Enzalutamide the latest candidate for upfront prostate cancer therapy

GU cancer

By Michael Woodhead

3 Jun 2019

Enzalutamide has joined the rapidly evolving field of ‘upfront’ therapies for metastatic prostate cancer, although Australian trial results showed mixed results when used concurrently with docetaxel.

The potent androgen receptor inhibitor produced a significant improvement in overall survival when added to standard testosterone suppression therapy for patients with metastatic hormone-sensitive prostate cancer, according to interim results from the ENZAMET study presented at ASCO 2019 in Chicago.

The findings showed that enzalutamide could join docetaxel and abiraterone as potential upfront treatments for prostate cancer, the meeting was told, particularly for men who have a lower burden of metastatic disease.

The findings complemented other results for another drug in the same class – apalutamide – which was shown in the TITAN study to improve progression-free survival and overall survival in patients who had received prior treatment with docetaxel.

Study investigator Professor Christopher Sweeney, an Australian oncologist now working at the Dana-Farber Cancer Institute, Boston, said the ENZAMET study was unique in that it also included patients who had concurrent use of docetxel and enzalutamide, and it used standard non-steroidal anti-androgen therapy (NSAA) as an active control.

In the study, 1125 patients were randomised to standard testosterone suppression and either NSAA or enzalutamide 160mg day. More than 500 patients also received concurrent early docetaxel.

After three years, the overall survival rates were 80% for men in the enzalutamide arm and 72% for the active control group (Hazard Ratio 0.67).

Differences in overall survival were 90% vs 82% in men who had low volume metastatic disease compared to 71% vs 64% in men with high volume disease.

The increase in overall survival was only significant for men who did not receive docetaxel (83% vs 70%). This result may have arisen because a high proportion of patients who received docetaxel had high volume metastatic disease compared to those who did not have docetaxel (71% vs 37%), said Professor Sweeney.

He also noted that more adverse effects such as hypertension, fatigue, falls and cardiac events were seen with enzalutamide than with standard NSAA (42% vs 34%).

Nevertheless the findings showed that early enzalutamide therapy offered worthwhile benefits in overall survival and could help men go longer without having to take steroids or receive chemotherapy, he said.

“Physicians and patients with prostate cancer now have a new treatment option with enzalutamide and this is especially relevant for men who cannot tolerate chemotherapy and have a lower burden of disease on scans,” he said.

In an ASCO Plenary discussion on the findings, Dr Tanya Dorff an oncologist at City of Hope Hospital said the ENZAMET study had further vindicated the upfront intensification approach to metastatic prostate cancer that had started in 2014 with docetaxel.

She said that choosing between docetaxel, abiraterone and enzalutamide would require weighing up factors for patients such as length of treatment, which was short term for docetaxel but longer for the other two therapies. In contrast, patients may need to take time off work with docetaxel due to fatigue and experience side effects such as hair loss, she noted.

Patients and physicians would also have to weigh up the costs of different treatments, with docetaxel being relatively low cost and abiraterone about to come off patent, she added.

“We now have multiple options for upfront intensification and [as yet] no evidence that one is superior to the others,” she said.

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