In addition to the data from the STAMPEDE trial already reported, the data from the LATITUDE trial (NCT01715285) will also be presented at ASCO this afternoon — and they are also positive.
Fizazi et al. enrolled exclusively men newly diagnosed with high-risk, metastatic, hormone therapy-naive prostate cancer (mHNPC). The patients had to be newly diagnosed ≤ 3 months prior to randomization and they had to have ECOG scores of 0 to 2 (i.e., they had to be asymptomatic or have a relatively low level of symptomatic disease).
The patients also had to have at least two out of three other risk factors:
- A Gleason score of 8 to 10
- Three or more bone lesions
- Measurable visceral metastases
These are similar to the types of men who were shown to benefit from treatment with androgen deprivation therapy (ADT) + docetaxel in the CHAARTED trial.
They enrolled a total of 1,199 patients who were then randomized 1:1 to treatment with either
- ADT + placebos for abiraterone acetate and prednisone (i.e., standard care, as in the STAMPEDE trial, but without radiation) or
- ADT + abiraterone acetate + prednisone
Co-primary end points for this study were overall survival (OS) and radiographic progression-free survival (rPFS).
Here are the results, which had become evident at the time of the first, planned, interim analysis — and led to the decision to stop the trial immediately so that men on the control arm could be switched to the more active combination therapy:
- The median follow-up was 30.4 months.
- There had been 406 deaths (i.e., 48 percent of patients) and radiographic progression among 593 patients).
- Both primary endpoints and all secondary endpoints significantly favored ADT+ abiraterone acetate + prednisone.
- In terms of overall survival (OS)
- Average (median) overall survival for men of ADT + placebos was 34.7 months.
- Average (median) overall survival was not reached for men on ADT + abiraterone acetate + prednisone
- This difference was statistically significant (hazard ratio [HR] = 0.62; p < 0.0001).
- In terms of radiographic progression-free survival (rPFS)
- Average (median) rPFS for men of ADT + placebos was 14.8 months.
- Average (median) rPFS was 33.0 months for men on ADT + abiraterone acetate + prednisone
- This difference was statistically significant (HR = 0.47; p < 0.0001).
- Grade 3/4 adverse events included
- Hypertension in 20.3 percent of the patients treated with ADT + abiraterone + prednisone compared to 10.0 percent of patients treated with ADT alone.
- Hypokalemia (low potassium levels) in 10.4 percent of the patients treated with ADT + abiraterone + prednisone compared to 1.3 percent of patients treated with ADT alone.
- Increased ALT (5.5 vs 1.3 percent) or AST (4.4 vs 1.5 percent).
The authors conclude that
- Early use of abiraterone acetate + prednisone added to ADT in patients with high-risk mHNPC yielded significantly improved OS, rPFS, and all secondary endpoints vs ADT and placebos alone.
- ADT + abiraterone acetate + prednisone had a favorable risk/benefit ratio and supports early intervention with abiraterone acetate + prednisone in newly diagnosed, high-risk mHNPC.
The “New Prostate Cancer InfoLink would again note that the increase in risk for side effects from the early use of abiraterone acetate + prednisone is not minimal, and that clinicians will therefore need to monitor patients with caution on this type of therapy.
Filed under: Diagnosis, Living with Prostate Cancer, Management, Risk, Treatment |
THE "NEW" PROSTATE CANCER INFOLINK 
So I guess I’m not a candidate for this treatment being Gleason 9 with no visceral mets and one 9 mm bone metastasis found with an Axumin scan? I’m back on ADT3, am having the bone metastasis treated with three fractions of 9 grays per fraction with SBRT and will start on Xgeva.
Dear Bob:
In fact you do appear to be a candidate for this type of treatment. Read the entry criteria again. You only had to be metastatic and have one of the three high-risk criteria, not all three. However, the FDA hasn’t approved abiraterone acetate for this indication yet.
Sitemaster
The trial says patients needed 2 out of 3. I have only one: high G score. I’m glad I don’t qualify and hope I never do.
My mistake. It’s been a busy day and I was thinking of the STAMPEDE trial data. However, I would also point out that just because you qualify for a particular type of treatment never means that you “have to” have such treatment.
My husband isn’t newly diagnosed. Assuming he is not a candidate. He was diagnosed nearly 5 years ago: Stage IV, metastatic — bones and lymph node involvement. Please respond.
Dear Ellen:
This is actually a hard question to answer because there is now an argument that men like your husband, who have metastatic prostate cancer that is currently being controlled with just standard androgen deprivation therapy ADT or “hormone” therapy might, in fact, benefit from the immediate early addition of abiraterone acetate (Zytiga) to their current therapy.
This is really something you will need to talk to your doctors about.
However, a problem is going to be that this use of abiraterone acetate is not yet approved by the FDA and so insurance companies and Medicare may need some time to determine whether they can and will cover the costs of this early use of abiraterone acetate. They should. Of that there is no doubt, but … It is not a cheap drug and so if all the men in America who are on ADT for metastatic disease suddenly started getting treatment with abiraterone acetate too, the cost would be very considerable.
This is