PracticeUpdate Oncology Best of 2018

EXPERT OPINION 22

Dr. Sara Hurvitz on Management of HER2- Positive Metastatic Breast Cancer Interview with Sara A. Hurvitz MD by Ana C. Sandoval Leon MD PracticeUpdate caught up with Dr. Sara Hurvitz, Director of the Breast Oncology Program at the UCLA Jonsson Comprehensive Cancer Center in Los Angeles, California, at the Miami Breast Cancer Conference. Dr. Sandoval Leon: Let’s talk a little more just in general about HER2- positive metastatic breast cancer. What is your current approach to manage these patients? Dr. Hurvitz: For the patient with HER2-positive metastatic disease, we’re pretty good at defining what our first-line and second-line therapy should be. First-line therapy should be taxane with tras- tuzumab and pertuzumab based on the CLEOPATRA study. The chemo should be given for four to six cycles until a good response is achieved, and then the chemo can be dropped. Personally, I " There are a number of different chemotherapies that have been evaluated that are HER2-targeted. We can use trastuzumab, we can use lapatinib; however, the mantra is to always keep the foot on the brakes of HER2 in HER2-positive disease. " Dr. Hurvitz: The most exciting ADC for HER2-positive breast cancer in my opinion is DS-8201. This is an ADC in which the cytotoxic payload is a topo [topoisomerase] I inhibitor. It is a unique mole- cule because the payload-to-antibody ratio is quite high; so, a lot of drug is getting in. Phase I data are from a pretty large cohort: one cohort has HER2-positive disease and the other has HER2 low-expressing disease. In 1+ or 2+ disease, we’re seeing objec- tive response rates on the order of 60% in HER2-positive and over 30% in HER2 low-expressing. The safety profile looks exciting. The median progression-free survival is greater than 10 months, and An Overview of Chemotherapy-Induced Heart Failure Interview with Joerg Herrmann MD by Jennifer N. Caudle DO will then add in endocrine therapy if the tumor co-expresses the hormone receptors, but that wasn’t the way CLEOPATRA was designed. In the second-line setting after a patient has progressed on trastuzumab, the standard of care is T-DM1, and then after that it’s anyone’s choice. There are a number of different chemother- apies that have been evaluated that are HER2-targeted. We can use trastuzumab, we can use lapatinib; however, the mantra is to always keep the foot on the brakes of HER2 in HER2-positive dis- ease. So, a patient should always be receiving an HER2 inhibitor in addition to chemotherapy or endocrine therapy. Dr. Sandoval Leon: You talk a lot about the ADCs [antibody–drug conjugates], and there are several in the pipeline. Which one do you see as the most promising currently?

Dr. Caudle: Could you briefly summarize the current importance in recognition of chemotherapy-induced cardiotoxicity and heart failure? Dr. Herrmann: It has, for a long time, not really made the press. I mean the anthracyclines,

cardio-oncologist it’s not really much of an impact for the therapy. But trastuzumab and then all these newer agents, collectively called targeted therapies, that became an issue. I mean if you have cardiotoxicity, drop in the ejection fraction, which is more common, or clinical heart failure – less common – and you can- not proceed with what you feel is the best therapy for the cancer patient, that is an issue. So that, I think, is really the relevance that we’ve recognized now for over a decade. Dr. Caudle: Two trials were presented regarding using heart failure treatment medications to prevent chemotherapy-induced cardiotoxicity. Can you explain why this data is so important? Dr. Herrmann: Yeah. It comes with a first question, I mean, the dark implication is well if it’s impairing delivery of best cancer care and cure rates, and then possibly survival, that is an issue. And trastu- zumab has been shown, I mean those patients who do develop cardiotoxicity or have interruption of therapy, they don’t do as well as those who can just go on with their 1 year of adjuvant therapy for instance. So looking for ways to prevent them to have a drop in the actual infection is really critical. As far as cardiology we would say, “It’s a no-brainer”; you’ve got to protect the heart. But for the oncologists it’s really also this aspect, “Can we then continue with the therapy as much as we want to?” So I think that’s why these trials are important and why I’m sure we’re going to see more and more of these in the years to come. There have already been a number done. I have to mention these two mainly related

they’ve been around since the 1960s…they were discovered in the 1970s, but we all know anthracycline-induced cardiotoxicity based on our education. But what really changed was in 2001 when the results of the pivotal trastuzumab trial were published. And then, for the first time, there was an incidence of almost 30% of heart failure, at times life-threatening, which became the major game-changer. And one unique difference from all that we had before is that it actually affected the delivery of the chemotherapy. And so, it got really close to home for the oncologists. Anthracycline cardiotoxicity is often late, it can be decades later, when they’re all cured and often forgotten. So for the " If it doesn’t allow the oncologist to complete chemotherapy, that’s really an issue. And so, we will see more formulated and, hopefully with the trials being presented, more and more guideline type style of recommendations. "

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