Zoledronic acid combined with androgendeprivation therapy may prolong time to castration-resistant prostate cancer in hormone-naı¨ve metastatic prostate cancer patients e A propensity scoring approach

Objective:To clarify the oncological benefit of zoledronic acid for hormone-naive metastatic prostate cancer,patient outcome of androgen deprivation therapy with zoledronic acid(ADT+Z)and androgen deprivation therapy alone(ADT)was compared.Methods:Fifty-two patients with pathologically confirmed metastatic prostate cancer were prospectively enrolled and treated with combined androgen blockade(goserelin and bicalutamide)with zoledronic acid(4 mg every 4 weeks for 24 months).A propensity score-match with logistic regression analysis was applied to select 50 pair-matched cohorts(both from ADT+Z and from historical control cohorts who had undergone ADT alone),and patient outcomes were compared.Results:Patients with ADT+Z had significantly longer time to progression(TTP)than those with ADT(median TTP;24.2 vs.14.0 months,p=0.0092),while no significant difference of overall survival between two groups(p=0.1502).Multivariate analysis for biochemical recurrence revealed treatment with ADT was the sole independent prognostic factor(HR:1.724,95%CI:1.06-2.86,p=0.0297).Conclusion:Combination of zoledronic acid with ADT may prolong time to castration resistant prostate cancer.

Efficacy and Safety of Axitinib as First-Line Therapy in Japanese Patients with Metastatic Renal Cell Carcinoma

Previous study reported that patients treated with axitinib as second-line therapy had longer median progression-free survival than those treated with sorafenib for metastatic renal cell carcinoma (mRCC). In this study, we reviewed our experience of axitinib as a first-line therapy for mRCC in Japanese patients, focusing on its efficacy and safety. We retrospectively assessed 26 patients treated with axitinib as a first-line therapy for mRCC from July 2010 to July 2014 at Chiba Cancer Center and Kinki University Hospital. Observation period was 24.6 ± 18.3 months. The objective response rate was 50.0%, and the median progression-free survival was 27.5 months. Overall survival was not estimable. Common grade 3 adverse events were hypertension in 19 patients and proteinuria in 5 patients. Axitinib demonstrated significant efficacy as a first-line therapy in Japanese patients with mRCC. Careful monitoring and management of the adverse effects may help to control its toxicities.

Apalutamide for metastatic castration-sensitive prostate cancer:final analysis of the Asian subpopulation in the TITAN trial

The final analysis of the phase 3 Targeted Investigational Treatment Analysis of Novel Anti-androgen(TITAN)trial showed improvement in overall survival(OS)and other efficacy endpoints with apalutamide plus androgen deprivation therapy(ADT)versus ADT alone in patients with metastatic castration-sensitive prostate cancer(mCSPC).As ethnicity and regional differences may affect treatment outcomes in advanced prostate cancer,a post hoc final analysis was conducted to assess the efficacy and safety of apalutamide in the Asian subpopulation.Event-driven endpoints were OS,and time from randomization to initiation of castration resistance,prostate-specific antigen(PSA)progression,and second progression-free survival(PFS2)on first subsequent therapy or death.Efficacy endpoints were assessed using the Kaplan–Meier method and Cox proportional-hazards models without formal statistical testing and adjustment for multiplicity.Participating Asian patients received once-daily apalutamide 240 mg(n=111)or placebo(n=110)plus ADT.After a median follow-up of 42.5 months and despite crossover of 47 placebo recipients to open-label apalutamide,apalutamide reduced the risk of death by 32%(hazard ratio[HR]:0.68;95%confidence interval[CI]:0.42–1.13),risk of castration resistance by 69%(HR:0.31;95%CI:0.21–0.46),PSA progression by 79%(HR:0.21;95%CI:0.13–0.35)and PFS2 by 24%(HR:0.76;95%CI:0.44–1.29)relative to placebo.The outcomes were comparable between subgroups with low-and high-volume disease at baseline.No new safety issues were identified.Apalutamide provides valuable clinical benefits to Asian patients with mCSPC,with an efficacy and safety profile consistent with that in the overall patient population.

Consensus on safety management of novel hormonal therapy for advanced prostate cancer

Prostate cancer(PCa)is one of the most prevalent malignant tumors in men,accompanied by high incidence and mortality rates.Novel hormonal therapy(NHT)has emerged as the primary treatment for advanced PCa,providing noticeable clinical benefits.However,the diverse range of adverse events(AEs)associated with NHT may influence both treatment efficacy and patients'quality of life.In light of the latest international clinical research evidence and recommendations from domestic and foreign guidelines,this consensus aims to provide a comprehensive overview of the common AEs experienced during NHT for advanced PCa patients.Additionally,it seeks to develop a hierarchical approach to more efficiently manage AEs,presenting valuable insights for clinical medication and adverse reaction management.

Apalutamide for patients with metastatic castrationsensitive prostate cancer in East Asia:a subgroup analysis of the TITAN trial

Ethnicity might be associated with treatment outcomes in advanced prostate cancer.This study aimed to evaluate the efficacy and safety of androgen deprivation therapy(ADT)combined with apalutamide in East Asians with metastatic castration-sensitive prostate cancer(mCSPC).The original phase 3 Targeted Investigational Treatment Analysis of Novel Anti-androgen(TITAN)trial was conducted at 260 sites in 23 countries.This subgroup analysis included patients enrolled in 62 participating centers in China,Japan,and Korea.Radiographic progression-free survival(PFS),time to prostate-specific antigen(PSA)progression,and PSA changes from baseline were compared between groups in the East Asian population.The intent-to-treat East Asian population included 111 and 110 participants in the apalutamide and placebo groups,respectively.The 24-month radiographic PFS rates were 76.1%and 52.3%in the apalutamide and placebo groups,respectively(apalutamide vs placebo:hazard ratio[HR]=0.506;95%confidence interval[CI],0.302–0.849;P=0.009).Median time to PSA progression was more favorable with apalutamide than placebo(HR=0.210;95%CI,0.124–0.357;P<0.001).Median maximum percentages of PSA decline from baseline were 99.0%and 73.9%in the apalutamide and placebo groups,respectively.The most common adverse event(AE)was rash in the apalutamide group,with a higher rate than that in the placebo group(37.3%vs 9.1%).The most common grade 3 or 4 AEs were rash(12[10.9%])and hypertension(12[10.9%])for apalutamide.The efficacy and safety of apalutamide in the East Asian subgroup of the TITAN trial are consistent with the global results.