ARPIs May Improve Survival in Some With Prostate Cancer

A certain type of inhibitor has shown potential in improving overall survival in patients with metastatic castration-resistant prostate cancer.

In patients with metastatic castration-resistant prostate cancer, researchers have found that androgen receptor pathway inhibitors (ARPIs) outperformed the standard of care, which improved responses to treatment and overall survival (OS; time a patient lives, regardless of disease status).

Castration-resistant prostate cancer refers to the growth of cancer, even when the body’s testosterone levels are low, according to the National Cancer Institute.

Initial treatment typically consists of a testosterone blocker to prevent the hormones from activating the androgen receptor that produces the cancer cells, a news release about a study from Nature stated. However, the cancer cells become resistant to the treatment over time, so switching to different drugs, such as chemotherapy or second-generation hormone drugs to inhibit the androgen receptor (ARPIs), may help, according to the release.

“For the first time, we have compared these treatments with each other and also analyzed the DNA of the cancer cells to find out which drug that works best for different individuals,” Johan Lindberg, senior researcher in the Department of Medical Epidemiology and Biostatistics (MEB), Karolinska Institutet in Sweden, said in the news release.

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In the Nature study, for which Lindberg was an author, 193 patients with metastatic castration-resistant prostate cancer were included from Sweden, Belgium and Norway. Patients were randomly assigned to one of four treatment groups: treatment of the physician’s choice (64 patients); ARPIs (31 patients); taxanes (56 patients); or other investigational treatments (42 patients).

The median OS was evaluated in patients in each of these four treatment groups.

Of note, the status of circulating tumor DNA (ctDNA; amount of tumor cells in the bloodstream after the cells have died) was also found in the patient population, the researchers determined. This helped researchers randomize patients into each treatment group, the study noted, to help tailor the treatment as best as possible.

“It creates a self-learning system to continuously improve treatment for men with metastatic prostate cancer,” Martin Eklund, professor of epidemiology in the Department of Medical Epidemiology and Biostatistics (MEB), Karolinska Institutet, said in the release. “We are also gathering knowledge about which regions of the genome are important in prostate cancer.”

Regarding OS, the researchers found that patients in the ARPI treatment group had a median OS of 38.7 months versus 21.8 months in patients who were in the physician’s choice group, according to the study. The median OS was also higher in the ARPI group than in patients from the taxane group, whose median OS was 21.7 months.

Side Effects Experienced in the Study

Researchers from the study also compared the safety profiles of ARPIs and taxanes. The overall treatment-related side effect rate was higher in patients from the taxane group, compared with patients in the ARPI group, the researchers found.

Common side effects of any severity occurred in at least 5% of patients from both the ARPI and taxane groups were reported in the study. In the taxane group, common side effects experienced by patients included fatigue, back pain and anemia. Patients in the taxane group also commonly experienced higher rates of nausea, diarrhea, altered taste, constipation, peripheral sensory and general neuropathy.

In both the ARPI and taxane groups, common side effects experienced were hip pain, shortness of breath, fever and weight loss, as determined by the researchers. Blood events, such as thrombocytopenia (low platelet count) and neutropenia (low white blood cell count) were observed in patients from the taxane group but were not observed in patients from the ARPI group.

Side effect-related deaths occurred in three patients who were treated with taxanes, the researchers noted. They also established that overall, taxanes were linked to higher rates of general and treatment-related side effects, compared with ARPIs.

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