Docetaxel Was Widely Used to Treat Metastatic Prostate Cancer before Conclusive Evidence Showed Its Superiority

The gist: The drug docetaxel was widely used to treat patients with metastatic prostate cancer before phase III clinical trials showed it was better than standard treatment. This is significant for a few reasons. First, it shows that many doctors are willing to prescribe promising drugs “off-label,” before the U.S. Food and Drug Administration (FDA) has approved them  for treating certain conditions. It also shows that a drug that is used for one type of cancer is more likely to be prescribed off-label for other types of cancer. Some are concerned that off-label prescriptions undermine the clinical trial process and put some patients at risk by giving them drugs that may not turn out to be better.

‘Docetaxel was being widely used by patients with metastatic prostate cancer before phase III evidence that it was more effective than standard-of-care for patients with castration-resistant prostate cancer, according to an analysis of Medicare claims from before and after the trial results and approval of docetaxel by the U.S. Food and Drug Administration. The uptake of new treatments, or diffusion, “prior to definitive evidence indicates the prevalence of off-label chemotherapy use,” wrote Unger et al in the Journal of the National Cancer Institute

“Rapid and widespread use of docetaxel was not observed among all study participants receiving chemotherapy for metastatic prostate cancer. Statistically significant docetaxel uptake (P < .01) was seen in patients older than 65 years of age, blacks, patients in lower income areas, and those who experienced poverty. This observation ‘presents opportunities to improve the uptake of proven new therapies in subpopulations,’ the authors wrote, adding that direct-to-consumer advertising ‘could be a useful tool.’

Another potential method cited for encouraging more rapid adoption of new treatments was ‘enhancing communication channels among physicians, especially between key opinion leaders and their colleagues,’ the authors noted. ‘One factor that has been repeatedly identified to increase adoption rates is attendance at scientific symposia, which serve as forums for disseminating information about new treatments.’ ”


Zytiga with Prednisone Improves Survival in Castration-Resistant Prostate Cancer Patients

The gist: Adding the drug abiraterone acetate (Zytiga) to treatment with prednisone helps patients with castration-resistant prostate cancer (CRPC) live longer. The treatment was tested in patients in a clinical trial. Patients in the trial were treated between April 2009 and June 2010. The treatment appeared to lengthen the amount of time that patients lived without their disease worsening. In 2011, these promising results convinced the U.S. Food and Drug Administration (FDA) to approve Zytiga for treating metastatic castration-resistant prostate cancer patients who had not yet received chemotherapy. Now, in final analysis of data from the trial, researchers have shown that Zytiga lengthens life for these patients.

“In the final analysis of overall survival in the COU-AA-302 trial, reported in The Lancet Oncology by Ryan et al, the addition of abiraterone acetate (Zytiga) to prednisone significantly prolonged survival in chemotherapy-naive patients with castration-resistant prostate cancer. Abiraterone had been approved for use in this setting on the basis of improved radiographic progression-free survival in COU-AA-302.

“In this double-blind trial, 1,088 asymptomatic or mildly symptomatic patients were randomly assigned between April 2009 and June 2010 to receive abiraterone at 1,000 mg once daily plus prednisone at 5 mg twice daily (n = 546) or prednisone plus placebo (n = 542). The coprimary endpoints were radiographic progression-free survival and overall survival…

“The investigators concluded: ‘In this randomised phase 3 trial with a median follow-up of more than 4 years, treatment with abiraterone acetate prolonged overall survival compared with prednisone alone by a margin that was both clinically and statistically significant. These results further support the favourable safety profile of abiraterone acetate in patients with chemotherapy-naive metastatic castration-resistant prostate cancer.’ ”


Enzalutamide Outperforms Bicalutamide in Trial for Metastatic Castration-Resistant Prostate Cancer

The gist: In a clinical trial with metastatic, castration-resistant prostate cancer (CRPC) patients, the drug enzalutamide outperformed bicaluatmide. Men who took enzalutamide had about 10 more months without their disease worsening than men who took bicalutamide. 

“Medivation, Inc. MDVN, -3.90% and Astellas Pharma Inc. today announced topline results from the Phase 2 TERRAIN trial comparing enzalutamide with bicalutamide in men with metastatic castration-resistant prostate cancer. The study achieved its primary endpoint demonstrating a statistically significant increase in progression-free survival (PFS) for enzalutamide compared to bicalutamide (Hazard Ratio = 0.44; 95% Confidence Interval, 0.34-0.57; p < 0.0001). Median PFS was 15.7 months in the enzalutamide group compared to 5.8 months in the bicalutamide group.

“The median time on treatment in TERRAIN was 11.7 months in the enzalutamide group versus 5.8 months in the bicalutamide group. Serious adverse events were reported in 31.1% of enzalutamide-treated patients and 23.3% of bicalutamide-treated patients. Grade 3 or higher cardiac adverse events were reported in 5.5% of enzalutamide-treated patients versus 2.1% of bicalutamide-treated patients. Two seizures were reported in the enzalutamide group and one in the bicalutamide group. The most common side effects occurring during treatment and more common in the enzalutamide-treated versus bicalutamide-treated patients included fatigue, hot flush, hypertension, diarrhea, weight decreased and pain in extremity.

” ‘The results of this study showed that enzalutamide provides a longer duration of disease control in the studied patient population compared to bicalutamide,’ said Neal Shore, MD, co-principal investigator of the TERRAIN study and Medical Director, Carolina Urologic Research Center. ‘This robust data set adds to an impressive and consistent body of data for enzalutamide across multiple studies and stages of prostate cancer.’ “


Phase III Trial of Drug Custirsen in Prostate Cancer Produces Positive Interim Results

The gist: A clinical trial is currently testing a drug called custirsen in men with metastatic, castration-resistant prostate cancer (CRPC). The patients are receiving custirsen along with the chemotherapy drug cabazitaxel. The trial recently underwent a “futility analysis” to ensure it could continue as planned. Final results will be announced later this year or in 2016.

“OncoGenex Pharmaceuticals, Inc. (OGXI) today announced that the AFFINITY trial is continuing as planned based upon completion of the interim futility analysis and the recommendation of the Independent Data Monitoring Committee (IDMC).

“The Phase 3 AFFINITY trial is designed to evaluate a survival benefit for custirsen in combination with second-line cabazitaxel chemotherapy in 635 men with metastatic castrate-resistant prostate cancer (CRPC). AFFINITY is being conducted at 95 global clinical trial sites and final survival results are expected to be announced in late 2015 or early 2016.

” ‘While the results remain blinded to OncoGenex, we are very pleased that the AFFINITY trial has passed this interim futility analysis and we remain confident in the potential value of custirsen in treating cancer, particularly in patients who have advancing disease despite previous treatments,’ said Scott Cormack, President and CEO of OncoGenex.”


Men Treated with Enzalutamide Experienced a 17-Month Delay in the Time to Initiation of Chemotherapy Compared to Placebo

The gist: Prostate cancer patients in the EU can now be treated with the drug enzalutamide (aka XTANDI). The European Commission approved the drug for adult men with metastatic castration-resistant prostate cancer (nCRPC) who have no symptoms or mild symptoms after failed treatment with androgen deprivation therapy, and who are not yet eligible for chemotherapy treatment. In a clinical trial with volunteer patients, enzalutamide gave men 17 extra months before chemotherapy was needed.

“Astellas Pharma Europe Ltd. today announced that the European Commission (EC) has granted a variation to amend the Marketing Authorisation for enzalutamide (trade name XTANDI).1 Enzalutamide is now approved in Europe for the treatment of adult men with metastatic castration-resistant prostate cancer (mCRPC) who are asymptomatic or mildly symptomatic after failure of androgen deprivation therapy in whom chemotherapy is not yet clinically indicated.1

“ ‘Enzalutamide provides a viable treatment option for a broad population of men with mCRPC, regardless of age, or their readiness for chemotherapy, which provides a meaningful period of time during which men have their disease controlled without the need for chemotherapy’, said Professor Bertrand Tombal, MD, PhD, Chairman of the Division of Urology and Professor of Physiology, Université Catholique de Louvain (UCL) and European Principal Investigator for PREVAIL. ‘The decision from the European Commission to approve enzalutamide, an effective and well tolerated alternative to chemotherapy, is a very important milestone for men with prostate cancer that has advanced.’

“The Marketing Authorisation approval is based on results from the pivotal phase III PREVAIL study which demonstrate that enzalutamide improves outcomes for men with advanced prostate cancer who have not received chemotherapy.2″


Future of Exelixis Cancer Drug Dims Further With Second Failed Prostate Cancer Study

The gist: A drug called cabozantinib doesn’t do any better than a steroid treatment when it comes to relieving bone pain in men with metastatic castration-resistant prostate cancer. That was the conclusion of a recent clinical trial that tested the drug in volunteer patients. The trial enrolled men who were suffering from moderate to severe pain despite optimized narcotic medication, and whose cancer had worsened after treatment with docetaxel as well as abiraterone and/or enzalutamide. Some of the men in the trial were treated with cabozantinib, and some with the steroid treatment mitoxantrone/prednisone.

“Exelixis (EXEL) announced Monday that treatment with cabozantinib failed to alleviate bone pain compared to a steroid control in men with advanced, metastatic prostate cancer. A negative outcome from the so-called COMET-2 prostate cancer study of cabozantinib was widely expected given the previously announced failure of the COMET-1 study in September. Still, Exelixis shares fell another 10% to $1.49 — an all-time low — on heightened concerns that ongoing cabozantinib studies in kidney and liver cancer may also prove disappointing.

“A few years ago, there was much optimism for cabozantinib based on phase II data showing the drug cleared bone lesions and reduced pain in advanced prostate cancer patients. Cancer that metastasizes, or spreads, to bones is a serious complication leading to fractures, increased pain and eventual death. While many cancer drugs can shrink or eliminate tumors in soft tissue, few if any had ever demonstrated an ability to clear up bone metastases.

“All too often, promising results from phase II studies don’t pan out when larger, confirmatory phase III studies are conducted. That’s exactly what happened to Exelixis. In the COMET-2 study, 15% of prostate cancer patients with moderate to severe bone pain despite use of narcotics responded to treatment with cabozantinib compared to 17% of patients treated with steroids. Clearly, this is not the results Exelixis had in mind three years ago when reporting on the phase II bone lesion/bone pain data in the phase II study.”


SOTIO Initiates US Part of VIABLE, a Global Phase III Clinical Trial for Prostate Cancer Immunotherapy Treatment with DCVAC/PCa

The gist: Researchers are testing a potential new prostate cancer treatment that boosts the immune system to fight prostate cancer. The immunotherapy is called DCVAC/PCa. It is made from a patient’s own immune system cells. It is being tested in a clinical trial in volunteer patients with metastatic castration‐resistant prostate cancer who have not yet received chemotherapy. Patients interested in enrolling can learn more at the trial website.

“The first US patient was enrolled into this Phase III global study in Rockville, MD. SOTIO is targeting to enroll around 250 US patients, collaborating with physicians from more than 80 US medical centers. Initial patients were also recently enrolled into the study in Italy, UK, the Netherlands and Slovakia. The VIABLE study plans to recruit patients through cooperation with medical centers in the United States, Canada and 25 European countries. SOTIO’s aim is to enroll approximately 1,170 prostate cancer patients globally. The first patient was enrolled into the VIABLE study in Hungary in May 2014.

“Niels Borgstein, Chief Medical Officer of SOTIO US commented: ‘Commencing the VIABLE study in the US is a crucial next step in our global clinical strategy to help develop a novel immunotherapy for the treatment of prostate cancer patients.’

“Professor Radek Špíšek, Chief Scientific Officer of SOTIO explained: ‘We believe that in order to be successful in treating advanced stages of prostate cancer it is essential to understand if cancer immunotherapy should be combined with existing treatment modalities, such as chemotherapy. In accordance with this strategy, we have designed a chemo-immunotherapy clinical trial that explores the combination of both standard of care chemotherapy including a novel dendritic cell based immunotherapy known as DCVAC/PCa.’ “


Galeterone Shows Activity in a Variant Form of Castration-Resistant Prostate Cancer

The gist: A drug called galeterone might help lower PSA levels in certain men with castration-resistant prostate cancer (CRPC). A clinical trial recently tested the treatment in volunteer patients.

“Results from a trial of the anti-cancer drug galeterone show that it is successful in lowering prostate-specific antigen (PSA) levels in men with a form of prostate cancer that is resistant to treatment with hormone therapy (castration-resistant prostate cancer or CRPC).

“Associate professor Mary-Ellen Taplin, of the Dana-Farber Cancer Institute, Boston, USA, will tell the 26th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics in Barcelona, Spain, today (Wednesday) that galeterone was well tolerated by patients in the ARMOR2 trial, and also lowered PSA levels in a subset of men with CRPC that was resistant to other drugs that target the cancer, such as enzalutamide and abiraterone.

” ‘Recent data have shown that a variant of the androgen receptor called AR-V7, found in tumour cells circulating in the blood of patients with metastatic CRPC, predicted resistance to treatment with enzalutamide and abiraterone,’ she will say. ‘Indeed, we believe AR-V7 and other, related variants are a mechanism of resistance in this disease and patients who have them may have a poorer prognosis.’ ”


Drugs Home in on Bone Metastases in Prostate Cancer


Bone metastases are common in patients with metastatic castration-resistant prostate cancer (CRPC). They are associated with increased risk of death due to a number of complications such as bone fractures, compression of the spinal cord, and pain. Radiation of the affected bone sites is used as a palliative measure to relieve pain. The U.S. Food and Drug Administration (FDA) has also approved certain drugs for treatment of bone metastases in CRPC including the following: Continue reading…