TDM-1 for treatment of breast cancer

About a decade ago, a patient diagnosed with cancer, had a few options. If the disease was localized, (at one spot only), and could be surgically removed, it was resected. If surgery was not an option the patients were either given localized radiation therapy or their bodies were flushed with chemotherapy drugs that indiscriminately attacked more or less all cells in the body. If the cancer was metastatic, i.e. spread across multiple sites, chemotherapy was the preferred course of action. But the unwanton targeting of all cells in the body led to extreme side effects including hair loss, extreme fatigue and fertility issues resulting in overall reduction of the quality of life of patients.

But in the past decade and a half, the pharmaceutical companies have veered away from one shoe fits all strategy by developing treatment options tailored to the patient’s disease. These therapies take in account the genetic component of the disease (genes being shut down, proteins being over-produced etc.) and specifically target those cells. The EMILIA study published in the New England Journal of Medicine in October 2012 studies the safety of one such therapy[1].

In about 20% of the breast cancer cases, a protein called human epidermal growth factor receptor 2 (HER2) is over-produced and present on the cancer cell surface[1]. Currently, these patients are treated with a combination of trastuzumab and taxane. While trastuzumab is an antibody (a protein that mimics the body’s immune system) and targets the cells that express HER2, taxane destroys microtubules, the cell machinery needed for dividing cells[2].

For patients whose disease is advanced and spread to multiple sites and couldn’t be contained by conventional treatments, a combination of capecitabine (a DNA blocker) and lapatinib (an inhibitor of the HER2 pathways) is used. Scientists at Genentech developed an alternative therapy called trastuzumab emantisine (TDM-1) which links the HER2 antibody trastuzumab with the microtubule destroying derivative drug of maytansine (DM-1) that is toxic to cells[1]. The EMILIA study compares these two therapies for patients whose disease has progressed on trastuzumab and taxane.

Scientists found that for patients receiving TDM-1, the cancer did not grow for an average of 9.6 months versus 6.4 months on capecitabine and lapatanib. Also, fewer patients (40.8%) reported serious side effects than those on capecitabine and lapatinib (57%). The most common side effects for patients getting capecitabine and lapatinib, were sever diarrhea (20.7%) and hand-foot syndrome(16.4%), i.e. the swelling, redness and tenderness of palms of hand and feet. In contrast, the side effects of TDM-1 patients were decreased platelet count(12.9) and increased liver function(4.3%), both controlled by modification of drug regimen.

TDM-1 therapy thus provides patients with an alternative option.

References:
1. Verma et. al. Trastuzumab Emtansine for HER2-Positive Advanced Breast Cancer. The New England Journal of Medicine. October 1, 2012 DOI: 10.1056/NEJMoa1209124
2. Bullock et. al. Clinical Efficacy of Taxane–Trastuzumab Combination Regimens for HER-2–Positive Metastatic Breast Cancer. The Oncologist May 2008 vol. 13 no. 5 515-525.

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2 Responses to TDM-1 for treatment of breast cancer

  1. Gabor Nemeth says:

    Dear Vilay Khandelwal,

    My sister in law has this metastatic HER2 type cancer. She’s going to get chemotherapy combined with Herzeptin (produced by Roche) as a biological therapy. A professional friend of mine advised to look forward clinical studies where this new TDM-1 is being tested. Could you please suggest where shall we look for these studies?
    She lives in Munich, Germany.

    Any answer would be highly appreciated! Thank you in advance!

    Cordially,
    Gabor Nemeth

    • Vilay Khandelwal says:

      Hi Gabor,

      I am not a medical professional and cannot guide you in terms of the specifics. I would recommend checking out local listings of the drugs. In the US, FDA makes it essential for all clinical trials to be listed on ClinicalTrials.gov. Germany might also have such a site. If not, I would recommend contacting Roche Germany and asking them for their trials that are open. These companies are always looking for more patients to be enrolled onto their studies and am sure would welcome an inquiry form you.

      Hope this was helpful.
      Vilay

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