Data from the randomized, phase 3, 4-arm PEACE-1 study were presented by Karim Fizazi, MD, PhD, during the Presidential Symposium at the ESMO Congress 2021 (abstract LBA5_PR). The trial began accruing patients back in 2013, and it has really mirrored the changing therapeutic landscape in advanced prostate cancer. Patients in the study were randomized to receive standard of care (SOC) consisting of androgen deprivation therapy (ADT) with docetaxel, SOC plus abiraterone, SOC plus radiotherapy, or SOC plus abiraterone and radiotherapy. The SOC was ADT plus docetaxel for 710 patients. It had been reported previously that the addition of abiraterone to ADT and docetaxel significantly improved radiographic progression-free survival in men with de novo metastatic hormone-sensitive prostate cancer (mHSPC) without adding significant short-term toxicity. Dr Fizazi presented an update on PEACE-1 with the now-mature overall survival data. In men with high-risk de novo mHSPC, adding abiraterone to ADT plus docetaxel resulted in a median lifetime gain of more than 1.5 years. This was striking, practice-changing data. Researchers combined the 2 abiraterone-containing arms in this analysis, and the impact of radiotherapy therapy is still not known.

To me, this was probably the most important study to come out of the ESMO Congress 2021. High-risk patients are obviously the patients with the worst prognosis. In my practice, if I were to see a patient with high-risk de novo mHSPC in the clinic this afternoon, I would review these data with him. Strengths of the study included its size and strong statistics, and the data showing benefits in both radiographic progression-free and overall survivals are compelling. We are going to need more time to understand the implications of this approach in lower-risk patients (eg, what does this mean for patients who evolve to metastatic prostate cancer?). While I do not think that we necessarily know the answer, this is compelling, and perhaps, in time, we will come to think about all mHSPC together, albeit noting differences in the natural history.

An update from the STAMPEDE trial was also shared during the Presidential Symposium at the ESMO Congress 2021 (abstract LBA4_PR). This analysis involved subsets from the STAMPEDE study with either nonmetastatic node-positive or high-risk, node-negative, locally advanced disease (ie, Gleason 8-10 and those with prostate-specific antigens in the 30s and 40s or higher). And recall that this arm of STAMPEDE was exploring the question of the addition of abiraterone to ADT. In the M1 group, there was a clear survival benefit with that approach, but in the M0 group, the benefit was not as clear. However, when you follow up the M0 group in node-positive high-risk patients, there is now a striking survival benefit in that group. So, these men are getting radiation therapy, 2 to 3 years of standard ADT, and now have had abiraterone added for 2 years. For that group of patients, although obviously a subset, the data were also very compelling.

Now, moving on to metastatic castration-resistant prostate cancer (mCRPC), another interesting study presented at the meeting was a phase 1/2 trial that assessed the combination of cabozantinib and atezolizumab in patients with measurable disease, which is, again, a subset of mCRPC (abstract LBA24). Cabozantinib has been tested in mCRPC, and, while researchers observed some activity, it did not meet any of the study end points. Of course, using a single-agent immune checkpoint in mCRPC has been disappointing to date in terms of its utility outside of patients who have microsatellite instability–high tumors or a high tumor mutational burden. This study showed an approximate 18% objective response rate with cabozantinib plus atezolizumab. There were several patients who had a durable long-term response, based on the long-term follow-up data. While subject to a number of caveats, the phase 3 trial that is now testing this combination seems well justified by the phase 2 data.