Apalutamide (ARN-509) & the SPARTAN Trial.

[pjoshea13]

(Apalutamide might be an improvement on Xtandi.)

I mentioned SPARTAN 2 years ago (pasted from [1]), but no results have yet been published:

"In September 2013, J&J initiated the development of a major, randomized, double-blind, Phase III clinical trial of ARN-509 (the ... SPARTAN study) in the treatment of non-metastatic, castration-resistant prostate cancer (nmCRPC), aiming to enroll a total of about 1,200 patients (see also the relevant trial information on ClinicalTrials.gov)."

"... eligible patients must have no sign of evident metastatic prostate cancer and must have either high risk for disease progression, defined as a PSA doubling time of ≤ 10 months while on continuous androgen deprivation therapy (ADT), or castration-resistant prostate cancer demonstrated while the patient has been on continuous ADT."

"All patients will remain on their current therapy when they are enrolled into the SPARTAN trial, when they will then be randomized to additional treatment with either ARN-509 (at 240 mg once daily) or a placebo."

"The SPARTAN study is enrolling patients at some 420 clinical sites around the world (in the USA and also in Australia, Canada, many European countries, Israel, Japan, New Zealand, Russia, and Taiwan) ...

"Current expectations are that the SPARTAN trial will be fully enrolled by late in 2016 and that final trial results can be expected some time in 2019. Patients are expected to be followed for up to 5 years, with a primary study endpoint "

...

A few days ago [2]:

"Janssen Biotech has submitted a new drug application to the U.S. Food and Drug Administration (FDA) for an investigational, next-generation therapy called apalutamide (ARN-509) to treat non-metastatic castration-resistant prostate cancer.

"Apalutamide is an oral androgen receptor inhibitor that blocks the action of testosterone in prostate cancer cells.

"The submission was based on data from the Phase 3 SPARTAN clinical trial (NCT01946204), an ongoing study of the safety and efficacy of apalutamide versus placebo, in men with non-metastatic castration-resistant cancer who have a rapidly rising prostate specific antigen (PSA), despite receiving continuous androgen deprivation therapy (ADT).

"Because patients with rapidly rising PSA levels are at increased risk for metastatic disease, the primary objective of the trial was to assess metastasis-free survival, or the time from randomization to first evidence of confirmed metastasis (the spread of cancer cells to another part of the body).

"Janssen revealed that patients receiving ADT plus apalutamide lived significantly longer without metastatis, compared to those receiving ADT plus a placebo. But the company did not disclose any further details. Additional data from the SPARTAN trial should be presented at a future medical meeting, the company said.

“The SPARTAN data lead the path towards a new approach to treating men with prostate cancer earlier in the disease course. We have demonstrated that treating patients before the disease has metastasized improves outcomes,” Peter Lebowitz, MD, PhD, global therapeutic area head of oncology at Janssen, said in a press release. “We are thrilled to have completed our submission of the SPARTAN data to the FDA and we look forward to a promising treatment that can provide new hope and expectations for men facing this disease.”

"Castration-resistant prostate cancer is an advanced form of the disease associated with poor survival rates. Men who receive ADT to treat non-metastatic prostate cancer can eventually become resistant to treatment and develop the more advanced form.

"Studies have estimated that between 10 and 20 percent of patients diagnosed with prostate cancer might develop the castration-resistant form within about five years. Moreover, metastatic castration-resistant prostate cancer is associated with deterioration in quality of life and few therapeutic options.

"Apalutamide is the first agent submitted to treat non-metastatic cancer-resistant prostate cancer. The New Drug Application is the vehicle through which a new drug is formally proposed to the FDA before marketing in the United States. The data gathered through animal and human studies become part of the process, which is supposed to tell a drug’s whole story, including what happened during the clinical tests, what the ingredients of the drug are, the results of animal studies, how the drug behaves in the body, and how it is manufactured, processed, and packaged.

"Then, if safety and efficacy is proven, if the drug’s proposed labeling is appropriate, and if the drug’s identity, strength, quality, and purity are demonstrated, the FDA reviews the submission and decides whether to approve the new drug."

-Patrick

[1] prostatecancerinfolink.net/...

[2] prostatecancernewstoday.com...

[pjoshea13]

Why the rush? Looks like the similar [PROSPER] trial using Xtandi, also has some good (unpublished) intermediate results.

-Patrick

[Hidden]

I find this pretty interesting, Patrick.

I was taking part in the ARN-509 study almost a year and a half ago. I left the study, and my Uro at the time, because they couldn't get in agreement as to whether I had mets or not. And, they were both looking at the same imaging. I certainly did have mets. So, this tells me that J&J was willing to keep me on this study, although it was for non-met patients. I was floored that something like this could happen. Now I wonder how often it does happen.

Joe

[pjoshea13 in reply to Hidden]

Joe,

The following exclusion criterion for SPARTAN is clear enough:

"Presence of confirmed distant metastases, including central nervous system and vertebral or meningeal involvement"

My own experiences with the art of reading scans makes me wary. In 2015, I was told that I had mets to ribs, collar bone & somewhere else - plus L5. My radio-oncologist dismissed all but the L5 - which he agreed to treat as an oligo-met. In other words, two extreme readings of the same scan.

In 2016, my wife had a similar experience. Her oncologist said that she had multiple plasmacytomas & treated her as though she had multiple myeloma. After the chemo, she was scheduled to undergo stem cell replacement at Wake Forest. When we arrived for the first consultation, the response was "Are you crazy? You have a solitary plasmacytoma. There is a 2.5% probability of dying during the procedure. Don't do it."

-Patrick