Category: 2019

The treatment landscape for metastatic prostate cancer is shifting and expanding yet again, according to new findings from two large clinical trials presented at the 2019 annual meeting of the American Society of Clinical Oncology (ASCO). The ENZAMET trial tested the drug enzalutamide (Xtandi) and the TITAN trial tested apalutamide (Erleada) in men whose cancer is still responsive to hormone-suppressing therapies—also called castration-sensitive prostate cancer. In both trials, combining the respective drugs with the androgen deprivation therapy (ADT) substantially improved how long men lived overall and how long they lived without their cancer getting worse.

The ENZAMET trial enrolled more than 1,100 men with hormone-sensitive metastatic prostate cancer. The men were randomly assigned to ADT combined with enzalutamide or with any of three other androgen-blocking drugs. At a median follow-up of nearly 3 years, men who received ADT plus enzaluatamide had a 33% reduced risk of death, with 80% still alive compared with 72% of men treated with ADT plus another antiandrogen drug. Men in the enzalutamide group also had better clinical progression-free survival (PFS), which the research team defined as the time until the return of disease-related symptoms, the detection of new metastases on imaging scans or the initiation of another cancer treatment for prostate cancer, whichever came first. At 3 years, 63% of men in the enzalutamide group were alive without clinical progression of their disease, compared with 33% in the standard treatment group. Although enzalutamide appeared to be effective regardless of whether men had high- or low-volume disease, one apparent differentiating factor was planned early treatment with docetaxel (taxotere). Nearly half of the men in both treatment groups received early treatment with docetaxel and, for those men, enzalutamide was not associated with longer overall survival.

From the standpoint of efficacy, similar results were seen in the TITAN trial with apalutamide (Erleada). Funded by the drug’s manufacturer, Janssen Pharmaceuticals, the trial enrolled more than 1,000 men with hormone-sensitive, metastatic prostate cancer, with participants randomly assigned to receive ADT along with a placebo or ADT plus apalutamide. At 2 years of follow-up, approximately 82% of men who received ADT plus apalutamide were still alive compared with 74% in men treated with ADT plus placebo, for a 33% reduction in the risk of death. The trial’s other primary measure was the amount time men lived without evidence on imaging scans that their disease had progressed, known as radiographic PFS. At a median follow-up of nearly 2 years, men treated with ADT plus apalutamide had a 50% improvement in radiographic PFS than men treated with ADT alone.

What factors would influence the choice of treatments? In the case of enzalutamide and apalutamide, Dr. William Dahut, clinical director of the National Cancer Institute’s Center for Cancer Research said, both drugs “may be particularly good choices for men with low-volume disease, who might shy away from docetaxel” due to concerns about side effects. Unlike docetaxel, which must be administered intravenously in the hospital, enzalutamide, apalutamide, and abiraterone are oral drugs that can be taken at home, so they also offer greater convenience for patients. On the other hand, many patients tolerate docetaxel quite well, Dr. Dahut noted, and it’s given for a fixed duration, not continuously like the other drugs. Other factors such as insurance costs may also affect treatment choice.

For additional details, see the following article published June 19th, 2019 on line by the National Cancer Institute (NCI) Cancer Currents Blog.

A recent study presented on May 3-6 at the American Urological Association’s 2019 Meeting found that treating metastatic, hormone-resistant prostate cancer (mCRPC) patients (who had not received chemotherapy) with Xtandi (enzalutamide) leads to better survival outcomes and lower healthcare costs than Zytiga (abiraterone acetate).

While therapies that lower male sex hormones (testosterone) — required for prostate cancer to survive and grow — are a mainstay of therapy for advanced prostate cancer, most patients will eventually acquire resistance to such approaches. This often happens because the cellular receptor for these hormones, called the androgen receptor, becomes constantly active, even in the absence of androgens. Therapies that inhibit the androgen receptor — such as Pfizer and Astellas’ and Xtandi and Janssen’s Zytiga — have largely improved the overall survival of prostate cancer patients, and are now approved for mCRPC patients in the U.S. and Europe. However, which treatment brings the most benefits or the lowest healthcare costs has not been addressed.

In this study, researchers performed a retrospective study to compare the overall survival and healthcare costs associated with these two second-generation androgen receptor inhibitors. They examined data from 3,174 adult men with mCRPC who had not received chemotherapy for at least one year before starting treatment with either Xtandi or Zytiga. Patients had been treated between April 2014 and March 2017, and their data were recovered from the Veterans Health Administration (VHA) database. Overall, 1,945 patients, mean age 73, received Zytiga, while Xtandi was administered to the remaining 1,229 patients, mean age 74.

After examining outcomes of these patients, researchers found that those on Xtandi lived for a median of 30 months, compared to 26 months for Zytiga. This represented a significant 17% reduction in mortality risk with Xtandi. Xtandi-treated patients also required fewer outpatient visits — both overall and cancer-related — than those treated with Zytiga, indicating that Xtandi led to a reduced use of medical resources. In line with this, Xtandi patients had fewer healthcare costs than Zytiga patients. In total, a patient treated with Xtandi would have a monthly healthcare cost of $8,085, compared to $9,092 for Zytiga. Prostate cancer-related costs were also lower for Xtandi — $6,321 versus $7,280.

Thus, researchers concluded that “chemotherapy-naive mCRPC patients treated with Xtandi had better survival, significantly lower resource use and healthcare costs than patients treated with Zytiga.”

The above appeared in the e mail Prostate Cancer News Today, May 16th, 2019.

Treatment with the radioactive molecule lutetium-177-PSMA-617 (LuPSMA), which binds to the prostate-specific membrane antigen, is a potential therapeutic strategy for patients with metastatic castration (hormone)-resistant prostate cancer (CRPC), results from a Phase II pilot study suggest.

Prostate-specific membrane antigen (PSMA) is found at high levels in prostate cancers, particularly in patients with hormone-resistant disease — a form of cancer that no longer responds to hormone therapy and continues to progress. More research is assessing the potential of using agents that target this protein to deliver radioactive compounds directly into cancer cells. The LuPSMA molecule is composed of an anti-PSMA antibody bound to the radioactive compound Lutetium-177. Its safety and efficacy are being assessed in a pilot Phase 1/2 study by researchers at the Peter MacCallum Cancer Centre, Melbourne, Australia.

The trial enrolled 50 metastatic CRPC patients whose tumors were positive for the PSMA factor. Their cancer had progressed after standard treatments, including hormone therapy and chemotherapy, and they were offered four doses of LuPSMA, each given six weeks apart. Participants had rapidly progressing disease, taking 2.6 months to double their PSA levels — a marker of prostate cancer. Most patients had received the chemotherapies docetaxel (Taxotere; 84%) and  cabazitaxel (Jevtana; 48%). Hormone therapy with Zytiga (abiraterone), Xtandi (enzalutamide) or a combination of both had been given to 90% of patients.

The study’s primary goals were to measure the number of patients whose PSA levels dropped and the treatment’s toxicity. Additional objectives included imaging responses, time patients lived without disease worsening, overall survival, and quality of life scores.

Investigators reported a reduction in PSA levels by at least 50% in 64% of patients, including 44% who experienced a reduction of at least 80%. Among the 27 patients with measurable disease at the study’s start, 56% experienced a partial or complete tumor reduction. The median time patients lived without disease worsening — measured through a rise in PSA levels — was 6.9 months. Their median overall survival was 13.3 months. A total of 14 patients received additional LuPSMA doses after their disease progressed. In nine of these patients (64%), PSA levels reduced by at least 50%. The most common side effects were dry mouth, nausea, and fatigue. Serious side effects were rare and included abnormally low levels of platelets and anemia, both detected in 10% of cases.

Overall, these early findings confirm the “high response rates and low toxicity with LuPSMA in men who had progressed after standard therapies,” even “in patients who subsequently progressed and were administered further LuPSMA,” the researchers wrote. “These results have provided the basis for randomised controlled trials currently underway,”

These findings were shared in a poster presented at the  2019 Genitourinary Cancers Symposium, Feb. 14–16 in San Francisco.