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ESMO Breast 2021 | Adjuvant treatment for stage I HER2+ breast cancer

For patients with stage I HER2+ breast cancer, the importance of appropriate de-escalation for those who may be at lower risk requires further examination. Sara Tolaney, MD, Dana Farber Cancer Institute, Boston, MA, evaluates data on adjuvant treatment for stage I HER2-positive breast cancer, who despite being early-stage, still represent a risk for disease recurrence. Dr Tolaney touches on the APT trial (NCT00542451) which evaluated an abbreviated chemotherapy regimen to patients with stage I disease. Also discussed is the findings of the ATEMPT trial (NCT01853748) investigating T-DM1 versus paclitaxel plus trastuzumab in stage I HER2+ breast cancer. This interview took place at the virtual European Society for Medical Oncology (ESMO) Breast Cancer Congress 2021.

Transcript (edited for clarity)

Stage I HER2-positive breast cancer is a group of breast cancer that was really excluded from a lot of the pivotal adjuvant trials. You know, we didn’t really know at the time when trastuzumab was being developed, what the risk of stage I HER2+ disease would be for patients. We do now, however, have a lot of data that has accumulated over the years from retrospective series of untreated patients that suggests that patients who have stage I HER2+ breast cancer are at more than just an insignificant risk of recurrence with really rates of recurrence ranging as high as 30% in some series...

Stage I HER2-positive breast cancer is a group of breast cancer that was really excluded from a lot of the pivotal adjuvant trials. You know, we didn’t really know at the time when trastuzumab was being developed, what the risk of stage I HER2+ disease would be for patients. We do now, however, have a lot of data that has accumulated over the years from retrospective series of untreated patients that suggests that patients who have stage I HER2+ breast cancer are at more than just an insignificant risk of recurrence with really rates of recurrence ranging as high as 30% in some series.

And so knowing that these patients were at some risk, but maybe not as much risk as patients who had stage II or III cancers. There’s been a lot of work that has been done to try and figure out what would the appropriate systemic therapy be for patients who have stage I HER2+ disease, again since they weren’t included in the pivotal adjuvant trials.

One of the first studies to do this was the APT trial, which looked at an abbreviated chemotherapy regimen with giving just 12 weeks of paclitaxel and trastuzumab followed by nine months of trastuzumab alone to patients with stage I – predominantly stage I – HER2+ tumors. The trial found a really low event rate, so at about seven years of follow-up, the recurrence free interval was 97.5% really suggesting there are very few distant recurrences that are occurring in patients who have these smaller node-negative HER2+ cancers.

And so, while, you know, Taxol and Herceptin has certainly been a standard that many have adopted for these patients, there’s been a lot of interest in also seeing if we could even do a little better in terms of maintaining outstanding efficacy and keeping event rates low, but also trying to diminish toxicity.

And so, there was another trial that our group had run called the ATTEMPT Trial, which had randomized stage I HER2+ patients to receive T-DM1 for a year or should receive the TH regimen. This trial had found that a year of T-DM1 was associated with a very low event rate, so the three-year invasive disease-free survival was about 98%. But the trial was also really designed to compare toxicities between the two arms. So, it had another endpoint which was comparing clinically relevant toxicities, and in fact, the total rate of these toxicities was the same in each arm. There was really no difference in the overall number of clinically relevant toxicities.

But I think the challenge with those data is there are different toxicities between the two arms that really do have different implications for patients. And so, you know, one finding is that certainly the Taxol Herceptin was associated with more neuro toxicity and more infusion reactions, more alopecia. Whereas for example, T-DM1 has more early treatment discontinuations, more LFT elevations, more thrombocytopenia.

I think, you know, seeing the good efficacy from T-DM1 has led many to consider T-DM1 in some select patients. For example, a patient who may be concerned about neuro toxicity or has baseline neuropathy that may be a potentially good treatment option. But I think all that being said, we’re still working towards trying to deescalate therapy further for these patients. There are other ongoing trials, including a trial called ATTEMPT 2.0, looking at a short course of T-DM1 and then another trial called ADEPT, which is looking at no chemotherapy. In fact, just looking at dual HER2-directed therapy with endocrine therapy for stage I ER-positive HER2+ tumors.

I think again, there’s been a lot of improvement and treatment for stage I disease really allowing us to use TH or T-DM1, but a lot of work ahead of us to even try and deescalate further.

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Disclosures

Sara Tolaney, MD, has received institutional research funds and honoraria from AstraZeneca, Eli Lilly, Merck, Nektar, Novartis, Pfizer, Genenrach/Roche, Immunomedics/Gi lead, Exelixis and Brsitol-Myers Squibb.