Futher to my post of 2 years ago: "Zytiga & ADT - NEJM Paper" [1]
we now have the Final Analysis [2], & an interview with one of the authors [3].
"The study findings found abiraterone acetate and prednisone plus ADT continued to demonstrate an improvement in overall survival, hazard ratio (HR) = 0.66, meaning a 34% decrease in the risk of death associated with the use of ADT with abiraterone and prednisone. The median overall survival, which had not been reached before in the ADT with abiraterone and prednisone arm, was 53.3 months compared to 36.5 months for ADT plus placebo, prolonging median overall survival by 16.8 months."
"In addition to meeting the primary endpoints, the study also met secondary endpoints that were in favor of the abiraterone acetate and prednisone plus ADT therapy tied to pain progression, time to skeletal-related events, time to chemotherapy initiation and time to subsequent prostate cancer therapy. In terms of subsequent prostate cancer therapy, approximately 60 percent of patients receiving ADT plus placebo received life-extending subsequent therapy. It is also important to note that time to second disease progression (PFS2), which is defined as the time from randomization to progression on subsequent therapy, was also significantly in favor of abiraterone acetate and prednisone plus ADT. This implies that patients getting subsequent therapy don’t actually ever catch up to the patients receiving abiraterone acetate upfront."
PatrickWould these favorable results also apply to someone like me with metastatic hormone sensitive PCa on IADT after RP, SRT and multiple RT tx to mets?
Study details: "abiraterone acetate plus prednisone with androgen-deprivation therapy in patients with newly diagnosed, metastatic, castration-sensitive prostate cancer" [1], above.
You are metastatic & castration-sensitive but not newly diagnosed.
I dug this out from the Protocol [1] - pages 20-22 (easier to read) - see 4.2.5:
"4.1. Inclusion Criteria
Each potential subject must satisfy all of the following criteria to be enrolled in the study:
1. Willing and able to provide written informed consent
2. Men age 18 years and older
3. Newly diagnosed metastatic prostate cancer within 3 months prior to randomization with histologically or cytologically confirmed adenocarcinoma of the prostate without neuroendocrine differentiation or small cell histology.
4. Distant metastatic disease documented by positive bone scan or metastatic lesions on CT or MRI.
5. Two of the following high-risk prognostic factors:
Gleason score of ≥8
Presence of 3 or more lesions on bone scan
Presence of measurable visceral (excluding lymph node disease) metastasis
(RECIST 1.1)
6. Eastern Cooperative Oncology Group (ECOG) performance status grade of 0, 1 or 2
(Attachment 1) Approved, Date: 31 July 2012
20
JNJ-212082 (abiraterone acetate)
7. Adequate hematologic, hepatic, and renal function:
hemoglobin 9.0 g/dL independent of transfusions
neutrophils 1.5 x 109/L
platelets 100 x 109/L
total bilirubin 1.5X upper limit of normal (ULN) [except for subjects with documented Gilbert’s disease in which case total bilirubin not to exceed 10X ULN]
alanine (ALT) and aspartate (AST) aminotransferase 2.5X ULN
9. Agrees to use a condom and another effective method of birth control if he is having sex with a woman of childbearing potential or agrees to use a condom if he is having sex with a woman who is pregnant
4.2. Exclusion Criteria
Subjects who meet any of the following criteria will be excluded from participating in the study:
1. Active infection or other medical condition that would make prednisone use contraindicated
2. Any chronic medical condition requiring a higher systemic dose of corticosteroid than 5 mg prednisone per day
3. Pathological finding consistent with small cell carcinoma of the prostate
4. Known brain metastasis
5. Any prior pharmacotherapy, radiation therapy, or surgery with curative intent for metastatic prostate cancer. The following exception is allowed:
Up to 3 months of ADT with LHRH agonists or orchiectomy with or without concurrent anti-androgens prior to subjects’ randomization is permitted
Subjects may have one course of palliative radiation or surgical therapy to treat symptoms resulting from metastatic disease (e.g., impending cord compression or obstructive symptoms) if it was administered prior to randomization. Radiation or surgical therapy could not have been initiated 4 weeks after the start of ADT or orchiectomy.
6. Uncontrolled hypertension (systolic blood pressure ≥160 mmHg or diastolic BP ≥95 mmHg). Subjects with a history of hypertension are allowed provided blood pressure is controlled by anti-hypertensive treatment
7. Active or symptomatic viral hepatitis or chronic liver disease Approved, Date: 31 July 2012
21
Clinical Protocol 212082PCR3011
JNJ-212082 (abiraterone acetate)
8. History of adrenal dysfunction
9. Clinically significant heart disease as evidenced by myocardial infarction, or arterial thrombotic events in the past 6 months, severe or unstable angina, or New York Heart Association (NYHA) Class II-IV heart disease or cardiac ejection fraction measurement of <50% at baseline (Attachment 2)
10. Atrial fibrillation, or other cardiac arrhythmia requiring pharmacotherapy
11. Other malignancy (within 5 years), except non-melanoma skin cancer
12. Administration of an investigational therapeutic or invasive surgical procedure (not including surgical castration) within 30 days of Cycle 1 Day 1 or currently enrolled in an investigational study
13. Any condition or situation which, in the opinion of the investigator, would put the subject at risk, may confound study results, or interfere with the subject’s participation in this study
NOTE: Each subject will be reviewed by Sponsor before randomization to ensure that the eligibility criteria have been met.
Thanks. So if one is still hormone sensitive after many tx like me does adding Zytiga extend OS enough to be worth it? I believe I saw somewhere that it only added 3 months.
I can't answer that, but the old idea of adding a drug only after the failure of another one never made sense to me. If one is targetting the androgen receptor axis, why leave an escape hatch open for the cancer? Cancer cells can evolve to make DHT from a pathway that does not require T - so why not add Avodart? Cancer cells can make androgens from cholesterol, & can even make cholesterol - so why not add a statin? Zytiga is not just about stopping androgens being made from adrenal hormones, it blocks the use of pregnenolone & progesterone within the cancer cells.
The idea is that by blocking all the escapes one can think of, we put off resistance far longer, potentially, than the old sequential use approach. Overall survival is a different issue.
Forgive me for sounding so ignorant, but this trial for Zytiga + ADT versus ADT alone (placebo)? My dad has been successfully treated with Lupron +Casodex for nearly four years. He did have six rounds of chemo in 2015. I wonder with research such as this if it would be wise for him to switch to Zytiga?
I'm glad that he has had a good run on Lupron + Casodex. Would it be wise to switch before resitance occurs? I can't answer that, but I would be tempted.
Unfortunately for me this regimen only controlled my PSA for just 6 months, having dropped from 20 to 0.12 but now steadily rising to 0.55 in most recent 3 months since my RARP. I am BRCA2+ and Gleason 10.
Zytiga/Prednisone now stopped. Continuing on Eligard. Just started on 50 mg Casodex plus Olaparib. Will also be having Provenge treatment, which is pending approval for me; should be hearing in the coming days. Also waiting for insurance to approve Axumin PET scan. Hitting it hard.
Great news from TommyTV. Now, my MO ordered Xtandi. Then at next "meeting", while I had a needle in arm and was getting last chemo cycle she was talking Zytiga. When I mentioned there was an order for Xtandi already she does a neat flip and says oh that's right, do the Xtandi. I wonder how that will compare to the Zytiga. I've seen a couple of vague conflicting references.
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