The latest results from the international ENZAMET clinical trial provide encouraging evidence that enzalutamide can help people with metastatic hormone-sensitive prostate cancer live longer and keep their cancer under control for many years.
Prostate cancer is driven by male sex hormones like testosterone. Androgen deprivation therapy (ADT) is a medical or surgical treatment to reduce levels of these hormones, and has been the mainstay of treatment of prostate cancer for decades. Enzalutamide acts to block the effects of remaining low levels of these hormones, and improves survival in prostate cancer that has grown despite ADT. ENZAMET (ANZUP 1304) compared enzalutamide, given alongside ADT and with or without a standard chemotherapy drug called docetaxel, with an older type of hormone treatment called a non-steroidal anti-androgen. The study included more than 1,100 participants and has now followed them for over 8 years on average, providing some of the longest-term information available for this type of treatment.
More participants were alive at eight years
At eight years, 50% of ENZAMET participants receiving enzalutamide were still alive, compared with 40% of those receiving the older hormone treatment.
We expected that some people would die of causes other than prostate cancer over such a long time, particularly in a group of participants who tended to be older. Deaths due to causes other than prostate cancer occurred at about the same rate in both groups. The improved overall survival was due to less prostate cancer deaths in the enzalutamide group. Across the study, prostate cancer was the cause of death in 207 participants receiving enzalutamide compared with 261 participants receiving the comparison treatment.
Cancer control lasted longer
Enzalutamide also provided longer-lasting control of prostate cancer. At eight years, 43% of participants receiving enzalutamide had not experienced clinical progression, compared with 20% of those receiving the older treatment. This was even more pronounced in participants with a favourable pattern of prostate cancer spread called “low volume” disease: 60% of participants with low volume disease had not experienced any growth of their cancer by 8 years.
A very low PSA was associated with better long-term outcomes
PSA is a blood test that often correlates with the amount of cancer in a person’s body. Changes in PSA can reflect whether the cancer is growing or responding to treatment. An exploratory analysis examined blood PSA levels seven months after starting treatment. Participants whose PSA had fallen to 0.2 ng/mL or lower were more likely to have better long-term outcomes. This PSA level was achieved by 67% of participants receiving enzalutamide, compared with 48% receiving the older treatment.
Among participants who reached this PSA level, 55% were alive at eight years, compared with 23% of those whose PSA remained above 0.2 ng/mL.
These findings are exploratory and should not be used on their own to predict an individual patient’s outcome.
Many participants remained on treatment for years
The long-term results also showed that enzalutamide could be continued for many years. One-third of participants originally assigned to enzalutamide were still receiving treatment at eight years, compared with 14% receiving the older treatment, and three quarters of participants assigned to enzalutamide did not need a dose modification of enzalutamide. Of the participants still on enzalutamide at 8 years, almost 90% had not required any changes in dose, meaning that they had been able to manage the side effects of treatment for at least that long without a dose reduction.
No new safety signals emerged with longer follow-up. However, falls were more common with enzalutamide, which is particularly relevant when considering treatment for more frail patients.
What does this mean for patients?
These long-term ENZAMET results show that the benefits of enzalutamide seen earlier in the study continue with extended follow-up. Participants receiving enzalutamide lived longer, experienced longer control of their prostate cancer and, for many, were able to remain on treatment for years.
Importantly, while enzalutamide can provide prolonged cancer control, it does not stop advanced prostate cancer from eventually progressing in everyone. For many people, however, it has become an important foundation of treatment, helping to delay the spread of cancer while maintaining quality of life and allowing treatment to continue over the longer term.
These results add to the evidence supporting enzalutamide plus ADT as an important treatment option for people with metastatic hormone-sensitive prostate cancer, while also highlighting the importance of tailoring treatment to the individual. Factors such as age, overall health, frailty, treatment side effects and risk of falls all need to be considered when deciding which treatment is most appropriate.