“Miracle…breakthrough…magic bullet” news flooding from ASCO meeting

Greg Pawelski

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?

Elaine Schattner

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.