Zytiga (Abiraterone) Plus Prednisone Approved for Treatment of Earlier Form of Metastatic Prostate Cancer

On February 8th, the Janssen Pharmaceutical Companies of Johnson & Johnson announced that the U.S. Food and Drug Administration (FDA) has approved a new indication for Zytiga® (abiraterone acetate) in combination with prednisone for the treatment of patients with metastatic high-risk hormone-sensitive prostate cancer (HSPC). The approval is based on Phase 3 data from the pivotal LATITUDE clinical trial, which found that in patients with metastatic high-risk HSPC, Zytiga® in combination with prednisone reduced the risk of death by 38% compared to placebos.

This approval marks an important step in addressing the unmet needs of patients with metastatic high-risk hormone-sensitive prostate cancer by providing an option that has demonstrated improvement in overall survival.  Zytiga® (abiraterone acetate) plus prednisone could become a standard of care for these patients.

LATITUDE was a multinational, multicenter, randomized, double-blind, placebo-controlled clinical trial that examined the use of Zytiga® 1,000 mg once daily in combination with prednisone 5 mg once daily, compared to placebos in patients with newly diagnosed, metastatic high-risk HSPC, who had not received prior cytotoxic chemotherapy. All the patients received a gonadotropin-releasing hormone (GnRH) analog or had prior bilateral orchiectomy. The study data were presented at the plenary session of the 2017 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago, and simultaneously published in The New England Journal of Medicine. The study showed Zytiga® in combination with prednisone reduced the risk of death by 38% compared to placebos. Additional data demonstrated statistically significant delay in time to initiation of chemotherapy for patients in the Zytiga® arm compared to those in the placebo arm.

The Phase 3, multinational, multicenter, randomized, double-blind, placebo-controlled LATITUDE study enrolled 1,199 patients with newly diagnosed metastatic, high-risk hormone-sensitive prostate cancer (HSPC), who had not received prior cytotoxic chemotherapy. The study was conducted at 235 sites in 34 countries in Europe, Asia-Pacific, Latin America, and Canada. A total number of 597 patients were randomized to receive Zytiga® plus prednisone, while 602 patients were randomized to receive placebo. All patients received a gonadotropin-releasing hormone (GnRH) analog or had prior bilateral orchiectomy. High-risk disease was defined as having at least two of three risk factors at baseline: a total Gleason score of ≥8, presence of ≥3 lesions on bone scan, and evidence of measurable visceral metastases. Patients with significant cardiac, adrenal, or hepatic dysfunction were excluded. The median duration of treatment with Zytiga® and prednisone was 24 months.

Zytiga® (abiraterone acetate) in combination with prednisone is now indicated for the treatment of patients with metastatic hormone-resistant prostate cancer (HRPC) and with metastatic high-risk hormone-sensitive prostate cancer (HSPC). For additional details, see the following link.

Big Anxieties, Little Faith

God provides! Whose anxious? Photo: BJ Gabrielsen

As part of the Sermon on the Mount, Jesus spoke the following words from Matthew 6:25-30 about worry and anxiety, emotions and feelings most of us with prostate cancer can relate to. “Do not be anxious for your own life, what you shall eat, or what you shall drink; nor for your body as to what you shall put on. Is not life more than food and the body more than clothing? Look at the birds of the air, that they do not sow, neither do they reap nor gather into barns, and yet your heavenly Father feeds them.  Are you not worth much more than them? And which of you by being anxious can add a single cubit to his life span?” (A cubit is 18 inches and ‘life span’ as used here can mean ‘height’). “Observe how the lilies of the field grow; they do not toil. Yet Solomon in all his glory did not clothe himself like one of these. But if God so arrays the grass of the field,….will He not much more do so for you, O men of little faith.”

Stressful situations come in a variety of forms and intensities, and our earthly existence will never be completely free of them. However the important question is what are we going to do with our anxiety? If we let it dominate our thinking, fretfulness can become a way of life. But if we believe and trust in what the Bible says about the Lord and His care for us, then we will experience an awesome liberation from worry.

Do you sometimes doubt whether God really cares about your health issues like cancer that cause you (and me) to worry? After all, He’s got the entire universe to run and our issues seem so small in comparison, and we are just one person in this cosmos. But consider how inconsequential birds and flowers are, yet Jesus says that the Father cares for them. Don’t you think we are worth much more to Him than they are? (Actually the woodpecker in the picture lives in my yard).

At times we let ourselves get all worked up and stressed out because we are trying to change something that is beyond our control. While there may be ways of improving our disease states by proper diet, exercise, rest and proper treatments, there are many situations that we are powerless to alter such as the length of our life. But the sovereign Ruler of the universe loves us and holds everything in His hands – including our stressful and seemingly out-of-control situations. Therefore, we have no reason to fret or fear.

Perhaps the biggest reason we worry is because we don’t trust the Lord or do not even know Him or have a relationship with Him. Anxiety can be a symptom of unbelief. The Bible is filled with God’s promises to provide, but so often we doubt that He will. If you have a relationship with God, and if you can trust Him for your eternal security, can’t you also trust Him for your earthly needs? Submit your needs to Him and trust Him. If you are not sure of your relationship with God, see the following link.

A portion of the above was taken from In Touch devotional by Dr. Charles Stanley.

Apalutamide (ARN-509) Approved to Treat Non-Metastatic, Hormone-Resistant Prostate Cancer

On Feb. 14th, the U.S. Food and Drug Administration approved apalutamide (Erleada®, previously  called ARN-509) for the treatment of non-metastatic, castration (hormone)-resistant prostate cancer (CRPC). Apalutamide could be administered in a clinical setting wherein men who are being treated with androgen (hormone) deprivation therapy (ADT) see their PSA levels begin to rise, but no metastases are visible yet on bone or CT scans. There were previously no FDA-approved treatments for non-metastatic CRPC, and patients typically continued to receive ADT, despite its diminishing benefit.

This FDA approval was based on results from a randomized phase 3 SPARTAN clinical trial presented at the February 2018 ASCO Genitourinary Cancers Symposium. The SPARTAN trial tested apalutamide versus placebo and whatever treatment the men were already given (mostly ADT), in 1,207 non-metastatic CRPC patients with rapidly rising PSA levels of doubling time 10 months or less. Patients selected for the trial had no distant metastases based on bone and computed tomography (CT) scans of the pelvis, abdomen, chest and head. Some patients had malignant local or regional (pelvic) lymph nodes no larger than  2 cm on the short axis.

Apalutamide was found to delay the time to metastatic disease by over 24 months on average (40.5 months in the apalutamide group vs. 16.2 months in the placebo group). This represents a 72% reduction in risk of metastasis or death. The full results have been published in the New England Journal of Medicine.

This website recently contained a blog on ARN-509 and the SPARTAN trial posted on November 10th, 2017. The similarities between apalutamide (ARN-509) and enzalutamide were noted.  Their chemical structures are indeed very similar. They differ only in two areas of the molecule where chemists who develop drugs would anticipate making changes. Enzalutamide contains a 5-membered heterocyclic ring with a carbon-sulfur double bond whereas apalutamide contains a carbon-oxygen double bond (carbonyl) in its place. In addition, enzalutamide contains a dimethyl group on heterocyclic ring whereas this is replaced by a fused cyclobutyl ring in apalutamide. Further comparisons and similarities will be noted in future posts.


A Phase 3 Trial Shows that Xtandi Reduces the Risk of Metastasis in Hormone-Resistant Prostate Cancer

According to results just recently presented at the February 2018 Genitourinary Cancers Symposium in San Francisco, treatment with Xtandi® (enzalutamide) reduced the risk of metastasis or death in hormone-resistant prostate cancer (CRPC) patients whose cancer has not yet spread beyond the prostate, Pfizer and Japan-based Astellas Pharma recently announced.

The Phase 3 PROSPER clinical trial evaluated whether adding Xtandi® to the standard androgen (hormone) deprivation therapy (ADT) was better than ADT alone in patients whose cancer had progressed based on rising PSA levels.  The 1,401 men in the study had increasing PSA levels, but no symptoms nor prior evidence of metastases. The Xtandi® –  ADT combination extended the time a patient remained alive and metastasis-free by nearly two years, compared to ADT alone. Patients with non-metastatic, hormone-resistant cancer are those whose prostate cancer worsens despite reduction of the amount of testosterone to very low levels with anti-androgen therapies. In such patients with non-metastatic CRPC, there is a high unmet need to delay development of metastases and the progression to advanced prostate cancer. There are currently no approved systemic therapies for patients with non-metastatic CRPC in the U.S.

The multi-national, double-blind PROSPER study (NCT02003924) assessed the safety and effectiveness of a once-daily, oral, 160 mg dose of Xtandi®, an androgen receptor inhibitor approved for treatment of advanced prostate cancer, in 1,401 men with CRPC on standard treatment with androgen deprivation therapy (ADT). Adding Xtandi® to standard ADT reduced the risk of developing metastases or death by 71% compared with ADT alone. Specifically, the combo treatment extended the time until a patient developed metastasis or died – the study’s primary endpoint – from 14.7 months to 36.6 months.

Xtandi® plus ADT also led to a 93% decrease in the relative risk of PSA worsening, delayed median time to PSA progression by 33.3 months, and prolonged median time to first use of antineoplastic (anticancer) therapy by 21.9 months, compared to ADT alone. Subsequent follow-up will enable the analysis of changes in overall survival, another of the study’s secondary endpoints.

Side effects with Xtandi® were consistent with those reported in prior studies in patients with metastatic CRPC taking this medication. Grade 3 (severe) or higher adverse events were observed in 31% of men taking Xtandi® plus ADT, compared to 23% with ADT alone. The most frequent severe events were hypertension and fatigue. In addition, major adverse cardiovascular events occurred in 5% of patients receiving Xtandi® plus ADT – compared to 3% with ADT alone. The group taking the combination treatment also reported three seizures (none in those taking ADT alone). Treatment discontinuation primarily due to adverse events was low with both treatments.

The information above was published on February 12th in Prostate Cancer News Today to which I heartily recommend a subscription.