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  • ASCO Update: 2012

    For breast cancer clinicians and clinical researchers, the two major meetings each year are the American Society of Clinical Oncology (ASCO) and the San Antonio Breast Cancer Symposium (SABCS).  ASCO takes place in Chicago, generally in early June.  As you might imagine, SABCS is always in San Antonio, and is typically in early to mid December.  In recent years, there have been a number of advances that have been presented at these meetings, and we have come to expect at least one or two major findings at each. 

    Progress for HER2+ breast cancers 

    Without question, the biggest news from ASCO this year was related to T-DM1, the newest of the drugs for HER2+ breast cancer.  T-DM1 is big news because it is a very effective new agent, and because it represents a promising new class of drugs called antibody drug conjugates.  T-DM1 is essentially two drugs in one.  Trastuzumab (Herceptin, an antibody that targets HER2+ cancer cells) is attached to DM1, a very potent chemotherapy.  When given alone, DM1 has severe side effects.  However, when DM1 is combined with trastuzumab, the trastuzumab delivers the chemotherapy directly to the HER2+ cancer cells.  Trastuzumab does double duty.  It plays the same role it always plays when given with chemotherapy (adding to the chemotherapy’s ability to kill cancer cells).  At the same time, it allows the DM1 chemotherapy to target only the HER2+ cancer cells. This spares the normal cells.  As a result, T-DM1 is not only highly effective, but is also associated with few side effects. 

    In the EMILIA study, T-DM1 was compared to capecitabine and lapatinib in persons with HER2+ metastatic breast cancer whose cancers progressed (worsened) on a trastuzumab-containing regimen.  T-DM1 increased the time to progression (until the cancer worsened) compared to capecitabine and lapatinib.  And, early findings suggest it may also improve survival.   Perhaps what is most impressive is that T-DM1 is so well tolerated.  There is no hair loss, no nausea, no diarrhea and no risk of infection.  There can be a brief fall in the platelet count with T-DM1, but this is almost always asymptomatic (without symptoms).  Other side effects are rare. 

    Based on the EMILIA results, it is likely T-DM1 will be approved by the FDA in the months ahead, and most of us expect it will be commercially available in early 2013.  At first, it will be used in patients who have previously received trastuzumab. More studies are underway however, and it may have a role in persons with newly diagnosed HER2+ breast cancer.  In the meantime, discussions and plans are underway to study T-DM1 in the adjuvant and preoperative settings.  I believe T-DM1 may truly change the way we care for many patients with HER2+ breast cancer, and that ultimately it will be used quite broadly.  The hope, of course, is that T-DM1 will give rise to many new drug antibody conjugates.  Whether they are as effective as T-DM1 remains to be seen, but there is great interest in this novel approach to cancer therapy.  

    Advances in chemotherapy for HER2- breast cancer 

    The other two studies from ASCO focused on chemotherapy approaches for women with HER2- breast cancer.  The first trial, NSABP B-38, compared the ability of three different chemotherapy regimens to prevent a recurrence of breast cancer.  The study found two common chemotherapy regimens, TAC (docetaxel, Adriamycin, and cyclophosphamide) and dose dense AC-T (Adriamycin, cyclophosphamide followed by paclitaxel) were equally effective in preventing recurrence.  Moreover, the NSABP found that adding the drug gemcitabine to the combination added toxicity, but did not reduce recurrence rates.  Based on this trial, we can conclude that either AC-T given in a dose dense (every two weeks) manner or TAC can be used interchangeably in clinical practice.  Decisions about which regimen to use should be based on side effects and the oncologist’s comfort and experience with a particular regimen. 

    The second trial was CALGB 40503, a clinical study that compared paclitaxel to either nab-paclitaxel or ixabepilone in the treatment of women with metastatic breast cancer who had not received prior chemotherapy for their metastatic disease.  All of the treatments were given with bevacizumab (Avastin).  The study showed nab-paclitaxel was no better than paclitaxel, and ixabepilone was inferior to paclitaxel.  In both cases, the therapy under study was more toxic than the standard treatment (paclitaxel).  While the CALGB researchers and their colleagues had hoped that one of the new treatment regimens would be better than paclitaxel, the study nevertheless provides important information.  It clearly shows a commonly-used drug (paclitaxel) is less toxic (and far less expensive) than these newer drugs and should remain the standard.  The study was conducted through cooperative group research and funded by the National Cancer Institute.  It underscores the importance of cooperative group research in identifying standard clinical approaches.   

    Final thoughts 

    Of course, there were many other findings at ASCO, but I have tried to hit the highlights.  Progress has not been as rapid as we would like, but each year we are seeing significant advances.   To speed up progress, we need strong collaborations between researchers and clinicians, and we need to ensure there is adequate funding for clinical trials.  Collaborations have been blossoming in recent years and if we can solve our challenges related to funding, there is every reason to be hopeful as we move forward.


    Posted June 27, 2012