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…

Radium-223 Dichloride Effective in CRPC, Regardless of Prior Docetaxel

The gist: The drug Xofigo (aka radium-223 dichloride) is often used to treat bone metastases in patients with castration-resistant prostate cancer. New research results show that it is safe and effective for these patients whether or not they have previously been treated with the chemotherapy drug docetaxel.

“Radium Ra 223 dichloride appeared safe and effective in patients with castration-resistant prostate cancer and symptomatic bone metastases regardless of whether they received prior docetaxel, according to a subgroup analysis from a randomized phase 3 trial.

“Results of the ALSYMPCA showed radium Ra 223 dichloride [radium-223 (Xofigo, Bayer)], a targeted alpha-emitter, extended OS compared with placebo in patients with castration-resistant prostate cancer and symptomatic bone metastases. The agent also appeared well tolerated.

“Researchers established prior docetaxel treatment as a trial stratification factor.

“In the prespecified subgroup analysis, researchers sought to assess the effect of prior docetaxel treatment on efficacy and safety outcomes.”

Sequencing Radium-223 and Docetaxel in Prostate Cancer

The gist: Scientists have found that the drug Xofigo (aka radium Ra223 dichloride) is “equally effective whether or not the patient has previously received chemotherapy with docetaxel.” Xofigo us used for men with metastatic castration-resistant prostate cancer (mCRPC).

“The novel radiopharmaceutical for prostate cancer, radium Ra223 dichloride (Xofigo), is equally effective whether or not the patient has previously received chemotherapy with docetaxel, a new analysis concludes.

“The product was approved last year for the treatment of metastatic castration-resistant prostate cancer (mCRPC) on the basis of results from the ALSYMCA study.

“Now, the ALSYMCA investigators report a prespecified analysis that shows that radium-223 is effective in these patients, regardless of previous docetaxel use. The report was published online October 17 in the Lancet Oncology.

“In an accompanying comment, Robert B. Den, MD, and W. Kevin Kelly, DO, from the Departments of Radiation and Medical Oncology, respectively, at Thomas Jefferson University in Philadelphia, say the new analysis shows that ‘men who have received previous docetaxel chemotherapy can be given radium-223 safely and its efficacy will be similar to patients who have not received previous docetaxel treatment.’

“But they also advocate caution. ‘The oncology community needs to proceed cautiously, since the ALSYMPCA trial was not able to identify the optimum sequence of administration of docetaxel and radium-233. Additionally, the trial was designed before the approval of enzalutamide and abiraterone acetate, so the clinical benefit of concomitant or sequential use of radium-223 with these drugs is unknown. Perhaps most intriguing would be the opportunity to integrate immunotherapy.’ “

Abiraterone Acetate/Prednisone in Metastatic Castration-Resistant Prostate Cancer: Final Analysis of Early-Access Protocol Study

The gist: In 2012, the U.S. Food and Drug Administration (FDA) approved a drug called Zytiga for the treatment of metastatic castration-resistant prostate cancer. It is prescribed along with the drug prednisone. Before the FDA’s approval, the Zytiga/prednisone combination was being tested in patients in a clinical trial. The trial was an “early-access” trial, meaning that it gave patients access to a very promising treatment that had not yet been approved. All patients involved had metastatic castration-resistant prostate cancer that had worsened after chemotherapy. Recently reported results from the trial showed no new safety concerns for the treatment.

“Abiraterone acetate (Zytiga) is approved for use in combination with prednisone in the treatment of metastatic castration-resistant prostate cancer. As reported by Sternberg et al in The Lancet Oncology, results of an open-label, early-access protocol trial initiated prior to approval indicated no new safety signals with abiraterone acetate plus prednisone given after progression on chemotherapy…

“The study, conducted in 23 countries, included 2,314 patients with metastatic castration-resistant prostate cancer progressing after taxane chemotherapy enrolled between November 2010 and September 2013. Patients received abiraterone acetate 1,000 mg/day and prednisone 5 mg twice a day in 28-day cycles until disease progression, development of sustained side effects, or approval and availability of abiraterone acetate in the country of residence…

“The investigators concluded: ‘No new safety signals or unexpected adverse events were found in this early-access protocol trial to assess abiraterone acetate for patients with metastatic castration-resistant prostate cancer who progressed after chemotherapy. Future work is needed to ascertain the most effective regimen of abiraterone acetate to optimise patients’ outcomes.’ ”

Bayer and Orion Initiate Phase III Trial of Novel Prostate Cancer Agent ODM-201 in Men with High-Risk Non-Metastatic Castration-Resistant Prostate Cancer

The gist: A new clinical trial—a research study with volunteer patients—is testing a new prostate cancer drug. The drug is called ODM-201 and is being given to participating patients in Finland. Specifically, the drug is being tested in”men with castration-resistant prostate cancer (CRPC) who have rising Prostate-Specific Antigen (PSA) levels and no detectable metastases.”

“Bayer HealthCare and Orion Corporation, a pharmaceutical company based in Espoo, Finland, have begun to enroll patients in a Phase III trial with ODM-201, an investigational novel oral androgen receptor (AR) inhibitor in clinical development for the treatment of patients with prostate cancer. The study, called ARAMIS, evaluates ODM-201 in men with castration-resistant prostate cancer (CRPC) who have rising Prostate-Specific Antigen (PSA) levels and no detectable metastases. The trial is designed to determine the effects of the treatment on metastasis-free survival (MFS).

“ ‘The field of treatment options for prostate cancer patients is evolving rapidly. However, once prostate cancer becomes resistant to conventional anti-hormonal therapy, many patients will eventually develop metastatic disease,’ said Dr. Joerg Moeller, Member of the Bayer HealthCare Executive Committee and Head of Global Development. ‘The initiation of a Phase III clinical trial for ODM-201 marks the starting point for a potential new treatment option for patients whose cancer has not yet spread and is an important milestone for Bayer in our ongoing effort to meet the unmet needs of people affected by cancer.’ ”

UPDATE 1-U.S. FDA Approves Expanded Use of Medivation Prostate Cancer Drug

The gist: When a drug company creates a new cancer treatment, the treatment must be approved by the U.S. Food and Drug Administration (FDA) before doctors in the U.S. can prescribe it. An FDA approval for a new drug usually specifies the particular kinds of patients who are allowed to be treated. In 2012, drug called Xtandi was FDA-approved for treating people with metastatic castration-resistant prostate cancer (mCRPC) who have been previously but unsuccessfully treated with chemotherapy. Now, the FDA has also approved Xtandi for people with mCRPC who have not yet tried chemotherapy.

“U.S. health regulators approved the use of Medivation Inc’s and Astellas Pharma Inc’s advanced prostate cancer drug Xtandi in men who have not yet received chemotherapy, the companies said on Wednesday, significantly expanding the potential patient population for the oral medicine.

“The expanded Food and Drug Administration approval will also enable the drug to better compete with Johnson & Johnson’s Zytiga. The approval triggers $90 million in milestone payments to Medivation by Japan’s Astellas under a collaboration agreement.

“Xtandi, known chemically as enzalutamide, originally gained U.S. approval in 2012 for use in patients with castration-resistant prostate cancer that has spread beyond the prostate only after they had first received chemotherapy treatment.

” ‘The average duration of treatment should double and the addressable patient population triple in the pre-chemo setting,’ Sanford Bernstein analyst Geoffrey Porges said in a research note earlier this week.”