Impact of intensified androgen blockade in patients with high-risk biochemically relapsed castration-sensitive prostate cancer

A recent study showed that intensified AR blockade for a finite period extends prostate-specific antigen progression-free survival (PSA-PFS) while maintaining a manageable safety profile, without negatively impacting the time needed for testosterone recovery. This study’s findings were published in the Journal of clinical oncology.

The PRESTO trial was a randomized, open-label, phase III study that involved 503 patients diagnosed with biochemically recurrent prostate cancer (BRPC) and PSA doubling time of 9 months or less. Patients were randomly divided into one of three groups in a 1:1:1 ratio. These groups consisted of a 52-week treatment course with ADT (androgen-deprivation therapy) control, ADT combined with apalutamide, or ADT combined with apalutamide and AAP (abiraterone acetate plus prednisone). The primary endpoint of the trial was to evaluate PSA-PFS, which was defined as having a serum PSA level exceeding 0.2 ng/mL after the completion of the assigned treatment.

The median PSA level was determined to be 1.8 ng/mL (IQR, 1.0-3.6). During the initial planned interim analysis, it was observed that both experimental groups exhibited a significant prolongation in PSA-PFS when compared to the control group (median, ADT + apalutamide was 24.9 months vs 20.3 months for ADT alone; median, ADT + apalutamide + AAP was 26.0 months vs 20.0 months for ADT alone). There was no notable difference in the median time for testosterone recovery across the different treatment arms.

The above results demonstrated that the use of intensified AR blockade for a finite period has been found to PSA-PFS while maintaining a manageable safety profile and not interfering with testosterone recovery time. Consideration should be given to adding apalutamide to androgen deprivation therapy in high-risk BRPC patients.

Efficacy and safety of DaxibotulinumtoxinA in cervical dystonia

A recent study has shown that DaxibotulinumtoxinA (DAXI) is an effective and well-tolerated treatment for cervical dystonia (CD) when administered at doses of 125U and 250U. The study’s findings were published in the journal, Neurology.

ASPEN-1 was a phase 3 clinical trial that involved participants aged 18-80 years with moderate-to-severe CD. The study was randomized, double-blind, and placebo-controlled, with 301 participants receiving single-dose intramuscular DAXI 125U (n=125), 250U (n=130), or placebo (n=46). The change from baseline in Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) total score averaged across weeks 4 and 6 was the primary end point of this study, while duration of effect, Clinical and Patient Global Impression of Change (CGIC), (PGIC),TWSTRS subscale scores, and safety outcomes were the key secondary end points included.

DAXI 125U and 250U exhibited a substantial increase in the mean TWSTRS total score when compared to the placebo group (least squares mean [standard error] difference vs placebo: DAXI 125U, -8.5; DAXI 250U, -6.6). The median duration of effect with DAXI 125U was 24.0 weeks, while with DAXI 250U it was 20.3 weeks. Notable improvements were also seen in CGIC and PGIC responder rates, as well as TWSTRS subscales.

Therefore, it can be inferred that DAXI, administered at 125U and 250U dosages, could serve as an effective, long-acting, safe, and well-tolerated therapy for CD.

Aranesp more efficient in achieving target hemoglobin than Eprex, with less dose changes and minor complications

A recent study suggests that Aranesp Q weekly or every 2 weeks is more efficient than Eprex in achieving target Hb in hemodialysis (HD) patients. This study was published in the journal, International Urology and Nephrology.

This prospective, randomized, open-labeled study conducted for 24 weeks included 139 patients who were undergoing HD for >3 months and were >18 years of age, and on Eprex for >3 months. The patients were randomized into Aranesp group (A; n=72) and Eprex group (B; n=67). Patients in A group who were on Eprex Q TIW or BIW were converted to Aranesp Q weekly, by using the conversion factor of 200:1 and those on Eprex Q weekly were converted to Aranesp Q 2 weeks. On the other hand, B group patients continued on Eprex treatment. The primary end points of the study were percentage of patients achieving target Hb, number of dose changes in each group, and hemoglobin variability.

It was seen that target Hb was achieved in 64.8 % of the Aranesp and 59.7 % in the Eprex group. Mean number of dose changes was 1.3 and 1.9 in the Aranesp and Eprex groups, respectively. Also, the Hb variability was less frequent in the Aranesp group. Thus, it can be concluded that with less dose changes and minor vascular access complications, Aranesp Q weekly or every 2 weeks may be more efficient than Eprex in achieving target Hb in HD patients.

Bone biomarkers for overall survival in men with castration-resistant prostate cancer

According to a recent study, in newly diagnosed metastatic prostate cancer, high levels of bone turnover biomarkers are linked with a shorter lifespan, which are strongly prognostic for overall survival (OS). This study was published in the journal, European Urology.

This phase 3 study evaluated bone biomarkers in hormone-sensitive prostate cancer (HSPC) of 1279 men, out of which 949 had evaluable baseline bone biomarkers. The patients were randomly divided into training (n=316) and validation (n=633) sets. Cox proportional hazard models and recursive partitioning were employed. Bone resorption and bone formation markers were assessed from patient sera.

At the end of the study, it was found that after adjusting for clinical risk factors in the validation set, increased bone biomarkers were statistically significantly associated with an increased risk of death. As for the training set, three risk groups were identified with differential OS outcomes, after recursive partitioning algorithms were applied. The validation set confirmed these results.

Thus, it can be concluded that bone biomarkers may strongly and independently be prognostic for OS in men with HSPC initiating androgen deprivation therapy. These bone biomarker levels alone or in combination with clinical covariates, may help identify unique subsets of men with differential OS outcomes. In conclusion, high levels of bone turnover biomarkers are associated with a shorter lifespan in men with HSPC.