Health News Review

This is a familiar story now being re-told.  Excitement over an experimental drug is conveyed with unnecessarily sensational language that doesn’t help anyone. That’s what happened in recent days with some – not all – news about the experimental drug T-DM1 coming out of the American Society of Clinical Oncology meeting in Chicago. It would be better if journalists stuck to the evidence, explained what “progression-free survival” means, and helped readers hone their critical thinking.

Another old pattern revisited:  When the New York Times reports something, the TV networks are soon to follow.
So when the Times reported, “A new class of cancer drugs may be loss toxic,” featuring a single patient’s experience with T-DM1 – NBC followed closely and quite similarly – featuring the exact same patient in the exact same setting. One woman out of 1,000 in the trial.  Who chose her?  The drug company PR people?

NYT TDM-1 story
New York Times T-DM1 story
NBC TDM-1 story
NBC T-DM1 story

It was refreshing to see Liz Szabo’s USA Today piece on the same drug.  Excerpts:

  • 2nd sentence: “The experimental drug, T-DM1, doesn’t cure anyone.”
  • Later: “People should be cautious about overestimating T-DM1′s survival advantage, because, statistically, it’s possible that those findings could be due to chance, Horning says. As researchers continue to monitor the women’s progress, doctors will get a better sense if T-DM1 really improves survival.”

Stay tuned.  The ASCO conference continues this week.

 

Addendum later on June 4:

The Retraction Watch blog notes that the lead author of the T-DM1 study announced at ASCO co-authored two corrected papers with Anil Potti, the “now-former Duke oncologist who has retracted or corrected 17 papers after resigning in the midst of an investigation into his work.”

Addendum on June 6:

See “T-DM1: ASCO Showcases a Victory for Science, But Is It a Victory for Women?” by Laura Nikolaides, director of research and quality care programs for the National Breast Cancer Coalition.

 

 

Comments

Jody Schoger posted on June 4, 2012 at 10:52 am

The model “pharma” patient is always white, suburban, with lovely artwork, color coordinated roses and a calm, meditative stance.

Ah. Cancer should look so good.

Thanks again
Jody

    kgapo posted on June 4, 2012 at 4:30 pm

    When I saw the picture on this article I was wondering whether it pertained to it. Too beautiful ….Jody rightly notes this cannot be the kind of cancer patient we know… for many reasons…

AnneMarie posted on June 4, 2012 at 11:31 am

Headlines and soundbite are SO damaging and too many do not look beyond just those headlines and soundbites. Kudos to “our” journalist advocate, Liz Szabo for always telling it like it is….

Greg Pawelski posted on June 4, 2012 at 2:05 pm

A comment on one of the cancer boards, by the headliner in the above article (Fern), stated that a lady who was doing well on the T-DM1 trial, discovered she had 15 brain tumor mets. T-DM1 is a “large molecule” and does not cross the blood-brain barrier (BBB). She thinks on the T-DM1, they should also give the ladies some straight Herceptin, which she thinks will cross the BBB and give a certain amount of protection. The only way for that to happen is a patient may also have to be subjected to an “intrathecal” injection of T-DM1. Herceptin does not cross the BBB because it is a “large molecule” drug. Fern also had a small metastasis to the brain. She stated that she’ll be on T-DM1 “indefinitely” or until progression.

There were a number of caveats about Herceptin. Aside from the issue of congestive heart failure, past studies have suggested a potentially very serious weakness in the drug, the problem with central nervous system (CNS) metastasis. A study from the Dana Farber Cancer Institute identified CNS metastases in women who received trastuzumab-based (Herceptin) therapy for metastatic breast carcinoma. CNS metastases were identified in 34% of patients at a median of 16 months after diagnosis of metastatic breast cancer and 6 months from the beginning of Herceptin treatment. Patients receiving Herceptin as first-line therapy for metastatic disease frequently develop brain metastases while responding to or stable on Herceptin.

The trial found that trastuzumab emtansine (T-DM1) can improve progression-free survival in “some” women with metastatic breast cancer. The final arbiter of clinical approval is overall survival. Median overall survival for patients treated with T-DM1 was not reached. Drug response is not a reliable predictor of overall survival. Median progression-free survival was longer in patients treated with T-DM1 than in those treated with the standard therapy (9.6 vs 6.4 months). The difference reached is statistically significant?

The so-called immunoconjugates or antibody-drug conjugates (ADCs) are unique therapeutics that have become the focus of a plethora of recent and ongoing clinical trials, and for the first time since 2000 when Mylotarg (gemtuzumab ozogamicin) was approved in AML, the FDA gave the green light for another ADC, namely Adcetris (brentuximab vedotin) for the management of Hodgkins Lymphoma (HL) and systemic anaplastic large cell lymphoma (sALCL), like its sister agent in HER2-positive breast cancer, T-DM1, and other ADCs.

The ADCs do not work for all patients, T-DM1 is meant to treat only roughly 20 percent of breast cancer cases characterized by an abundance of that protein, and they are not totally free of side effects. And of course, T-DM1 is also likely to be very expensive, costing more than $100,000 for a typical course of treatment. One note: Mylotarg was removed from the market in 2010 after newer studies showed it did not prolong lives and had safety problems. At initial approval, Mylotarg was associated with a serious liver condition called veno-occlusive disease, which can be fatal.

One thing you can definitely say is that T-DM1 is an investigational agent, or just plain experimental. And the “crowd” wants the FDA approval ASAP?

Holly Anderson posted on June 4, 2012 at 2:47 pm

It is really aggravating to see how many news sources hyped this one up. Here was my Facebook posting yesterday morning when I read about the new “wonder drug” as one story hyped:
“Really? REALLY? A gain of three months before ‘progression of disease’ is a WONDER DRUG? Pardon my cynicism about T-DM1 but another “wonder drug” that offers no cure, and will undoubtedly be priced off the charts, and is hitting the media today like it’s the holy grail, is NOT progress, people, if it only buys 3 months of PFS and may not impact the endpoint. What are we seeing today? Essentially a lot of hype and some free marketing for Genentech and ImmunoGen- makers of the “wonder drug” combo. Her-2/Neu positive folks need a cure, not a 3-month reprieve.
(I learned to question what I read from some of the best, including Health News Review.)

Elaine Schattner posted on June 5, 2012 at 7:10 am

Gary, I think you’re too quick to dismiss progress. Forget the quotes and anecdotes, the data (though not good enough) are seriously encouraging. “Cure” is not the only goal of cancer therapy. And 3 months was the difference between the 2 drugs, not the absolute duration of disease control. The single, less toxic drug’s effect lasted a median of over 9 months.

    Gary Schwitzer posted on June 5, 2012 at 7:41 am

    Elaine,

    You know the purpose of our project well enough to know that we focus on journalism.

    There isn’t one thing in what I wrote nor in what I intended to convey that “dismisses progress.” I wrote about the journalism. You’re writing about the science. The quotes and the anecdotes that you say I should forget are at the very heart of any critique of the journalism.

Musa Mayer posted on June 5, 2012 at 6:21 pm

Gary, I think one problem that plagues reporting on cancer drug development trials is the misreading or misunderstanding some writers (not science writers, hopefully) have with the endpoint of PFS, or progression-free survival. Clearly, several articles, mostly in the popular press, thought that this meant that patients lived longer, while others thought that PFS meant patients were disease-free during that additional 3.2 months. It’s really too bad that TTP, or time to progression, wasn’t retained as the term used to represent the time until the disease progresses by FDA. Perhaps then patients and media folks wouldn’t get this wrong so often.

To Greg Pawlewski, there is no indication that Herceptin actually causes brain and other CNS metastases in HER2+ metastatic breast cancer. The Center of Excellence of scientists and physicians I work with on this subject (see http://www.BrainMetsBC.org ) feel that the relationship is one where the brain becomes a “sanctuary” site where HER2+ disease that is well-controlled outside the brain by Herceptin grows because these patients are living long enough to get this form of metastasis, which happens in at least a third of metastatic patients. Herceptin is too large a molecule to get through an intact blood-brain barrier, but interestingly, multiple studies suggest that women who continue to receive Herceptin after being diagnosed with brain mets, live twice as long as those who do not receive Herceptin. One reason why might be that Herceptin suppresses extra-cranial metastases seeding new brain mets. Brain metastases are even more common in triple-negative breast cancers.

    Greg Pawelski posted on June 5, 2012 at 9:04 pm

    To Musa Mayer. Aside from the issue of semantics (no indication that Herceptin actually causes brain and other CNS metastases), Dana Farber Cancer Institute identified central nervous system (CNS) metastases in women who receive trastuzumab-based (Herceptin) therapy for metastatic breast carcinoma (Cancer 2003 Jun 15;97(12):2972-7). Central nervous system disease is defined as one or more brain metastases or leptomeningeal carcinomatosis (carcinomatous meningitis). CNS metastases was identified in 34% of patients at a median of sixteen months after diagnosis of metastatic breast cancer and six months from the beginning of Herceptin treatment. Monoclonal antibodies like Herceptin are very large molecules which do not have a convenient way of getting access to the large majority of cells. Plus, there is multicellular resistance, the drugs affecting only the cells on the outside may not kill these cells if they are in contact with cells on the inside, which are protected from the drug. The cell may pass small molecules back and forth.