Dr Grimm on the Rationale for Conducting a Post-Hoc Analysis of ARASENS in mHSPC

Marc-Oliver Grimm, MD, professor, chairman, Department of Urology, Jena University Hospital, 

discusses the rationale for conducting a post-hoc analysis

 of the phase 3 ARASENS trial (NCT02799602) in patients with metastatic hormone-sensitive prostate cancer (mHSPC).

The ARASENS trial was designed to evaluate the efficacy of a triplet therapy consisting of darolutamide, androgen deprivation therapy (ADT), and docetaxel in patients with mHSPC. This combination was compared with a control arm, in which patients received docetaxel plus ADT and a placebo, Grimm begins. The primary results from this trial demonstrated a significant reduction in the risk of death for the triplet therapy group vs the placebo group, he reports.

The rationale behind the post-hoc analysis of the ARASENS trial was to gain insights into the treatments patients received after their disease progressed and how these treatments influenced their outcomes, Grimm says. Specifically, the analysis focused on the differences in post-progression therapies that these patients received. It was found that patients who received the triplet therapy had no difference in post-progression survival regardless of whether they were subsequently treated with an androgen receptor pathway inhibitor (ARPI) or non-ARPI treatments, he elucidates. However, these patients experienced rapid progression on subsequent therapies after receiving the initial triplet combination, Grimm states. Despite this, the significant advantage was that these patients remained in the mHSPC stage for a longer duration, which is associated with a better quality of life, minimal pain, and delayed progression, according to Grimm.

In the placebo group, patients who progressed and were treated with ARPI therapies, such as abiraterone acetate (Zytiga) or enzalutamide (Xtandi), had better outcomes compared with those treated with non-ARPI therapies, such as docetaxel or cabazitaxel (Jevtana), he expands. This finding highlights the potential benefits of ARPI treatments in extending survival post-progression for patients initially treated with ADT and docetaxel, he concludes.

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Marc-Oliver Grimm, MD, discusses a post-hoc analysis of the ARASENS trial in metastatic hormone-sensitive prostate cancer.

Dr Grimm on Unmet Needs After Progression to mCRPC Following ARPI Plus Chemo

Marc-Oliver Grimm, MD, professor, chairman, Department of Urology, Jena University Hospital, discusses the unmet needs for patients who progress to metastatic castration-resistant prostate cancer (mCRPC) following treatment with an androgen receptor pathway inhibitor (ARPI), androgen deprivation therapy (ADT), and chemotherapy in the hormone-sensitive setting. He also highlights future steps of research following a post-hoc analysis of the phase 3 ARASENS trial (NCT02799602).

The analysis sought to evaluate post-progression survival in patients with metastatic hormone-sensitive prostate cancer (mHSPC) who received darolutamide (Nubeqa) in combination with ADT and docetaxel compared with those who received placebo plus ADT and docetaxel.

The analysis, which was presented at the 

, revealed that darolutamide plus ADT and docetaxel increased overall survival compared with placebo plus ADT and docetaxel, and this regimen also delayed the time to progression to mCRPC. Following progression, patients treated with the darolutamide regimen had similar survival outcomes irrespective of subsequent therapy selection. However, patients who received the placebo regimen experienced prolonged survival when subsequent treatment included an ARPI vs non-ARPI therapies, which were primarily chemotherapy.

Grimm notes that results from the post-hoc analysis highlight a persisting need for more effective treatment options for patients who progress to mCRPC following treatment with an ARPI and chemotherapy. Additional analysis of the ARASENS trial is ongoing.

Marc-Oliver Grimm, MD discusses the clinical implications, short comings, and future steps following a post-hoc analysis from the phase 3 ARASENS trial.

Dr Grimm on Post-Progression OS After Darolutamide Plus ADT/Docetaxel in mHSPC 

Marc-Oliver Grimm, MD, professor, chairman, Department of Urology, Jena University Hospital, discusses findings from a post-hoc analysis from the phase 3 ARASENS trial (NCT02799602). The analysis sought to evaluate post-progression survival in patients with metastatic hormone-sensitive prostate cancer (mHSPC) who received darolutamide (Nubeqa) in combination with androgen deprivation therapy (ADT) and docetaxel compared with those who received placebo plus ADT and docetaxel.

Grimm emphasizes the benefits of the triplet combination, particularly for younger patients. He noted that patients receiving the triplet therapy demonstrated prolonged survival in the mHSPC state and were generally associated with improved quality of life and minimal pain progression. This suggests a significant advantage in maintaining patients in the mHSPC state for an extended period, he says.

The analysis revealed that darolutamide plus ADT and docetaxel not only increased overall survival compared with placebo plus ADT and docetaxel, but the triplet also delayed the time to progression to metastatic castration-resistant prostate cancer (mCRPC). Additionally, patients treated with the darolutamide regimen had similar survival outcomes with all post-progression therapies, irrespective of treatment with another androgen receptor (AR) pathway inhibitor or chemotherapy. Conversely, patients receiving the placebo regimen experienced faster progression to mCRPC, and subsequent treatment with an AR pathway inhibitor improved survival vs non–AR pathway inhibitor therapies, which were primarily chemotherapy.

Grimm also highlights that although the triplet therapy offered significant initial benefits, there is a critical need for new treatment modalities for patients who progress after receiving chemotherapy and radical prostatectomy. This underscores the importance of ongoing research to develop new therapeutic strategies for patients with mHSPC post-progression, particularly for those who have exhausted standard treatment options.

Marc-Oliver Grimm, MD discusses darolutamide in combination with androgen deprivation therapy and docetaxel in mHSPC.

Marc-Oliver Grimm, MD

Articles

Dr Grimm on the Rationale for Conducting a Post-Hoc Analysis of ARASENS in mHSPC

Dr Grimm on Unmet Needs After Progression to mCRPC Following ARPI Plus Chemo

Dr Grimm on Post-Progression OS After Darolutamide Plus ADT/Docetaxel in mHSPC