The HER2CLIMB Study in HER2+ MBC
The significance of the HER2CLIMB study of tucatinib in combination with capecitabine and trastuzumab as treatment for patients with HER2-positive metastatic breast cancer.
EP: 1.Current Standard of Care for HER2+ MBC
EP: 2.The HER2CLIMB Study in HER2+ MBC
EP: 3.Implications of DESTINY-Breast01 in HER2+ MBC
EP: 4.Updates in HER2+ MBC: The NALA and SOPHIA Trials
EP: 5.Safety Profiles of Systemic Therapies for HER2+ MBC
EP: 6.Subcutaneous Therapy for HER2+ Breast Cancer
EP: 7.Individualized Treatment Decisions for HER2+ Breast Cancer
EP: 8.Relapsed/Refractory HER2+ MBC Treatment Decisions
EP: 9.Brain Metastasis in HER2+ MBC
EP: 10.Treatment Options for HER2+ MBC With Brain Metastasis
EP: 11.Case Scenario: 55-Year-Old Woman With HER2+ MBC and Brain Metastasis
EP: 12.Gaps in Treatment for HER2+ MBC With Brain Metastasis
EP: 13.Frontline Therapy for Triple-Positive Breast Cancer
EP: 14.Emerging Combinations for Triple-Positive Breast Cancer
EP: 15.Immunotherapy for HER2+ Breast Cancer
EP: 16.Emerging Therapies for HER2+ MBC
EP: 17.Using Systemic Therapy to Treat HER2+ Breast Cancer
Lisa A. Carey, MD, FASCO: Why don’t we move to talking about some of the newer drugs? I think you guys are already jumping into this embarrassment of riches that is HER2-positive breast cancer therapy, which is a wonderful thing for our patients. There have been several important trials that have rapidly changed the landscape of FDA-approved drugs. V.K., because you have the talking stick, let’s talk about HER2CLIMB and the findings there. How do you think that’s going to change how we approach it in the future?
Vijayakrishna Gadi, MD, PhD: The drug involved in this study is called tucatinib [Tukysa]. It’s a tyrosine kinase inhibitor, it’s very HER2-specific, and it doesn’t bind to the HER1 protein that well. It also binds tightly and doesn’t let go, so there’s some thought that once it’s bound, receptor-mediated endocytosis occurs and causes clearance of the receptor from the surface. In this study, they combine it with capecitabine [Xeloda] and trastuzumab—which is also injected in the placebo arm without the tucatinib. It was a randomized controlled trial—2:1 ratio randomization—of about 600 patients. Half the patients had brain metastases and of the patients with the brain metastases, a large fraction of them had untreated and progressing brain metastases. This is the first study of a large size to randomize and study such a patient cohort. It was a big risk in some regards, but they were rewarded.
The study was large enough where the primary end point was PFS [progression-free survival], but they had multiple secondary end points—including OS [overall survival] and PFS—specifically in patients with brain metastases. Suffice to say that they met all those end points and some more. The study was, in my opinion, wildly positive. Not only did they push median survivals out—median OS, median PFS, etc—but they hit landmarks. When you follow those curves along the way and start looking at landmarks at 12 months, 18 months, etc, the curves stay apart and are meaningfully different at those time points. This seems like a not-so-gentle push, but some patients may see some long-term benefits from this.
Just to focus on specific aspects, a lot of folks have characterized tucatinib as a brain metastases drug, but it’s very active in patients who have systemic disease outside the central nervous system. Even in the folks with the brain metastases, you see good response rates there, and OS in specific subpopulations as well. There’s a lot of exploratory analysis and lots to unpack in this study, but overall, this is a meaningful advance for our patients.
Lisa A. Carey, MD, FASCO: I completely agree. Of course, it does commit you to the tucatinib-capecitabine-trastuzumab regimen, and it’s being actively looked at in other settings. I’d like to point out Lee Schwartzberg’s comment earlier. There’s a trial that the Alliance for Clinical Trials in Oncology is running called Compass HER2 RD [residual disease], which is looking at adding tucatinib to T-DM1 [trastuzumab emtansine] in residual disease after neoadjuvant therapy. That trial is open and enrolling now. As we start moving things into the early setting, we have to reconfigure the jigsaw puzzle that is metastatic disease.
Transcript Edited for Clarity
