Arun Azad, PhD, an associate professor at Peter MacCallum Cancer Centre and the University of Melbourne; fellow at Victorian Cancer Agency; and chair of the ANZUP Cancer Trials Group Translational, discusses the significance of the PROfound trial in metastatic castration-resistant prostate cancer (mCRPC).

 evaluated the efficacy and safety of olaparib (Lynparza) versus abiraterone acetate (Zytiga) or enzalutamide (Xtandi) in patients with mCRPC who progressed on prior hormonal anticancer treatment and harbored 

Results showed that olaparib significantly improved overall survival compared with enzalutamide or abiraterone.

​Moreover, as an early example of ​the efficacy of precision medicine in ​men with prostate cancer, these data garnered significant excitement, Azad adds.

As such, several ongoing studies are now evaluating combinations with PARP inhibitors in earlier disease settings​, Azad says.

Ultimately, the PROfound study set the stage for precision medicine in the advanced prostate cancer space, Azad concludes.

Videos

Arun Azad, PhD, discusses the significance of the PROfound trial in metastatic castration-resistant prostate cancer. 

Dr. Azad on the Significance of the PROfound Trial in mCRPC

Arun Azad, PhD, an associate professor at Peter MacCallum Cancer Centre and the University of Melbourne; fellow at Victorian Cancer Agency; and chair of the ANZUP Cancer Trials Group Translational, discusses the design of the ​phase 3ARCHES trial in metastatic hormone-sensitive prostate cancer (mHSPC).

​The ARCHES study randomized patients with mHSPC to receive androgen deprivation therapy with enzalutamide (Xtandi) or placebo.

The trial was designed to evaluate ​all men with mHSPC ​rather than evaluating 1 specific subtype, says Azad.

Notably, the study included men with low​- and high​-volume mHSPC, ​men with newly diagnosed and relapsed​/refractory ​mHSPC, and ​men who previously received docetaxel.

Additionally, ARCHES was a multicenter, international study​; thus, the data are widely applicable, Azad concludes.

Arun Azad, PhD, discusses the design of the ​phase 3ARCHES trial in metastatic hormone-sensitive prostate cancer.

Dr. Azad on the Design of the ARCHES Trial in mHSPC

Arun Azad, PhD, an associate professor at Peter MacCallum Cancer Centre and the University of Melbourne; fellow at Victorian Cancer Agency; and chair of the ANZUP Cancer Trials Group Translational, discusses the utility of adding enzalutamide (Xtandi) to androgen deprivation therapy (ADT) in subgroups of men with metastatic hormone-sensitive prostate cancer (mHSPC).

Two pivotal studies have demonstrated the benefit of adding enzalutamide to ADT in patients with mHSPC, says Azad. The phase 3 ARCHES study examined ADT plus or minus enzalutamide in men with mHSPC. This trial included patients with low-volume and high-volume metastatic, newly diagnosed, and relapsed metastatic disease. The primary end point of the trial was radiographic progression-free survival.

The study met its primary end point, showing a significant benefit with the addition of enzalutamide to ADT across all patient subgroups analyzed, concludes Azad.

Arun Azad, PhD, discusses the utility of adding enzalutamide to androgen deprivation therapy in subgroups of men with metastatic hormone-sensitive prostate cancer.

Dr. Azad on the Benefit of Adding Enzalutamide to ADT in mHSPC

Arun Azad, PhD, an associate professor at Peter MacCallum Cancer Centre and the University of Melbourne; fellow at Victorian Cancer Agency; and chair of the ANZUP Cancer Trials Group Translational, discusses the results of the post-hoc analyses of the phase 3 ARCHES trial in men with metastatic hormone-sensitive prostate cancer (mHSPC).

The post-hoc analyses, which were presented virtually during the 2020 ESMO Congress, evaluated whether baseline prostate-specific antigen (PSA) influenced outcomes in patients with mHSPC who had prior exposure to androgen deprivation therapy (ADT), explains Azad. 

Notably, over 90% of patients enrolled on the ARCHES study had received prior ADT, Azad says. Moreover, 18% had received prior docetaxel.

As such, patients’ baseline PSA levels upon enrollment were different than their baseline levels at diagnosis, Azad explains. 

Patients were stratified by baseline PSA levels of 0.2 µg/L or less (n = 134), greater than 0.2 µg/L but less than 4 µg/L (n = 372), and greater than 4 µg/L (n = 541).

Notably, results of the analyses showed a clinical benefit in terms of radiographic progression-free survival and other key secondary end points with the addition of enzalutamide (Xtandi) plus ADT versus placebo plus ADT, irrespective of baseline PSA levels prior to starting enzalutamide, Azad concludes. 

Arun Azad, PhD, discusses the results of the post-hoc analyses of the phase 3 ARCHES trial in men with metastatic hormone-sensitive prostate cancer.  



Dr. Azad on the Post-Hoc Analysis of the ARCHES Study in mHSPC           

Arun Azad, PhD, an associate professor at Peter MacCallum Cancer Centre and the University of Melbourne; fellow at Victorian Cancer Agency; and chair of the ANZUP Cancer Trials Group Translational, discusses unmet needs for men with metastatic hormone-sensitive prostate cancer (mHSPC).

The management of patients with mHSPC has changed considerably in the past 5 years, says Azad. In addition to androgen deprivation therapy (ADT), the field now has strong evidence indicating that the use of docetaxel chemotherapy or 1 of the androgen receptor  antagonists improves survival, adds Azad. 

At the same time, this disease remains lethal for most patients, says Azad. Additional strategies are needed to further improve outcomes. These approaches could include new combinations, the addition of novel drugs to existing drugs, a better selection of existing drugs, treatment of the primary disease itself, and the identification of biomarkers, adds Azad.

Ultimately, the biggest untapped resource is using agents that are already in the arsenal, according to Azad. Data have read out in the United Kingdom, the United States, and Australia and show that the vast majority of patients are not getting access to these ne​wer therapeutic strategies. They are still being treated with ADT alone. 

It is known that this results in an undertreatment of the vast majority of patients with mHSPC, says Azad. Implementing clinical trial data into real-world practice is a key unmet need for these patients, concludes Azad.

Arun Azad, PhD, discusses unmet needs for men with metastatic hormone-sensitive prostate cancer.

Arun Azad, PhD

Articles

Dr. Azad on the Significance of the PROfound Trial in mCRPC

Dr. Azad on the Design of the ARCHES Trial in mHSPC

Dr. Azad on the Benefit of Adding Enzalutamide to ADT in mHSPC

Dr. Azad on the Post-Hoc Analysis of the ARCHES Study in mHSPC

Dr. Azad on Unmet Needs in Metastatic Hormone-Sensitive Prostate Cancer