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The addition of abiraterone acetate (Zytiga) to standard therapy with docetaxel plus androgen deprivation therapy (ADT) significantly improved overall survival in patients with de novo metastatic castration-sensitive prostate cancer, as reported at the European Society for Medical Oncology virtual meeting.

In this exclusive 番茄社区 video, , of Massachusetts General Hospital in Boston, breaks down the details of the .

Following is a transcript of his remarks:

Hi, my name is Xin Gao and I'm a medical oncologist at Mass General Cancer Center, where I focus on treatment of prostate cancer and cancers of the urinary tract. I want to thank 番茄社区 for the invitation to provide some of my thoughts on, in my opinion, likely practice-changing abstracts on expanding the role of abiraterone acetate in prostate cancer patients that were recently presented at the European Society for Medical Oncology Congress meeting in September of 2021.

So diving right into the first abstract, PEACE-1, this is a phase III trial conducted at multiple centers in Europe involving a 2×2 factorial design in which close to 1,200 patients with de novo metastatic castration-sensitive prostate cancer were randomly assigned to one of four treatment arms: standard of care, standard of care plus abiraterone, standard of care plus radiotherapy, or standard of care plus abiraterone and radiotherapy.

The co-primary endpoints were radiographic progression-free survival and overall survival. And the trial sought to evaluate the efficacy of adding abiraterone to standard of care, as well as the role of adding radiotherapy to standard of care. And, notably, standard of care for metastatic castration-sensitive prostate cancer patients has really evolved over the course of this study, which started back in 2013. And this study adapted and incorporated upfront docetaxel into the standard-of-care treatment over time.

The first results of this study were actually presented at the ASCO annual meeting in June of 2021 by Dr. Karim Fizazi, who now presents some pretty exciting updates to the data at ESMO. So at ASCO the data showed significantly improved radiographic progression-free survival with the addition of abiraterone to ADT plus docetaxel. But overall survival data were not yet mature at that time.

Now at the ESMO Congress, updated data at 3.8 years of median follow-up were presented. And the headline is that the addition of abiraterone to ADT plus docetaxel resulted in significant overall survival benefit, as well as maintaining the previously reported radiographic progression-free survival benefit.

So, the baseline demographics, 355 patients assigned to each arm, so standard of care, which involved ADT plus docetaxel, or standard of care plus abiraterone -- so ADT plus docetaxel plus abiraterone. Sixty-four percent of the patients had high-volume de novo metastatic disease, and overall survival significantly improved by adding abiraterone to ADT plus docetaxel -- hazard ratio of 0.75, according to a 25% improvement in overall survival.

All subgroups appeared to benefit with the addition of abiraterone, but the overall survival benefit seemed more pronounced, I would say, in those with high-volume disease, with a hazard ratio of 0.72. And the median overall survival in these patients was 5.1 years with the triplet therapy compared to just 3.5 years without abiraterone. So that's a median overall survival [difference] of 1.6 years, pretty significant.

For low-volume disease patients, the hazard ratio was 0.83. So still favoring the addition of abiraterone, but less pronounced, and notably the data remain immature for low-volume patients due to the small number of deaths at the time of follow-up. The radiographic progression-free survival benefit was similar to what was previously reported at ASCO and remained significant. Adding abiraterone to ADT plus docetaxel resulted in a 50% improvement in radiographic progression-free survival, with a median rPFS of 4.5 years for the triplet combination compared to just 2.0 years for ADT plus docetaxel alone.

And the benefit, again, slightly greater in patients with high-volume disease burden, with a hazard ratio of 0.47, compared to those with low-volume disease, where the hazard ratio was 0.58. But the groups appear to benefit in terms of rPFS. Both groups appear to benefit.

So it's thought that the combination therapy with the triplet is indeed better than sequential therapy in this case. And then finally the triplet combination appeared to be reasonably well-tolerated in terms of adverse events or side effects. The rates of significant liver toxicity and hypertension were higher with the addition of abiraterone, at 6% and 22%, respectively, for grade 3 or higher AEs. But the rates of significant neutropenia, febrile neutropenia, fatigue, GI toxicities, and cardiac toxicities appear to be pretty similar between the two arms.

I did want to note that the deaths related to adverse events occurred in seven patients in the ADT plus docetaxel plus abiraterone arm compared to just three patients in the ADT plus docetaxel arm. I think it's unclear if this is really a significant difference, but I do think that it's something worth following and noting in the long-term follow-up.

So, in summary, I think the headline for the PEACE-1 presentation is quite impressive, in that the addition of abiraterone to ADT plus docetaxel led to significant improvements in overall survival, particularly in high-volume disease patients, where the median difference was 1.6 years of benefit, and also maintained a really great radiographic progression-free survival benefit of 2.5 years improvement in all-comers.

All of this occurred with a regimen that appeared to be reasonably tolerated, albeit with some increases in liver toxicity and hypertension that I think should be noted and followed up with longer-term follow-up.

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