Post-Conference Perspectives: Optimizing the Management of HER2+ Metastatic Breast Cancer - Episode 4

Emerging Data for the Treatment of HER2+ mBC

Transcript:

Sarah A. Hurvitz, MD: I was very active on the HER2CLIMB study, and it was a blinded trial so it’s not entirely clear which patients were receiving placebo or tucatinib, which is somewhat of a good thing. If you can’t tell what agent your patient’s been assigned to because their toxicity profile doesn’t look much different, I think that’s a good early indicator. Certainly the data from HER2CLIMB do indicate the safety profile is relatively good with tucatinib.

I would project that it will probably be made available. I would suspect the FDA is going to be quite compelled by the OS [overall survival] and PFS [progression-free survival] data as well as PFS data in patients with CNS [central nervous system] metastases and give it a regulatory approval. I am hoping I will have it available for my patients who have HER2-positive metastatic breast cancer. This trial was conducted in the later-line setting. The median number of therapies that patients had received in the metastatic setting was around 3 in this trial. That’s probably where we’re going to have the most data to support its use.

A question is going to come up, however. If we have a patient who, for example, is on maintenance HP [hesperetin] in the first-line setting and developed CNS metastases, would that compel one to switch them to tucatinib, capecitabine, trastuzumab given the CNS activity? I don’t know the answer to that today. I think I might be tempted to do that in spite of the ASCO [American Society of Clinical Oncology] guidelines telling us we should locally regionally treat the CNS metastases and continue HP. I might be compelled or tempted to switch over to tucatinib. I’m looking forward to the design and implementation of clinical trials that will look at moving tucatinib up earlier and look at whether we can prevent the development of CNS metastases in HER2-positivie breast cancer.

Not only were the tucatinib data in HER2CLIMB revealed at the 2019 San Antonio Breast Cancer Symposium, but exciting data relating to trastuzumab deruxtecan were also unveiled. This is a phase II single-arm clinical trial called DESTINY-Breast01. In this trial, about 180 patients received the DS-8201, or trastuzumab deruxtecan. These were heavily pretreated patients. The median number of prior lines of therapy was 6, and the objective response rate was outstanding. It was over 60% with 6% of patients achieving a complete response.

The median PFS was over 16 months. To think that an agent would have this level of activity in that late-line setting is incredibly exciting. I think we’re going to be seeing that agent move up into earlier lines as well.

The treatment of HER2+ metastatic breast cancer is rapidly evolving. My advice is to look for studies to enroll your patients in whenever and wherever possible because we’re seeing these very exciting agents that have demonstrated such profound efficacy in late line move up now into large clinical trials in earlier lines of therapy—our hope being that we’ll push the needle on long-term durable remission in this disease subtype. It’s also important to stay apprised of the news when it comes out. It seems like almost quarterly now we’re having big updates from congresses where data are presented that lead to real practice-changing factors. To be able to keep apprised of the data by going online and doing CME [continuing medical education] lectures is I think critical now to convey these new findings to our practices with patients.

Transcript Edited for Clarity