“Overall survival [in stable patients] numerically favored tucatinib to a small extent, but this did not reach statistical significance, albeit in a relatively small number of patients,” Dr. Lin said in her presentation.
Between-arm differences were significant in the 174 patients who entered the trial with active brain metastases, which refers to those that were either known but untreated, newly discovered on baseline MRI, or progressed after treatment. At 1 year, 35% of these patients in the tucatinib arm were still alive and free of CNS progression; however, there were no such patients in the placebo arm.
The median CNS PFS among patients with active brain metastases at study entrance was 9.5 months with tucatinib versus 4.1 months in the placebo arm (P < .0001). The median overall survival was 20.7 months and 11.6 months, respectively (P = .004).
Intracranial response was confirmed by MRI in 47% of tucatinib-treated patients with active brain metastasis at baseline versus 20% of patients on placebo (P = .03).
Re-treatment after progression
Thirty subjects – 21 on tucatinib and 9 on placebo – returned to their study arm after radiation for brain lesion progression.
The risk of second progression or death was reduced 67% when patients restarted tucatinib instead of placebo.
The median time from first CNS progression to a second progression or death was 7.6 months with tucatinib versus 3.1 months with placebo (P = .02).
“The data suggest a potential benefit for continuation of tucatinib beyond first isolated CNS progression,” Dr. Lin said.
As for why tucatinib helps, she and her colleagues speculated that, because tyrosine kinase inhibitors are small molecules, they can cross the blood brain barrier and effectively treat CNS lesions, while larger, antibody-based anti-HER2 agents, such as trastuzumab and pertuzumab, cannot.
Study entry required prior treatment with trastuzumab, pertuzumab, and ado-trastuzumab emtansine, as well as an Eastern Cooperative Oncology Group performance score of 0 or 1. More than 99% of the subjects in the analysis were women, and the median age was 52 years.
The treatment groups were well balanced. A bit over half of the subjects in both arms were in North America, and 57% were estrogen and/or progesterone receptor positive. Adverse events were reported previously.
This research was funded by tucatinib’s maker, Seattle Genetics. Dr. Lin and colleagues disclosed financial relationships with Seattle Genetics, including employment. Dr. Tiersten reported no relevant conflicts of interest.
SOURCE: Lin NU et al. ASCO 2020, Abstract 1005; J Clin Oncol. 2020 May 29. doi: 10.1200/JCO.20.00775