Advanced Prostate Cancer Newsletter

Archive for Alpharadin (radium-223)

Officials from the National Institute for Health and Care Excellence (Nice) have made a preliminary decision not to recommend covering the drug radium-223 dichloride (Xofigo) for use for men with prostate cancer that has spread to the bone.

This latest draft guidance from Nice states that Bayer has not provided information on how Xofigo performs in contrast to other currently available drugs for use in the health service in England and Wales.

Malecare is urging that Bayer provide the required information prior to NICE making their final determination so that men in need will not be denied this safe and effective drug.  We know that Xofigo can extend survival by 3.6 months and improve the quality of life with only minor side effects.

Men qualifying for Xofigo are already have very progressed disease with multiple bone metastases.  It is nothing short of criminal that they be denied this proven treatment, especially when they are in a position where there are so little alternatives and often suffering with significant pain.

According to Nice chief executive Sir Andrew Dillon: “Clinical specialists told the committee that radium-223 (Xofigo) would be used as an alternative treatment option to docetaxel as an initial treatment, and abiraterone as a second-line treatment when the disease has progressed. However, Bayer did not to provide the committee with any data on how well radium-223 works compared to docetaxel or abiraterone or, only comparing it to a placebo.”  I find this confusing, as Xofigo should not be used as an alternative to docetaxel or abiraterone, but as an additional treatment.

Joel T Nowak, M.A., M.S.W.

Most people don’t know of the great work that has been carried out by group of determined advocates on behalf of men with advanced prostate cancer. These hard working advocates, who reach out across different advocacy groups (Malecare, PCRI , PHEN, PAACT and USTOO) have formed a committee they call the The Early/Expanded Access Committee (EAP).

The EAP meet with pharmaceutical companies on a regular basis to encourage them to make their promising drugs and treatments available to individuals before they have formally received FDA approval. They do this by the way of a vehicle they call the Early Access Program (EAP). The EAP identify drugs that are designed to treat men with advanced prostate cancer, that during their phase III trials clearly demonstrate great safety profiles and excellent efficacy, but have not yet received formal FDA approval.

As mentioned, the EAP meet with pharmaceutical company representatives to open the door for drug access, they help identify doctors who are willing to use these drugs, under the FDA guidance as a EAP clinical trial so that men don’t need to wait around for formal FDA approval. Not only does this program offer early access, it provides the pharmaceutical company and the FDA with a wealth of additional material about the safety and efficacy of the treatment which can be factored into their ultimate decision about approval.

THE EAP provides new hope for families around the world, they provide a paradigm that will be used in prostate and all other cancers in a short period of time.

The EAP has had three major successes to date, abiraterone, enzalutiamide and radium 223. Each of these drugs was made available to men in need prior to their receiving approval from the FDA, with the blessing of the FDA. The EAP recently performed an analysis of their impact with each of these drugs.

Jan Manarite (PCRI) who is an active member of the EAP, for the EAP “After the Expanded Access Committee had some success promoting and encouraging Expanded Access with our 3rd drug (radium 223), I always wanted to get the numbers, just to see what we did. Here’s what it looks like. I continue to think that small groups with simple goals can do big things….”

————————————————————————————————————————————

EAP Numbers – Patients Served

abiraterone *-    432 men received the treatment under the EAP from 33 states and the District of Columbia from Oct 2010 – Apr 2011

enzalutamide ** 508 men received the treatment under the EAP from  25 states and 6 Canadian Provinces from May 2012 – Aug 2012

radium 223***   200 men received the treatment under the EAP from 18 states from Jan 2012 – May 2013

TOTAL MEN SERVED –     1140

Sources:

* Joanne M. Vanak, RN, MSN, Senior Director, Scientific Advocacy, Janssen – 1/16/14

** Nahla Hasabou, MD, CCRP, Medical Monitor, Oncology Medical Science, Astellas – 9/3/13

*** Svetlana Babajanyan MS MD, Medical Director, Bayer HealthCare Pharmaceuticals Inc. – 8/5/13

This program is a roaring success fostered by the hard work from a number of different prostate cancer advocacy organizations as well as a number of dedicated physicians and researchers.  One also needs to acknowledge the supportive role that the FDA has decided to take in encouraging these Early Access Trials.

Joel T. Nowak, M.A., M.S.W.

Men with metastatic castration-resistant prostate cancer (mCRPC) in Québec, Canada now have access to Zytiga (abiraterone acetate) prior to having chemotherapy.

Effective February 3, 2014, the province has added ZYTIGA to the public drug formulary for the treatment of mCRPC in men who are asymptomatic or mildly symptomatic after failure of androgen deprivation therapy (ADT).

In July 2011, ZYTIGA was approved by Health Canada for the treatment of men with mCRPC who had received prior chemotherapy containing docetaxel after failure of ADT. Health Canada approved a second indication for ZYTIGA in May 2013 for the treatment of men with mCRPC who are asymptomatic or mildly symptomatic after failure of ADT.

Québec joins British Columbia as the second province to add ZYTIGA to its public formulary for men with mCRPC who are asymptomatic or mildly symptomatic after failure of ADT.

On the European front men with metastatic prostate cancer can now get radium-223 as it has now been approved by NHS England.

In April 2013 NHS took responsibility for cancer drugs and on February 2014,following a review of data by the chemotherapy clinical reference group, radium-233 (Xofigo) was added to their approved list.

In a statement, health secretary Jeremy Hunt said: “Better access to effective medicine is a priority for the Government, and we are delighted that these new drugs will mean more patients will join over 38,000 cancer sufferers who have already benefited from the fund.”

Prostate cancer drugs become increasingly available for men all over the world, but not at a rate that still sees many more men than necessary continue to suffer and die when there are proven drugs and treatments languish waiting for redundant reviews.

Perhaps our remarkable politicians and government administrators could go back to the thinking well and fix the system. Perhaps they should consider an interim automatic approvals for a drug once they have been approved somewhere else by one of their large and respected counterparts in the world. They could still perform their own review and come to their own conclusion, but while we wait these vital treatments will be available to their own citizens. This is a simple and safe approval system that should not threaten each county’s independence and speed the delivery of drugs to those in significant need.

Joel T. Nowak, M.A.S., M.A.

Now that Radium-223 Dichloride (Xofigo) has been approved by the FDA for use in men with castrate resistant prostate cancer with bone metastases we will begin to see the actual treatments happening. The next question in the process that will arise is whether or not it is safe and effective to re-treat an individual with additional rounds of the drug once it has failed.

In many of the other treatments we use for advanced prostate cancer we have found that it is possible to go back after a treatment failure and re-institute the treatment and see a positive result. Will this work with Xofigo and given that it is radiation is it safe to retreat a man?

To begin to answer these questions there will be a new phase 1-2 clinical trial to evaluate the potential of Xofigo retreatment. The trial whch is scheduled to begin in November (this month) still has not formerly begun.

It is expected to enroll 40 men who meet the following criteria:
1. The man has already received the full 6 treatments of Xofigo.
2. The man has finished the initial treatment cycle (6 injections) more than 30 days ago.
3. The man has no enlarged lymph nodes greater than 6 cm.
4. The man has no visceral metastases (lung, liver, soft tissue) greater than 1 cm.
5. The man has no brain metastases.
6. The man has not had any chemotherapy since the last Xofigo treatment cycle.

The trial will have as its primary outcomes (results):
• Evaluating the number of men with either treatment-related AEs (adverse events) or SAEs (serious adverse events) [ Time Frame: Up to 7 months ] [ Designated as safety issue: Yes ]
• NEvaluating the number of participants with Radium-223 dichloride-related SAEs in the active follow-up period [ Time Frame: Up to 2 years after last treatment ] [ Designated as safety issue: Yes ]
• Any changes in complete blood count [ Time Frame: Up to 2.5 years ] [ Designated as safety issue: Yes ]
• The total number of participants who discontinue Radium-223 dichloride treatment due to treatment emergent AEs or death [ Time Frame: Up to 7 months ] [ Designated as safety issue: Yes ]

To read more about the trial go to: Xofigo Re-treat Trial
ClinicalTrials.gov Identifier: NCT01934790

If you believe that you are qualified (having had Xofigo over 30 days prior) and would be interested in participating you should contact:
Dr. Oliver Sartor, Tulane University
Contact: Patrick Cotogno, pcotogno@tulane.edu, (504) 988-6542

Joel T. Nowak, M.A., M.S.W.

We are in the fortunate position because the treatment of men with metastatic castration-resistant prostate cancer (mCRPC) continues to evolve as new agents with the ability to extend survival gain FDA approval. The most recently FDA approved treatment, the alpha emitting radiopharmaceutical radium-223 (Xofigo) was approved for men with bone metastatic prostate cancer.

Most other of the newly approved treatments was designed with the initial intention of providing an increase in overall survival (OS), but Xofigo is different.  Like the other already approved  radio emitting agents Strontium and Samarium which are beta-emitting agents Xofigo was initially explored solely as a palliative treatment option.  However, the investigation quickly changed once it was discovered in very early trials that Xofigo, not like the other  agents, also improved survival in addition to providing palliative benefit.

Besides a survival advantage, Xofigo also provides a great measure of superiority over the beta-emitting agents (which irradiate a large area including bone marrow) because as a alpha-emitting agent it only irradiates a very localized area.  Since the vast majority of prostate cancer bone metastasis are in the bone and not in the marrow, Xofigo is very affective in treating these mets while not damaging the bone marrow, a significant advantage over the beta emitting treatments.

Xofigo is a game changer with a huge potential for a major role in our treatment protocol.

Joel T. Nowak, M.A., M.S.W.