You Will Remember This Day

Kathy D. Miller, MD


February 21, 2013

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Hi, everyone. It's Kathy Miller from Indiana University with another quick Medscape Oncology blog. I've been thinking about momentous days in history, days that we will always remember for good or bad, when the world stopped and you remember where you were when you heard the news.

We have had some of those moments lately in oncology. Think of that day at the American Society of Clinical Oncology meeting in 2005 when the first adjuvant trastuzumab results were reported.[1] The world stopped, and it was the first and probably only time in my professional career that there was a standing ovation at a scientific meeting.

We are about to have another one of those days in the HER2 world. On or about February 26, 2013, we will hear whether there is US Food and Drug Administration (FDA) approval of T-DM1(trastuzumab emtansine). This novel agent takes trastuzumab to the next level, linking it with chemotherapy in a way that allows the chemotherapy to be delivered almost exclusively to the tumor cells, sparing the patient and the rest of her healthy body the toxicities of the therapy.

We have talked about T-DM1 before, but let me just remind you of the strength of the results of the EMILIA trial.[2] EMILIA randomly assigned patients who had had previous trastuzumab and chemotherapy in the metastatic setting to an FDA standard, capecitabine plus lapatinib, or T-DM1 monotherapy. This is the classic light-beer scenario: It's less filling and tastes great. T-DM1 was more effective by every measure: improvement in overall response rate, disease-free survival, progression-free survival, overall survival, and less toxicity. It was a clear winner if ever there was one.

Think about what this means for our patients. Our HER2-positive patients with metastatic disease have another very powerful therapy that offers a real hope for prolonged disease control with less toxicity. We are still learning how to properly use this agent and the setting in which it might best be used. We have seen tantalizing results of randomized phase 2 studies comparing this agent as monotherapy with chemotherapy and trastuzumab in the first-line setting. The large MARIANNE trial[3] has still to give us results, and they are very much awaited.

I expect that we will soon see adjuvant trials looking at our lower-risk patients. Might we do away with systemic chemotherapy at all? Might we rely solely on this agent? Might we replace a component of the chemotherapy for our higher-risk patients with this agent? This is really what we have all been waiting for -- taking the molecular biology, understanding a patient's tumor and that driving factor, neatly defining a therapy that would interrupt that factor, and then taking it a step further. It brings bright days to our patients and gives great hope for things to come. I would love to hear your thoughts and your experiences with this agent.