Patients with heavily treated metastatic HER2-positive breast cancer lived significantly longer when an investigational anti-HER2 drug was added to trastuzumab (Herceptin) and chemotherapy, according to the phase II presented at the recent 2019 San Antonio Breast Cancer Symposium.
In this exclusive 乌鸦传媒 video, study author , of MD Anderson Cancer Center in Houston, and , of Mount Sinai Hospital in New York City, discuss the HER2CLIMB trial.
Following is a transcript of their remarks:
Rashmi Murthy: HER2CLIMB was a pivotal study conducted in patients with heavily pretreated metastatic HER2-positive breast cancer. This trial included patients with an active presence or history of brain metastases. The results show an improvement in progression-free survival, both in the overall population as well as the brain metastasis population, and most importantly show a benefit in overall survival.
The regimen was very well tolerated with mainly low-grade toxicities, and the most common side effects were diarrhea, which was very manageable, hand-foot syndrome, which was likely attributed to duration of exposure to capecitabine in the tucatinib arm, as well as nausea, vomiting, and fatigue. Again, all mostly low grade. This is an option that has a potential to be a new standard of care for patients who have been heavily pretreated and who have limited systemic treatment options in later lines of therapy.
Amy Tiersten: The results were pretty amazing. Overall, there was a 50% reduction in the risk of progression or death in patients who were randomized to receive the tucatinib. One super exciting thing about this trial is it's the first one that I'm aware of that allowed patients who had untreated or progressing brain metastases to enter the study, and another interesting point was that the one-year progression-free survival for the subgroup of patients who had brain metastasis was 25% versus 0% for patients who did not receive tucatinib.
I think this is excitingly enough data that this has the potential -- this regimen of trastuzumab, capecitabine, and tucatinib -- to become a standard of care, perhaps third-line regimen in this setting. There were a lot of other interesting, new HER2 agents that are being reported about, and I think it's interesting where tucatinib may fall and which line of therapy eventually. But right now, I think this regimen should become a standard third-line for patients who fit the eligibility of the protocol.
I think, as always, as things look impressive in later lines of therapy, it'll be interesting to see what we can do in terms of moving them into earlier lines of therapy, adding them to other dual, targeted antibody therapy, and of course, eventually hoping that we can cure more patients by moving some of these really exciting drugs into the adjuvant or neoadjuvant setting.
Murthy: Because of the activity of tucatinib across the blood-brain barrier with regard to treatment of brain metastases, we're also conducting an investigator-initiated trial through the Translational Breast Cancer Research Consortium to see if tucatinib has activity in the setting of leptomeningeal disease. Currently, there aren't really very good treatment options for leptomeningeal disease, and so this study is evaluating this regimen within that patient population who has very great unmet medical need. Also, there's an ongoing clinical trial looking at tucatinib versus placebo in combination with T-DM1 in either the first-line or second-line settings looking to potentially move tucatinib into earlier lines of metastatic disease treatment.