Enzalutamide offers survival advantage over other NSAAs in mHSPC

 

Medical writer: Dave Levitan

Enzalutamide and testosterone suppression significantly prolonged overall survival compared with other nonsteroidal anti-androgens (NSAAs) and testosterone suppression in men with metastatic hormone-sensitive prostate cancer (mHSPC), according to the interim analysis from the phase III ENZAMET trial (Abstract LBA2).

Enzalutamide is a potent direct inhibitor of the androgen receptor (AR), with established benefit in castration-resistant prostate cancer. ENZAMET randomly assigned 1,125 men with mHSPC to either testosterone suppression and other NSAAs, including bicalutamide, nilutamide, or flutamide (562 patients), or testosterone suppression and enzalutamide (563 patients).

On May 31, results of the TITAN study (Abstract 5006) were presented, showing that the addition of another AR inhibitor, apalutamide, can significantly improve survival when added to androgen-deprivation therapy; this was regardless of prior docetaxel use. ENZAMET adds to that body of evidence, although it is the first trial to examine the use of enzalutamide with or without concurrent docetaxel; 45% of patients in the enzalutamide group and 44% in the NSAA group received docetaxel, and 61% of those patients had a high volume of metastases. The men were followed for a median of 34 months.

Christopher Sweeney, MBBS, of the Dana-Farber Cancer Institute, discussed results from an interim analysis of the trial during a press briefing on June 2; the study was also presented during the Plenary Session. Patient characteristics were similar between the two groups, with a median age of approximately 69. Most of the study was conducted in Australia, New Zealand, Canada, the United Kingdom, Ireland, and the United States.

At 36 months, 80% of the enzalutamide group remained alive, compared with 72% of the NSAA group (HR 0.67, 95% CI [0.52, 0.86]; P = 0.002). Enzalutamide also resulted in a significant increase in the time to prostate-specific antigen rise, clinical progression, or death (HR 0.39, 95% CI [0.33, 0.47]; P < 0.001). The same was true for a delay in the time to clinical progression, based on imaging, worsening of symptoms, change of therapy, or death (HR 0.40, 95% CI [0.33, 0.49]; P < 0.001).

The overall survival difference was seen specifically in men who did not receive docetaxel, but there was no significant difference among those who did. The 3-year overall survival rate in those who did receive docetaxel was 74% with enzalutamide and 75% with other NSAAs; in those who did not receive docetaxel, those rates were 83% with enzalutamide and 70% without it. Of the 588 patients with a high volume of metastases, 61% received docetaxel; Dr. Sweeney pointed out that in other studies the survival outcomes for patients with a high volume is poorer than for those with lower volume.

Dr. Sweeney said the toxicity profile was similar to previous reports with enzalutamide. The rate of serious adverse events per year of therapy exposure was similar between the groups. There was more grade 3 fatigue with enzalutamide vs. NSAA (6% vs. 1%, respectively), as well as more grade 3 syncope (4% vs. 1%, respectively) and grade 3 hypertension (8% vs. 4%, respectively). Seven patients in the enzalutamide group experienced seizures (1%), compared to none in the NSAA group.

“Enzalutamide added to testosterone suppression represents an appropriate option for men with metastatic prostate cancer commencing testosterone suppression,” Dr. Sweeney said. “The benefits are clear in patients with both low and high volume of metastases.”

ASCO Expert Neeraj Agarwal, MD, of the Huntsman Cancer Institute, called the overall survival difference “remarkable” and said during a press briefing on June 2 that the study increases his confidence that targeting AR is likely the best approach in this setting. “In my view, using enzalutamide early on will allow our patients to avoid chemotherapy and steroids for many years, thus hopefully improving their quality of life,” he said.

Tanya B. Dorff, MD, of City of Hope, was the discussant for the abstract during the Plenary. She said that these results continue a “revolution” that began in 2015 with the data from the CHAARTED trial, when it began to become clear that intensified up-front treatment is beneficial. “With ENZAMET, the trend of increased benefit with intensified treatment upfront was validated,” she said.

There are trade-offs with the use of agents like enzalutamide or abiraterone, she noted, with the potential for added toxicity and the need to take the agents over an extended period of time; however, docetaxel requires a shorter course of treatment but potentially more debilitating side effects.

“We anticipate that upfront trials will continue to yield major advances, especially as molecular stratification and novel agents are added into the paradigm,” Dr. Dorff said.



Posted on 15 July 201917 May 2024