ENZARAD or ANZUP 1303 was a phase three international investigator-initiated randomized trial and it enrolled from eight countries 802 patients with a median follow-up of eight years the eight countries were Australia New Zealand we have the UK Ireland the rest of the EU and then also the United States and, the key question in Enzalutamide is, can we improve metastasis-free survival by adding two years of enzalutamide to patients with high-risk, clinically localized or locally advanced prostate cancer, receiving high-dose radiation and two years of a GnRH agonist...
ENZARAD or ANZUP 1303 was a phase three international investigator-initiated randomized trial and it enrolled from eight countries 802 patients with a median follow-up of eight years the eight countries were Australia New Zealand we have the UK Ireland the rest of the EU and then also the United States and, the key question in Enzalutamide is, can we improve metastasis-free survival by adding two years of enzalutamide to patients with high-risk, clinically localized or locally advanced prostate cancer, receiving high-dose radiation and two years of a GnRH agonist. Now, I will say, in the control arm, we did give six months of a non-steroidal anti-androgen. The primary endpoint was metastasis-free survival, and this was defined based on conventional imaging. We’re talking CT, MRI, or bone scan, and this is based on the ICECAP definition that was a surrogate for overall survival. So we did not include PSMA PET positive findings as a metastasis endpoint. In terms of the power of the study, we had an 80% power to detect a 33% reduction in the hazard of metastasis or death before metastasis. So in terms of the primary endpoint, we did not find a benefit to metastasis-free survival with the addition of enzalutamide. The hazard ratio was 0.88 and it crossed one. The p-value was 0.34 and at eight years the difference was 74% metastasis-free survival in the patients who got enzalutamide and 72% metastasis-free survival in the patients who did not get enzalutamide. There was a difference in PSA, progression-free survival. The hazard ratio there was 0.44. The difference was 67% versus 62% at eight years, and the hazard ratio was 0.78. No difference in overall survival, no difference in prostate cancer mortality, but I do want to say that there’s a certain success story here in that both arms did really well from a prostate cancer-specific survival perspective. It was 97% at eight years in the enzalutamide group, 96% at eight years in the non-steroidal antiandrogen group, saying that really patients with a high-risk prostate cancer these days getting treated with high-dose radiation and two years of regular GnRH agonists are doing really well in terms of their outcomes. Now, there were two very important subgroups. So we had pre-specified five subgroups and pre-stratified by them. But two of them that I want to call out that were positive. So one of them is whether or not you were clinically node positive. For the clinically node positive patients by CT or MRI, there was a statistically significant interaction, p-value of 0.04, such that those who were node positive had a significant benefit to MFS from enzalutamide. The hazard ratio there was 0.43, and it did not cross one. Whereas for patients who were clinically node negative, there was no benefit for enzalutamide. The hazard ratio was about 0.95. The other subgroup that was significant was those who were selected for pelvic lymph node radiation. Remember, actually, I didn’t mention this, but pelvic lymph node radiation was optional in our trial. And so if you were clinically node negative, so investigators could declare. But if you were clinically node positive, which was 11% of our trial, you had to get pelvic lymph node radiation. So of the patients who got pelvic lymph node radiation, there was a significant benefit to enzalutamide. The MFS hazard ratio was 0.47. For those who did not get pelvic lymph node radiation, the hazard ratio was 1.25. And so how do we put this together? We think that for most patients with high-risk localized prostate cancer in the modern era, getting high-dose radiation and two years of hormone therapy, most patients don’t need enzalutamide. But for those two subgroups of patients, for patients who are clinically node positive, and for those patients who have another indication for pelvic lymph node radiation, I think that there is some good evidence from Enzalutamide to add enzalutamide. So that’s kind of the summary, but happy to discuss some more.
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