Combination treatments for metastatic disease
Clinicians and researchers gathered last month at the American Society of Clinical Oncology Genitourinary Cancers Symposium (ASCO GU) — some in-person in San Francisco, some tuning in virtually. Hundreds of presentations covered advances in screening, diagnosis, treatment, monitoring, and survivorship in prostate and other GU cancers.
Results of two key clinical trials presented offer promising approaches to treating metastatic prostate cancer (prostate cancer that has spread to other parts of the body). This is important because although prostate cancer is highly treatable when diagnosed at an early stage, metastatic disease can be deadly.
ARASENS trial results: Triplet treatment of metastatic hormone-sensitive prostate cancer
Metastatic hormone-sensitive prostate cancer (mHSPC) is prostate cancer that has spread outside the prostate and can be controlled (i.e., stops growing) with hormone therapy (also known as androgen deprivation therapy or ADT). Current treatments include ADT, often combined with radiation therapy, docetaxel chemotherapy, and/or an approved newer androgen receptor-directed therapy.
ARASENS is a large randomized clinical trial that enrolled 1300 patients with mHSPC. The study looked at whether adding the newest androgen receptor-directed therapy medication darolutamide to standard ADT + docetaxel could help men live longer.
The results were strongly positive: patients who received the “triplet” combination of ADT + docetaxel + darolutamide decreased the risk of death by 32% compared with patients who received the standard of care (ADT + docetaxel) + placebo. Other measures, such as the time to develop resistance to ADT, also favored the triplet combination. Not only was adding darolutamide more beneficial, it was also safe: it did not increase side effects.
Although it is not yet FDA-approved in the U.S. specifically for mHSPC, in the future, darolutamide may become part of the new standard of care for this disease.
MAGNITUDE trial results: A novel combination against metastatic castration-resistant prostate cancer
In metastatic castration-resistant prostate cancer (mCRPC), patients who have previously received hormone therapy see their tumors begin to grow, and sites of metastatic disease can be found on imaging scans. New approaches to treating mCRPC are urgently needed, with over 34,000 men projected to die of prostate cancer in 2022.
Medications called PARP inhibitors were approved in 2020 for patients with mCRPC who have certain changes in genes that repair damaged DNA. Combining treatments that attack cancer cells in different ways may be synergistic. The MAGNITUDE clinical trial tested one such combination.
In this trial, patients with mCRPC were randomized to treatment with abiraterone + prednisone + the PARP inhibitor niraparib OR abiraterone + prednisone + placebo and followed for about 18 months. Investigators measured outcomes such as disease progression and death.
The results showed that in patients with changes in genes that repair damaged DNA (such as BRCA1 or BRCA2), adding niraparib was beneficial: patients receiving abiraterone + prednisone + niraparib were 27% less likely to have disease progression on scans or death compared to patients receiving only abiraterone + prednisone. In the subset of patients who had changes in the specific genes BRCA1 or BRCA2, the benefit was even larger: niraparib was linked to nearly 50% lower risk of disease progression or death. Conversely, patients without such gene changes did not benefit from adding niraparib.
Regarding side effects, there were no new problems with safety. However, more patients in the niraparib group had moderate to severe side effects, and more patients discontinued treatment. Quality of life was similar between the two treatment groups.
This is an example of precision medicine. Not all prostate cancers are the same, and for some therapies, we can use genes and other markers to select patients for whom the therapy may work better.
Niraparib is currently FDA-approved to treat certain other cancers. These promising trial results may be considered during the FDA approval process of niraparib for prostate cancer.