Barbara Brenner, Former Executive Director

Things are starting to slow down here. People are heading home. The exhibit hall is almost empty of folks checking out the booths. And, despite what you read in the newspaper, the emerging consensus among the people I know here is that there is really nothing groundbreaking that’s coming out of the meeting in any way that might be meaningful now to patients.

Breast Cancer Language: When Will We Learn?

I skipped this morning’s plenary session, since it was one of those pathway talks. But I entered the general session room as the presenter was finishing. I heard him say two things that made my blood crawl. The first was something about “resalvaging” a patient. I took this to mean that a patient for whom amore than one previous treatment had failed, benefited from something given later. I’ve always wondered about the word “salvage” used in breast cancer. It’s most commonly used in reference to a mastectomy that occurs after a local recurrence in a women whose initial surgery was lumpectomy. It’s called a “salvage” mastectomy. I’ve always wondered whether what was being salvaged in this instance was the surgeon’s reputation. But “resalvaging”? Puhleeese!

The same presenter –keep in mind this is the end of 2009 — referred to what you do when a “patient fails” treatment. But patients don’t fail treatments; treatments fail patients. I’ve been the rounds on this topic at SABCA before. It seems that constant vigilance is required to make sure that everyone involved in breast cancer understands that words really do matter.

Unfortunately, that vigilance extends to advocates as well. At the Genentech advocate meeting this evening, more than one patient advocate referred to herself as failing treatment. Sigh.

Herceptin+Tykerb for metastatic patients – don’t believe the news reports

At about 10 p.m. on Friday (last night), Jane Zones sent me an e-mail containing the already published AP report on Abstract 61, which was presented this morning at this meeting. Reading the press report made me think that we would be getting an exciting report about a breakthrough for women with Her2 positive metastatic disease whose breast cancer had progressed while on Herceptin treatment. Boy, was I surprised.

Kim Blackwell, whose financial disclosure page was quite long, presented the updated survival data for a randomized study of Tykerb (lapatinib) or in combination with Herceptin in heavily pretreated women. This trial (EGF 104900) allowed women in the lapatinib arm whose disease progressed during the trial to cross over to the combined treatment arm, and 52% of them did.

OS seen at this time in this trial shows a statistically significant benefit of the combined therapy of 4.5 months (26%). The factors that influenced the survival difference were:: treatment assignment, ECOG performance status (a measure of the patient’s ability to function normally), site of disease, metastatic sites, and time from initial diagnosis until randomization. According to Blackwell, adjusting for these factors resulted in a still statistically significant, but smaller benefit.

Safety signals were worse in the combined treatment harm but there was no increased in cardiac problems by adding Tykerb to treatment.

Blackwell closed her presentation by noting that there is an ongoing trial of 8000 women, called ALTTO, evaluating combined Tykerb and Herceptin at an earlier stage of disease.

In making her presentation, Blackwell referred to a new measure of effectiveness — “clinical benefit rate” – which she described as a combination of complete response, partial response and stable disease. It’s clear to me that the introduction of this new “measure” is addressed to the emerging practice at the FDA’s drug evaluation branch to look at whether surrogate markers for benefit, like PFS, provide “clinical benefit.” In light of the statement made in yesterday’s session that “clinical benefit” is somewhat subjective, the attempt to give it the cloak of objectivity is quite troubling.

Equally disturbing is the response that Blackwell gave to a statement made after her presentation by Kathleen Pritchard from Canada. The statement was that the data don’t show that adding Tykerb does anything for patients, but rather show that continuing tamoxifen is useful. Blackwell responded that this is an accurate statement.

So, what’s been reported in the press as an exciting breakthrough is anything but. And the cost of adding a treatment – Tykerb — that has not been shown to improve outcomes in these kinds of patients is huge – over $40,000 a year.

Genentech Advocacy Briefing – an ongoing dialogue

Every year the drug and biotech companies wine and dine the advocates at this meeting, trying to engage them in interest in the companies’ work. Genentech has always done a good job with this, and this year was no exception. This year the event was not as well attended as it sometimes is (it’s invitation only, but I don’t imagine they issued fewer invitations than in the past). That may have to do with competing events or the fact that the gathering was held at 8 p.m. on the last night of along conference.

We heard from Sandra Horning, the newly appointed global head of clinical development hematology/oncology for the company. She mostly wanted to introduce herself and tell us about her commitment to Genentech’s mission. She also got her cancer cred: she told us she’s a breast cancer survivor. We didn’t hear much of substance from Sandra, but she says she’s a good listener and wants to hear from people.

Robert Schueren, senior director of the diagnostics group, talked about the search for biomarkers that don’t leave behind someone who might benefit. He didn’t make a breast cancer connection.

Julie Hambleton, who is very involved with the companies work on Avastin, talked about the ongoing research involving Avastin and breast cancer, and mentioned that Genentech has submitted additional information to the FDA in support of extended the Avastin drug label in the breast cancer field. She noted – as everyone in the room knew – that there are no trials showing that Avastin increases overall survival for metastatic breast cancer patients. She pointed to the progression free survival advantage of the drug, and noted that there is “no detriment to survival.”

Hambleton also noted that the more rigorous trials of the drug in metastatic disease showed less PFS advantage than the trial (E2100) that led to fast-track approval by the FDA.

While Hambleton insisted that everyone at Genentech wants drugs that improve overall survival and improve quality of life, the company will continue to push for approval of its therapies based on PFS, believing that patients should have this choice.

The company is preparing to ask the FDA for fast-track approval of TDM1 in metastatic patients for whom Herceptin has stopped working. TDM1 is an “armed” formulation of Herceptin (Trastuzumab is the “T” in TDM1) to deliver both Herceptin and a cytotoxic therapy to the tumor. A poster – number 710 — was presented on the phase II trial of this drug, but I just spent a half hour searching for it on the SABCS site and could not find it. Genentech has issued a press release.

Because there is so much excitement about TDM1 and the shrinkage of tumors in 33% of the 110 women in the trial, questions were raised about whether the company would offer expanded access to the drug for those not eligible for trials of TDM1. The response was that the company will look at expanded access if further trials are called for by the FDA. Note that there has been no completed Phase III (efficacy) trial of TDM1.

Since a year ago Genentech staff at this same briefing said the company would never again offer expanded access, I was encouraged to hear that there is some openness to revisiting this issue.

Heard In the Halls

As I was leaving the presentation hall, I heard the next presenter, Dennis Slamon, say that reading the financial disclosure list for the researchers on the study he was about to present would take up all his time. What he did not go on to say is that it’s almost impossible to find doctors and researchers who don’t have financial conflicts. An outstanding exception is Stefanie Jeffrey, surgeon and researcher at Stanford, who as a matter of policy does not accept funding from businesses with which she works.

The mammography discussion is on going here. One tidbit I picked up for other activists who are here is that we should change some of our own language. Currently, we tend to refer to an individual’s experience with screening as an anecdote. To improve our ability to have a useful conversation about screening and its benefits and limitations, It would be better to refer to these experiences as personal stories.

And Komen is dipping its toe into the issue of environmental causes of breast cancer again. I hear that the Foundation has given at grant to the Institute of Medicine to do a critical review of the evidence of environmental links to breast cancer, and to prioritize areas of further research. Komen previously funded work from the Silent Spring Institute to investigate the available published evidence on the links between environmental contaminants and breast cancer. The results of that research were published in the journal Cancer.