreatment De Ritis ratio, in addition to conventional clinicopathological parameters, on the oncological outcomes in these patients. Results: After treatment with cabazitaxel, 22 (29.7%) of the 74 patients achieved a prostate-specific antigen (PSA) response; however, there was no significant difference in the PSA response rate between patients with a low De Ritis ratio (<1.35) and those with a high ratio (≥1.35). In this series, the median periods of PSA progression-free survival (PFS) and overall survival (OS) after the introduction of cabazitaxel were 4.2 and 14.7 months, respectively. No significant difference was noted in PSA PFS between the low and high De Ritis ratio groups, whereas OS in the high De Ritis ratio group was significantly poorer compared with that in the low De Ritis ratio group. Univariate analysis showed the significant impact of the De Ritis ratio on OS, but not PFS, in these 74 patients. Furthermore, the De Ritis ratio, in addition to the performance status and lactate dehydrogenase level, was shown to be independently associated with OS on multivariate analysis. Conclusion: Assessment of the De Ritis ratio may provide useful prognostic, but not predictive, information on cabazitaxel therapy in mCRPC patients.

Significance of Age in Japanese Patients Receiving Sunitinib as First-line Systemic Therapy for Metastatic Renal Cell Carcinoma: Comparative Assessment of Efficacy and Safety between Patients Aged <75 and ≥75 Years

Background/Aim: To date, it has not been well characterized whether sunitinib is effective in elderly patients with metastatic renal cell carcinoma (mRCC). The objective of this study was to investigate the impact of age on clinical outcomes of mRCC patients receiving sunitinib. Patients and Methods: The efficacy and safety of first-line sunitinib in 154 consecutive mRCC patients were retrospectively compared between patients aged <75 (n=125) and ≥75 (n=29) years. Results: There were no significant differences in the major clinicopathological characteristics between younger and older patients; however, the reduction of the initial dose of sunitinib was significantly more frequent in older than younger patients. No significant difference in response rate, clinical benefit rate or proportion of patients going on to receive second-line therapy was noted between these two groups. Furthermore, there was no significant difference in progression-free survival (PFS) or overall survival (OS) between the two groups, and no significant impact of age on PFS or OS was documented by the Cox proportional hazards regression analyses. Of several adverse events, only anemia and fatigue were significantly more frequently observed in older than younger patients. Although there was no significant difference in the incidence of dose reduction or discontinuation of sunitinib between the two groups, the interruption of sunitinib was more frequently required in older than younger patients. Conclusion: These findings suggest that advanced age alone should not be regarded as a contraindication to the introduction of sunitinib as first-line systemic therapy for mRCC patients.

Independent association between time to prostate-specific antigen (PSA) nadir and PSA progression-free survival in patients with docetaxel-naïve, metastatic castration-resistant prostate cancer receiving abiraterone acetate, but not enzalutamide

PURPOSE The objective of this study was to compare the prognostic effect of time to prostate-specific antigen (PSA) nadir (TTPN) after treatment with abiraterone acetate (AA) and enzalutamide (Enz) in patients with docetaxel-naïve, metastatic castration-resistant prostate cancer (mCRPC). METHODS This study included a total of 297 consecutive patients with mCRPC, of whom 125 and 172 received AA and Enz, respectively, without previous treatment with docetaxel and subsequently achieved any degree of PSA reduction after the administration of either agent. RESULTS The mean values of TTPN in the AA and Enz groups were 19 and 14 weeks, respectively. Despite the lack of significant differences in several parameters according to the mean TTPN in the Enz group, patients with TTPN>19 weeks were characterized by longer duration of androgen deprivation therapy, better performance status, lower incidence of bone metastasis, lower value of nadir PSA, and higher incidence of PSA response than those with TTPN ≤19 weeks in the AA group. The PSA progression-free survival (PFS) in patients with TTPN >19 weeks was significantly superior when compared with TTPN ≤19 weeks in the AA group; however, there was no significant effect of the mean TTPN on the PSA-PFS in the Enz group. Furthermore, TTPN was identified as one of the independent predictors of PSA-PFS in the AA group but not in Enz group. CONCLUSIONS A longer time to reach a PSA nadir after treatment with AA, but not Enz, appeared to be associated with favorable disease control in patients with docetaxel-naïve mCRPC.

MP16-05 EARLY TUMOR SHRINKAGE UNDER SECOND-LINE TARGETED THERAPY FOR METASTATIC RENAL CELL CARCINOMA AS A PREDICTOR OF OVERALL SURVIVAL: A RETROSPECTIVE MULTIINSTITUTIONAL STUDY IN JAPAN

INTRODUCTION AND OBJECTIVES: It remains the standard approach for assessing the prognosis of mRCC patients treated with molecular-targeted agents to use the MSKCC and IMDC risk classifications, while the significant prognostic impact of the objective tumor response to these novel agents in mRCC patients has recently been documented in various studies. We also reported that the overall survival (OS) in patients with mRCC was closely correlated with the degree of tumor shrinkage at 12 weeks after the introduction of first-line targeted agents (Target Oncol 2016; 11: 175-82). Of these, however, there was no study focusing on data from mRCC patients treated with second-line targeted agents outside clinical trials. The objective of this study was to evaluate the impact of early tumor shrinkage (ETS) induced by a second-line targeted agent on OS in mRCC patients. METHODS: This study retrospectively included 271 consecutive Japanese patients with mRCC who received second-line targeted therapy for at least 3 months. ETS was defined as the degree of tumor shrinkage at the first post-baseline radiological evaluation conducted 4 to 8 weeks after initiating second-line targeted therapy. RESULTS: Of the 271 patients, 26 had ETS from -100 to -50%, 70 from -49 to -25%, 84 from -24 to 0%, and the remaining 91 failed to achieve a reduction in the tumor size. The median OS following the initiation of second-line targeted therapy stratified according to ETS was 45.8, 30.9, 22.1 and 14.2 months, respectively. Univariate analysis identified prior nephrectomy, the MSKCC risk classification, C-reactive protein (CRP) level, number of metastatic organs, sarcomatoid feature, introduced second-line agent and ETS induced by a second-line agent as parameters significantly associated with OS, of which, only the MSKCC classification, CRP level and ETS appeared to have independent impacts on OS on multivariate analysis. CONCLUSIONS: Collectively, these findings suggest that ETS at the first post-baseline assessment under treatment with a second-line targeted agent could serve as a useful parameter with an independent impact on OS in mRCC patients receiving second-line targeted therapy; therefore, it is highly recommended to select second-line targeted agents that make it possible to induce prompt tumor remission to further improve the prognosis of patients with mRCC following the failure of first-line targeted therapy.