Kathy D. Miller, MD; Ian E. Krop, MD, PhD


December 24, 2013

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In This Article


Kathy D. Miller, MD: Hi. I'm Kathy Miller, Associate Professor of Medicine at Indiana University School of Medicine in Indianapolis. Welcome to this edition of Medscape Oncology Insights.

Today we will look at several key studies in HER2-positive breast cancer presented at the 2013 San Antonio Breast Cancer Symposium. To join me in that discussion is Dr. Ian Krop, Assistant Professor of Medicine at the Harvard Medical School and Director of Clinical Research for the Breast Cancer Program at the Dana-Farber Cancer Institute. Welcome, Ian.

Ian E. Krop, MD, PhD: Thanks for having me.

NeoALTTO: Long-term Data on Dual Blockade

Dr. Miller: Let's talk first about neoadjuvant therapy, an area in HER2-positive disease that got a lot of attention earlier this year with the approval of pertuzumab, the first agent with that new mechanism to have accelerated approval. We have seen the data for NeoALTTO (lapatinib, trastuzumab).[1] Is that type of dual inhibition also effective? Where does that stand?

Dr. Krop: The idea of the approval for pertuzumab was predicated on the concept that improvement in the neoadjuvant setting as measured by pathologic complete response (pCR) rates would translate into long-term outcomes. Obviously, that is the endpoint that we really care about. We had clear data from the NeoSphere study[2] for pertuzumab added to trastuzumab-based therapy, and that is what led to the accelerated approval of pertuzumab.

We have similar data from the NeoALTTO study looking at the combination of lapatinib with trastuzumab -- again showing that the addition of lapatinib to trastuzumab (the dual blockade that you mentioned) clearly improves pCR. Now we have the first inkling into what happens in terms of long-term outcomes from dual blockade, and that was presented today by Martine Piccart-Gebhart,[1] who has the long-term outcome data from the NeoALTTO study.

Although this study was not powered to look at long-term outcomes, they followed slightly more than 400 patients. The data were available, and so everybody was certainly interested in what they found.

The data showed that there was no clear benefit in the overall population, with the addition of lapatinib to trastuzumab compared with trastuzumab alone. The hazard ratio was 0.78, but that was not even close to statistically significant.

Of interest, they looked at the ER-negative subgroup. They divided the patients into ER-positive and ER-negative/HER2-positive patients. In the ER-negative subgroup, the hazard ratio was a little bit more dramatic (0.65) -- not statistically significant, but clearly suggesting that there might be a real difference in terms of long-term outcome.

It was particularly interesting that if you look back at the NeoALTTO data, the biggest difference in pCR when comparing trastuzumab chemotherapy with trastuzumab and lapatinib chemotherapy was in the ER-negative subgroup. This suggests that it is possible that improvement in pCR translates into long-term outcome, but it is not definitive. It was not statistically significant, and we will need to wait for an appropriately powered study. Fortunately, we have that in ALTTO, which rumor has it that it will be presented sometime in 2014.[3]


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