Cancer Decisions - Free Newsletter

INTELLECTUAL INDEPENDENCE

Here at the Moss Reports we have always believed passionately that freedom from commercial influence is one of the most precious guarantees of objectivity. This is the reason why we have steadfastly refused to accept advertising or sponsorship of any sort. By doggedly maintaining our independence in this way we have been able to continue bringing our readers the sort of unbiased information that is increasingly hard to find elsewhere.

Over the past 30 years I have written and published extensively on the subject of cancer and its treatment. I have compiled a comprehensive series of more than 200 individual reports on different cancer diagnoses - The Moss Reports - each of which examines both the standard treatment options that are likely to be offered for a particular cancer diagnosis, and the possible alternative and complementary approaches to that disease. These reports also contain extensive dietary and nutritional information for those who are actively dealing with cancer as well as for those who are recovering from treatment and hoping to prevent recurrence.

Typical of the comments we receive from those who have purchased a Moss Report is the following:

"For the past two and a half years I have battled breast cancer by natural and alternative methods, having done an in-depth research of all the options. Dr Moss' support and the knowledge he has amassed have been an endless source of comfort. When I have reached different stages of my illness and I have found myself at a crossroads, I have called upon the advice of Dr. Ralph Moss as one of the only sources of truly objective information. Without his input, I would have been lost. He has done more for me than many of the private doctors that I have consulted and I certainly have felt a deep feeling of care on a personal basis. That has been invaluable. I thank him from the bottom of my heart." - C.H.A.

If you would like to order a Moss Report for yourself or someone you love, you can do so easily and securely from our website, www.cancerdecisions.com, or by calling 1-800-980-1234 (814-238-3367 from outside the US).

PHONE CONSULTATIONS

To those who have already purchased a Moss Report I also offer phone consultations. A phone consultation can be enormously helpful in drawing up an effective treatment strategy and getting one's options clearly prioritized. A recent phone consultation client wrote:

"The private phone consultation was extremely helpful. Ralph Moss has a wonderful ability to convey information in a clear and easy to understand way. His explanations of why and how various treatments work made arriving at a decision on which treatment to use for my advanced condition less difficult. Dr. Moss is an excellent and compassionate listener. I feel like he is someone I can turn to for help in assessing my treatments and my progress. Many thanks." - D.B.

To schedule an appointment for a phone consultation, please call 1-800-980-1234 (814-238-3367 from outside the US), or send an email to Jacquie@cancerdecisions.com.

We look forward to helping you.

NEW CANCER DECISIONS® REPORTS

Scroll to the end of the newsletter for information on our useful Cancer Decisions® reports.

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AGAIN AVASTIN

Two months ago, the Oncology Drugs Advisory Committee (ODAC) ruled 5-4 that the Food and Drug Administration (FDA) should not approve the drug Avastin (bevacizumab) as a treatment for advanced breast cancer. (Currently, Avastin is only approved for use in patients with colorectal cancer.) The committee's reason for recommending against approval for use in breast cancer was that Avastin had not been proven to convey significant patient advantage in terms of either improved overall survival or quality of life.

To read our December, 2007 newsletter on the ODAC decision, please click here or go to:
http://www.cancerdecisions.com/121607.html

As a result of our December newsletter on this decision, many of our readers wrote to urge FDA officials to uphold the advisory board's decision.

Since December, executives of the California-based biotech firm Genentech (which manufactures Avastin), and its major stockholder, Roche, have been working and lobbying hard to overcome this FDA hurdle. This week they finally revealed their strategy and, unless there is an upsurge of objections from medical consumers, they may well get approval of the drug by FDA's February 23rd decision-making deadline.

On Tuesday, February 12, Genentech issued a statement on the so-called AVADO study, which is being conducted by Roche. The study was designed to compare outcomes in 736 patients with advanced breast cancer, all of whom received the standard chemotherapy drug docetaxel (Taxotere®), but half of whom also received Avastin.

"Genentech believes that the results of the AVADO study provide confirmation of Avastin's efficacy and safety in this patient population," the company said in its statement.

On what basis did Genentech make this confident assertion? What were the actual results of the study? Apparently nobody except a handful of company insiders and a few individuals at FDA know, since all the company was prepared to release publicly was a very general statement claiming that Avastin had "met its primary endpoint of prolonging progression-free survival (PFS) in patients who had not received prior chemotherapy for their locally recurrent or metastatic HER2-negative breast cancer. No new safety signals related to Avastin were observed. These data will be submitted for presentation at an upcoming medical meeting."

Attentive readers know that progression-free survival (PFS) and overall survival are not the same thing. Progression-free survival refers to the length of time a patient survives after treatment with no sign that the disease is advancing. By contrast, overall survival (OS) refers to the percentage of people in a study or treatment group who are alive for a given period of time after diagnosis or treatment.

The difference between these two measures is not trivial. PFS is by no means always synonymous with increased survival. Neither is progression free survival easy to measure objectively. As both FDA staff and ODAC members pointed out at the December meeting, it is difficult to gauge precisely when a cancer starts to progress, or worsen. Although achieving a period of stabilization or remission sounds like a worthwhile objective, if the patient does not live any longer as a result of this interlude its benefit is, to say the least, questionable.

In other words, a drug may change the shape of the patients' survival curve, but not alter the ultimate outcome. Treated patients may die on average at the same time as those who were not treated; sometimes they may even die sooner. So what has one actually accomplished with the intervention? Advocates of chemotherapy are apt to say that at least chemotherapy may improve patients' quality of life by increasing the period of time in which they are in remission. Remission is, they say, a psychological benefit. But that assumption is debatable, since patients who believe their disease is being controlled can feel an even greater sense of loss and disappointment when the disease again progresses than do those without any illusions about being cured of the disease. Disease-free survival in any case does not seem like sufficient reason to approve a new indication for a drug.

Genentech and Roche indicated that they would release the actual AVADO data at a future scientific meeting. They did not say whether the data would demonstrate an improvement in overall survival. Overall survival was considered one of the "secondary endpoints" in the AVADO study. But it is unclear if FDA has been provided with such data. Neither they, nor the company, have made such data available to outside scientists or to the concerned public.

Barbara Brenner, executive director of Breast Cancer Action, has demanded the full data from the company. "We are quite disturbed that this uninformative press release seems timed to coincide with the imminent decision by the FDA on the currently pending sBLA [supplemental Biologics License Application, ed.] for Avastin in the metastatic breast cancer setting," she wrote both Richard Pazdur, MD, of the FDA and David Shenkein, MD, of Genentech on Feb. 12, 2008.

Brenner also demanded release of so-called Phase IV data on Avastin's actual performance in clinical trials with colorectal cancer patients. (Phase IV studies are post-marketing reports on the actual safety and effectiveness of drugs as they are used in the real clinical setting. Such studies are often requested by FDA as a condition of drug approval, but are rarely carried out or published by drug companies.)

"We understand that Genentech is engaged in a thorough Phase IV trial of Avastin in the colorectal cancer setting," Brenner wrote. "If Avastin is approved for breast cancer based on information other than overall survival or improved quality of life, the FDA should require prompt and thorough Phase IV review as a condition of approval."

Misleading Media

Articles in the media have on the whole given the impression that Genentech has clinched the case for Avastin's efficacy, and that approval would seem to be just a matter of time. The New York Times, which often is skeptical of drug company claims, threw caution to the wind in this instance with its headline: "In Second Trial, Avastin Is Found Effective in Treating Breast Cancer" (New York Times, 2/13/08). This implies that drug company claims in press releases are the same as facts established by independent scientists in peer-reviewed studies.

Many other news sources made the same error. Reuters, for example, led with "Genentech's Avastin Meets Breast Cancer Study Goal," and the Wall St. Journal proclaimed: "Avastin With Chemotherapy Is Effective in Cancer Trial."

Huge amounts of money hang in the balance. Avastin, which costs patients and their insurers $4,400 per month, last year generated $2.3 billion in the US alone. Sales are projected to rise to $2.7 billion by 2009. The breast cancer market might be worth an equal or even greater amount, since there are more new cases of breast cancer in the US each year (181,000) than of colorectal cancer (154,000).

When ODAC recommended against extending the indication for Avastin last December, Genentech's stock fell about $10 per share. This meant an instant loss of around $10 billion for the company. It has recovered a bit since then, and on the announcement of the AVADO study, its shares rose 2.4 percent, to $71.60. According to J.P. Morgan analyst Geoffrey Meacham, there is now a 50-50 chance that FDA will approve Avastin for breast cancer. "The key question," said Meacham, "is whether the FDA will want better results on the drug's ability to improve the overall survival rate of patients. That data will be more difficult and time-consuming to produce than data on how long patients survive without the condition progressing" (AP, 2/13/08).

On the other hand, according to Michael Aberman, an analyst with Credit Suisse, without survival data the new trial would not increase the chance for Avastin's approval this month (Pollack 2/13/08). As Andrew Pollack wrote in the Times, "The decision is being closely watched as a barometer of the agency's standards toward approving new cancer drugs or expanding uses of current medications. It is possible the F.D.A. will delay the decision past February so it can consider the new data."

I once again urge readers to email FDA Commissioner Andrew von Eschenbach, MD, and Richard Pazdur, MD, director of FDA's office of oncology drug products, with their opinions on this matter. Consumer input could be crucial, especially at this critical juncture.

What I will convey to them, in my own letter, is that FDA should NOT approve Avastin for breast cancer until and unless there is impartial scientific proof that the drug actually extends women's overall survival.

Their email addresses are as follows:

andrew.voneschenbach@fda.hhs.gov

richard.pazdur@fda.hhs.gov

Letters by concerned citizens are, in my opinion, the main thing that is preventing FDA from yielding to drug industry pressure. They could influence FDA to put the needs of cancer patients above those of the drug companies, and only approve drugs that actually prolong lives.

--Ralph W. Moss, Ph.D.

DISCLOSURE: RWM is a member of the Scientific Advisory Board of the non-profit organization, Breast Cancer Action.

CANCER DECISIONS® REPORTS

Our Cancer Decisions® reports are designed to address specific treatment-related decisions in a number of different cancers.

Radiation And The Treatment Of Breast Cancer, for example, reviews the role of radiation in breast cancer and offers a thorough and thought-provoking analysis of its risks and benefits. Women weighing decisions about radiation will find it an invaluable guide. Among the topics covered are:

Understanding the risk of breast cancer recurrence
The use of radiation in different stages of breast cancer
The role of individual tumor characteristics in weighing risk
Breast conserving therapy (lumpectomy plus radiation)
Types of recurrence and their differing significance
Risks of radiation versus benefits
Evidence from major clinical trials concerning effectiveness
Concurrent chemotherapy and radiation
Advances in delivery of radiation treatment: new choices

Reviewing the report, Michael Janson, MD, has written:

"Dr. Moss is an excellent writer and he is thorough and unbiased in his evaluation of the science. His monograph is well-worth reading, and it will be helpful to breast-cancer patients and their families in their difficult decision-making process."

You can download a copy of this report directly from our Web site by clicking here:
https://webssl.cancerdecisions.com/list/optin.php?form_id=28

Other downloadable reports include Do Antioxidants Interfere With Cancer Treatment? – a detailed examination and rebuttal of the arguments that are often leveled against the use of antioxidants by cancer patients undergoing chemotherapy and radiation.

This report was very favorably received by prominent clinicians and researchers. For example:

"An excellent article that clearly brings into perspective the issues raised."
-Kenneth A. Conklin, MD, PhD, University of California, Los Angeles

"Excellent and timely."
-Jeanne Drisko, MD, University of Kansas Medical Center

You can purchase a copy of this report by clicking here or going to:
https://webssl.cancerdecisions.com/list/optin.php?form_id=29

References:

Genentech: Avado Phase III study of Avastin for breast cancer. CNNMoney.com – San Francisco, Feb. 12, 2008:
http://money.cnn.com/news/newsfeeds/articles/newstex/AFX-0013-22970164.htm

Genentech’s Avastin meets breast cancer study goal. By Bill Berkrot New York (Reuters) Feb. 13, 2008:
http://uk.reuters.com/article/healthNews/idUKN1226889020080213?feedType=RSS&feedName=
healthNews

Genentech: Avastin Breast Cancer Study Meets Goal. TheStreet.com. Feb. 12, 2008:
http://www.thestreet.com/s/genentech-avastin-breast-cancer-study-meets-goal/newsanalysis/
biotech/10403199.html?puc=_googlen?cm_ven=GOOGLEN&cm_cat=FREE&cm_ite=NA

Genentech Drug Meets Breast Cancer Goal, Houston Chronicle, Feb. 12, 2008:
http://www.chron.com/disp/story.mpl/ap/fn/5535917.html

Genetech’s press release on Avastin:
http://www.gene.com/gene/news/press-releases/display.do?method=detail&id=11007

JP Morgan Expects Eventual Avastin OK, Houston Chronicle, Feb. 12, 2008.

Pollack, Andrew. In Second Trial, Avastin Is Found Effective in Treating Breast Cancer, New York Times, Feb. 12, 2008.

Shwiff, Kathy. Avastin With Chemotherapy Is Effective in Cancer Trial. Wall Street Journal, Feb. 13, 2008.

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IMPORTANT DISCLAIMER

The news and other items in this newsletter are intended for informational purposes only. Nothing in this newsletter is intended to be a substitute for professional medical advice.