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Experts Explain Impact of LATITUDE Abiraterone Data in Prostate Cancer

Angelica Welch and Danielle Bucco
Published: Wednesday, Aug 02, 2017

Jorge A. Garcia, MD
Jorge A. Garcia, MD
Adding abiraterone acetate (Zytiga) plus prednisone to androgen deprivation therapy (ADT) lowered the risk of death by 38% in men with newly diagnosed, high-risk, metastatic prostate cancer, according to findings from the phase III LATITUDE trial presented at the 2017 ASCO Annual Meeting.

After a median follow-up of 30.4 months, the median overall survival (OS) had not yet been reached in the abiraterone cohort and was 34.7 months with ADT alone (HR, 0.62; 95% CI, 0.51-0.76; <.0001). The 3-year OS rates were 66% with abiraterone versus 49% in the control arm. Median PFS was 33 months versus 14.8 months, respectively (HR, 0.47; 95% CI, 0.39-0.55; P <.0001).

During the ASCO meeting, OncLive discussed these practice-changing findings with Jorge Garcia, MD, Department of Hematology and Oncology, Cleveland Clinic, and Kim Chi, MD, associate director of clinical research, Vancouver Prostate Centre.

OncLive: Please provide the background for the LATITUDE trial.

Garcia: The standard of care for many years for men with prostate cancer has been castration, oftentimes orchiectomy or we do ADT therapy, which is basically hormonal suppression. That treatment protocol changed a couple years ago with the results of CHAARTED and also with STAMPEDE, where we demonstrated that adding docetaxel to ADT lead to survival improvement in men with castration-sensitive metastatic disease.

So, since a couple years ago, the standard for us has been ADT and chemotherapy. Now, the caveat with that data is the benefit that we have seen with adding chemotherapy appears to be derived only for patients with high-volume metastases. For high-volume metastases, the intergroup data in America has been somewhat arbitrary but has been used for many years. Which is, men with visceral disease, men who have more than 3 bone lesions, 1 of which has to be outside of the pelvis or spine, and a Gleason score of 8 or greater.

LATITUDE, as well as the second arm from STAMPEDE, looked at the addition of abiraterone acetate to the backbone of ADT, which is what we reviewed at ASCO. Around 1000 castration-sensitive patients were randomized to either ADT plus placebo, or ADT plus oral therapy with abiraterone and prednisone. The primary endpoint was survival, and the hazard ratio for that was actually 0.62, an almost 38% risk reduction in mortality if you get abiraterone upfront with ADT. 

In LATITUDE, we looked at 2 out of those 3 risk factors for inclusion for the definition of high-volume disease, which is, again, different than what we saw for CHAARTED. So, if we look at the makeup of patients with a Gleason score of 8 or higher in CHAARTED, it’s roughly the same number of patients that we have seen in LATITUDE. So, to us, the patient population is basically the same—there isn’t much difference in the makeup of those patients.

I think the important part is, adding abiraterone upfront not only makes people live longer, but also reduces the risk of relapse by more than double, 14 months for ADT alone versus 33 months with ADT and abiraterone. The addition of abiraterone delayed progression, skeletal-related events, PSA declines, and time to chemotherapy, as well, so it is a pretty powerful trial. 

Were you surprised by the results?

Chi: What surprised me in the analysis when I first saw it several months ago was the degree of benefit. I do not think any of us were expecting this. Since it was a high-risk or poor prognosis patient population, the degree of benefit was a good surprise. Additionally, the secondary endpoints were also in favor of the combination therapy.

This was a first interim analysis, which makes it more remarkable, because the study was very positive, showing an overall survival advantage for patients who received androgen deprivation therapy with abiraterone and prednisone. The hazard ratio was 0.62, meaning there was a 38% reduction in the risk of death. The P value was less than .0001, showing that this study is very positive and, therefore, all the other patients who were on placebo were crossed over. Not only was this the first interim analysis, it is also now the final analysis.

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