Barbara Brenner, Former Executive Director

Today is day 2 at the 30th SABCS meeting, and I’m thinking about what BCA should be doing at this meeting in the future. What is valuable to our constituency and what advances our mission? Since very few of the studies presented her have any meaning to patients now, it seems that our time might be best spent in San Antonio:

  • meeting  and strategizing with other breast cancer advocates and with scientists and researchers
  • doing outreach through our presence at a booth
  • training advocates to ask the hard questions that need to be answered in the interest of patients

Heard in the halls

One of the things I heard yesterday from Richard Peto, at the end of his presentation on the world wide overview of adjuvant treatment, was that “it’s a good time to be a statistician.” While that’s very nice for Dr. Peto, I wonder whether it’s also a good time to be a breast cancer patient (not that there is ever a good time to have breast cancer). Certainly there are more treatments available, and more reports on how treatments are working. Is this just more confusing for patients struggling to make treatment decisions? Should you have to be a statistician to understand what treatments might be best for you?

Now available for patients with brain metastases

A new website has been launched focused on brain metastases in breast cancer—www.brainmetsbc.org. The mission of the website is described as offering “women with metastatic breast cancer and their families a place to learn about brain metastases from a patient perspective.”

The site is a source for the latest information about this form of the disease, as well as for personal stories from women who’ve been there about what it’s like to be diagnosed and treated for “brain mets.” The site is written and maintained by patient advocates who work with scientists and physicians in a research Center of Excellence that focuses exclusively on understanding and treating breast cancer brain metastases.

Check it out, and let the sponsors know what you think.

Of milk and of aromastase inhibitors—Posters 2028 and 2080

I looked at two posters this morning that were relevant to work that BCA has been doing. Both, as it turns out, were prepared by members of BCA’s Scientific Advisory Board.

Dr. William Goodson presented a poster (2028) showing that milk products are a source of dietary progesterone. The conclusion of his study states:

Early breeding of dairy cows was instituted in the mid 20th Century to increase production. We demonstrate that the resulting progesterone in high-fat dairy products is rapidly absorbed leading to a detectable increase in bio-available progesterone in individuals consuming such products. Given the magnitude of milk use, we must consider the possibility that a single change in food production technology might have a major influence on the health of young persons who, with the best of intentions, are encouraged to drink milk.

 

Dr. Al Eisner’s poster (2080) focused on the increased prevalence of retinal hemorrhages among anastrozole users. The study is preliminary, but suggests that it is important to look for potential adverse impacts on vision from the use of AI’s.

Insulin and breast cancer—a plenary overview (Abstract P-3)

Michael Pollak from McGill University led the breast cancer folks here into the world of insulin, examining the rationale for suspecting an insulin connection to the disease both in terms of risk of incidence and prognosis, the evidence that insulin and IGF-1 signaling are relevant in breast cancer, and the clinical implications of information on insulin and IGF-1, including consideration of drug development possibilities. He reported that more than $1 billion is currently invested by drug companies that are developing products focused on the role of insulin in breast cancer.

Pollak closed by looking at metformin, a commonly used diabetes drug that lowers hyperinsulinism, wondering aloud whether breast cancer patients who express high levels of insulin might see benefit from the drug. As he noted, this would be a matter of choosing treatment not based on the disease characteristics, but on the characteristics of the woman, or host organism.

His slide presentation is worth a look, and is on the SABCS website. Just click on “Daily Slide Reviewer” under “Enduring Materials” on the home page, and then look at Presentations Day 2, Plenary 2.

The “omics” presentations

This session, which is the last scientific one I attended today, was introduced by the chair as representing the exciting place where basic science is being translated into clinical practice. And while that may be where the genomic revolution is going, we’re certainly not there yet.

The presentations made in this setting were from researchers looking at gene signatures of tumors or aspects of tumor biology that might indicate important information about prognosis, or, less frequently, treatment.

The most interesting presentation was from Joe Gray of the University of California at San Francisco on Genomic approaches to breast cancer subset identification and treatment (Abstract 31). Gray and colleagues are developing genetic assays to predict responses to specific breast cancer drugs. When this technology is ready it should be able to tell patients which treatments will help them (and which won’t). And it will be cheap.

Let’s hope it happens soon.

There were other presentations on gene arrays, some using SNPs. (Abstract 32.) As described by Wikepedia, a single nucleotide polymorphisms—pronounced snip—is a DNA sequence variation occurring when a single nucleotide—A, T, C, or G—in the genome (or other shared sequence) differs between members of a species, or between paired chromosomes in an individual.

All of these types of presentations (see Abstracts 33, 34 and 35) looked at gene profiles that predict for worse outcomes in breast cancer, rather than how to derive treatments to improve those outcomes. So they were more interesting to scientists than to patients.

Into the Lion’s Den—the Genentech Advocacy Luncheon

BCA recently had succeeded in persuading a Food and Drug Administration (FDA) advisory committee to recommend rejection of Genentech’s application for marketing approval of its Avastin drug for metastatic breast cancer. The company is very unhappy with this result, so it was with great interest that I approached this by-invitation lunch meeting.

When I arrived, there were some very nice women waiting to check people in and hand them name tags. I was already wearing a name tag provided by SABCS, and said I wasn’t inclined to put on a second one, but was told that I wouldn’t be let into the room without the Genentech provided name tag. I knew this was serious when I noticed the armed guard at the door to the room. What is Genentech afraid of?

Equally unappealing to me was the fact that Genentech had decided that the way to run this luncheon meeting was to assign people to work groups based on various topics. I would much prefer an open conversation between the advocacy community and company representatives.

A very nice lunch was served, and then Genentech reps began the meeting. They noted that the purpose of this meeting was to talk about data being presented at this conference, but acknowledged there would be questions about Avastin, so offered some information on this. As the presentation unfolded, the advocate seated next to me said she felt that she was part of a captive audience

Gwen Fyfe, Vice President for Clinical Hematology/Oncology at the company started off noting that the company believes in a very high bar for drug approval, and that doing these studies in the US, with the US patient population matters.

Next we heard a long presentation from Chris Bowden, who runs the Avastin group at Genentech. Chris presented some of the slides that the company presented to the FDA in support of their application for approval. He also made several points that explain why overall survival is not the primary endpoint that Genentech is focusing on for approval of Avastin:

  • Progression Free Survival (PFS) in the metastatic setting is not confounded by other treatments
  • The survival curve stayed separated until 30 months out, and overall survival was statistically significant at 1 year, though not at 2 years following beginning of treatment
  • While 6 people died from treatment on the Avastin arm, the number of deaths on the taxol arm is unknown due to how ECOG, which ran this trial, collects data

In response to questions posed by advocates, Bowden explained that there was clearly disagreement on the ODAC about approving a drug based on PFS, and noted that the first vote of the committee indicated that PFS is an important endpoint in the metastatic setting.

Gwen Fyfe ended the open discussion of Avastin, saying that the FDA needs to be skeptical, given its mission.

At this point, a Genentech representative made a presentation on the companies approach to breast cancer drugs, and the drugs they have in trial.

Noting that Herceptin is about to celebrate 10 years since its approval, the company has prepared a time line of significant events in this period that conveniently ignores the struggle for compassionate access to the drug.

We learned that in cases where Herceptin doesn’t work for Her2 positive patients, Genentech refers to Herceptin “escapes,” rather than treatment failures. One of the activists mentioned to me that she had noticed for the first time today that the definition of what cardiotoxicity is from Herceptin differs across the various trials of the drug in the adjuvant setting.

And we learned that the company is testing a new drug that targets a different part of the Her2 pathway, called pertuzumab or 2C4. The company is testing this drug in a double blind trial called Cleopatra that compares Herceptin alone to Herceptin plus pertuzumab. I cold only wonder how much pertuzumab will cost, if it gets FDA approval. After all, Herceptin alone already costs $50,000 a year.

Once these presentations were over, it was time for the pre-determined workgroups, but the folks concerned about Avastin broke out of their assigned groups to talk with Gwen Fyfe and Pam Klein. Klein, until yesterday was the Genentech Vice President, Clinical Oncology, Hematology and HER Family. (She’s resigned to take a new path.) In this discussion, we heard a number of additional things about the company’s reaction to the Avastin recommendation, and their attitude toward PFS and overall survival (OS) in drug trials in the metastatic setting.

  • Genentech decided not to do a registration trial (for FDA approval) after it’s first trial of Avastin in breast cancer failed
  • They would need to have 2000 people in a trial to be able to measure 3 months of overall survival, meaning that survival is not a viable end point, given the standard of care in the United States where people get lots of different treatments, making it hard to determine which drug is responsible for “survival.”
  • The Avastin trial was not powered to show survival, but trend for survival was still seen.
  • The company believes that Avastin has been held to a higher standard than Tykerb (lapatinib) by the FDA.

The Avastin discussion ended with a hope expressed by the advocates that there would be more conversations with the company about concerns related the standards for approval of their drugs in general, and Avastin in particular.