According to a press release issued by Astellas and Pfizer that the FDA has granted a priority review to enzalutamide (Xtandi) for the treatment of men with metastatic hormone-sensitive prostate cancer.

Currently, Xtandi, which is an androgen receptor inhibitor, is only approved for men with castration-resistant prostate cancer.  The FDA “granted a supplemental new drug application for the additional indication priority review based on results from two phase 3 trials.  The trials include “the ARCHES trial, results of which were presented at this year’s Genitourinary Cancers Symposium and published in Journal of Clinical Oncology,” and the “ENZAMET trial, presented during the plenary session at this year’s ASCO Annual Meeting and published in the New England Journal of Medicine.”

In a report from the 2019 ASCO Meeting, it was shown that after a median follow-up of 14.4 months men with metastatic hormone sensitive prostate cancer (mHSPC) who were treated with Xtandi (enzalutamide) along with ADT (hormone therapy) had significantly improved radiographic progression-free survival, regardless of their prior treatment.

The analysis was done in a phase III study of 1150 men with metastatic hormone-sensitive prostate cancer (mHSPC).  They were randomized to Xtandi plus ADT or placebo plus ADT. The men were also stratified by disease volume and prior docetaxel (chemotherapy) treatment to determine treatment efficacy. Of these men, 18% had received prior docetaxel, and 91% had received previous ADT or had an orchiectomy. 

After a median follow-up of 14.4 months, the men who had Xtandi along with ADT experienced an improved radiographic progression-free survival advantage over those who had only ADT, regardless of their prior treatment. 

The study also showed that both cohorts of men experienced a similar frequency of grade 3/4 (the most severe) adverse events.

http://abstracts.asco.org/239/AbstView_239_266457.html

Another inspiring presentation at the 2019 ASCO meeting was an interim analysis of the international, randomized phase III ENZAMET trial.  

The trial found that 80% of men with metastatic hormone-sensitiveprostate cancer who received enzalutamide (Xtandi) along with standard-of-care treatment (ADT) were alive after three years, compared with just 72% of men who received other nonsteroidal antiandrogens along with standard ADT therapy. These findings were presented by Sweeney et al. (Abstract LBA2).

“Physicians and patients with prostate cancer now have a new treatment option with enzalutamide, and this is especially relevant for men who cannot tolerate chemotherapy and have a lower burden of disease seen on scans,” said study Co-Chair Christopher Sweeney, MBBS, a medical oncologist at the Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, Boston.

“In men with metastatic prostate cancer starting testosterone suppression, enzalutamide and docetaxel are both active and are reasonable alternatives, but they have different side effects, costs, risks, and benefits,” added study Co-Chair Ian D. Davis, Ph.D., of Monash University Eastern Health Clinical School, Victoria, Australia.

The study found that enzalutamide is more effective than the current standard of care using  bicalutamide, nilutamide, or flutamide, the comparison standard nonsteroidal antiandrogens used in the trial. However, enzalutamide can lead to different side effects.

The trial involved men with metastatic hormone-sensitive prostate cancer (yes, we said hormone sensitive) who were randomly assigned between March 2014 and March 2017 to receive an injection of a testosterone-suppressing medicine (such as goserelin, leuprolide, or degarelix) with either a 160-mg dose of enzalutamide daily or one of three standard other nonsteroidal antiandrogens: bicalutamide, nilutamide, or flutamide. 

Of the 1,125 men enrolled in the trial, 503 men received early doses of docetaxel, and 602 did not.

Men were followed for a median of 34 months. After three years, 80% of men with metastatic hormone-sensitive prostate cancer who received enzalutamide along with ADT, with or without early docetaxel, were alive, compared with 72% of men who received one of the other three nonsteroidal antiandrogens. 

Overall, there was a 33% decrease in the risk of death in men receiving enzalutamide compared to those who took another nonsteroidal antiandrogen.

On a sub-group analysis, of 596 men with a higher amount of disease on imaging scans, 71% taking enzalutamide were alive compared with 64% taking another nonsteroidal antiandrogen. Of 529 men with a low amount of disease on imaging scans, 90% taking enzalutamide were alive compared with 82% taking another nonsteroidal antiandrogen.

Among patients who received enzalutamide without docetaxel, 83% were alive, compared with 70% taking another nonsteroidal antiandrogen. At the time of the first analysis of the data, 64% of men were still taking enzalutamide, compared with 36% of men taking another nonsteroidal antiandrogen. 

Serious adverse events occurred in 42% of men taking enzalutamide compared with 34% of the men taking one of the other nonsteroidal antiandrogens 

It should be noted that a survival benefit is not seen with docetaxel in men with a low volume of disease, but that enzalutamide does improve survival in these men.

THE BOTTOM LINE

Health Canada has recently approved an expanded use for enzalutamide (Xtandi) so that it can now be prescribed to treat men with non-metastatic castration-resistant prostate cancer (nmCRPC).  This expanded label is in addition to the already existing indications for men with metastatic castrate resistant prostate cancer (mCRPC), making Xtandi a treatment option in Canada for men with both non-metastatic and metastatic castrate resistant prostate cancer.  

This new approval was granted based on results from the Phase 3 PROSPER trial which demonstrated that the use of Xtandi plus androgen deprivation therapy (ADT) significantly reduced the risk of developing metastasis or death compared to treatment with ADT alone in men with non-metastatic CRPC who were high-risk or experiencing a rapidly rising PSA level. 

A total of 99 randomized Canadian patients participated in the PROSPER trial, which had total participation of 1,401 patients. There were 14 trial sites in Canada, including locations in British Columbia, Alberta, Manitoba, Ontario, Quebec, and Nova Scotia. Data from the PROSPER study was presented at the 2018 Genitourinary Cancers Symposium (ASCO GU) in February and published in the New England Journal of Medicine in June.

"This approval is welcome news for physicians and patients alike," said Dr. Fred Saad, MD, FRCSC, Professor and Chief of Urology and Director of G-U Oncology at the University of Montreal Hospital Centres, and an investigator in the PROSPER trial.  "Reducing the risk of disease progression is an important treatment goal in patients with non-metastatic prostate cancer. With the PROSPER results, we can now use enzalutamide to treat men at an earlier stage in their disease."

Enzalutamide, Obat Oral Pertama Untuk Kanker Prostat yang Resisten

FDA telah menyetujui Aplikasi Obat Baru tambahan (sNDA) untuk enzalutamide (Xtandi) untuk pengobatan kanker prostat resisten non-metastasis (castration-resistant prostate cancer/CRPC), menurut siaran pers.

Dengan indikasi baru ini, enzalutamide adalah obat oral pertama yang disetujui FDA baik untuk CRPC non metastatik dan metastasis.

Persetujuan terbaru untuk enzalutamide, yang sebelumnya…

One of the most puzzling questions faced by men with advanced prostate cancer has to do with deciding which drug to take first, Zytiga (abiraterone) or Xtandi (enzalutamide)?  It is confusing because both are FDA approved for men who are chemotherapy-naïve with metastatic castrate resistant prostate cancer (mCRPC).

 Zytiga and Xtandi have not been evaluated with a head to head clinical trial, which is the only valid method, to know if there is a difference.  The current best information we have comes from a retrospective study (Terada) evaluating 198 men from Kyoto University Hospital in Kyoto, Japan and the Johns Hopkins Cancer Center in Baltimore, MD. 

The study compared both progression-free survival and overall survival (OS) for men who took Zytiga then moved on at disease progression to Xtandi to a group of men who started with Xtandi then, on disease progression moved on to Zytiga. 

They concluded that taking Zytiga first had a slight advantage over taking Xtandi as the first of the two treatments.  This conclusion was not statistically significant and did not take into account the differences in the prostate cancer that do exist from one man to another.

Câncer avançado: terapias combinadas?

Nicholas J. Vogelzang, em artigo recente, trata de casos de câncer da próstata que são diagnosticados quando o câncer já está adiantado, apresentado metástases. Segundo Vogelzang, esses casos correspondem a 3% do total de diagnosticados nos Estados Unidos. Desde a revolução do PSA foi possível identificar canceres assintomáticos e começar tratamentos meses, até mesmo anos, antes do primeiro…