Erika P. Hamilton, MD, director of the Breast Cancer and Gynecologic Cancer Research Program and principal investigator at the Sarah Cannon Research Institute, discusses updated data from the phase 2 HER2CLIMB trial examining tucatinib (Tukysa) in patients with HER2-positive breast cancer and brain metastases.
Based on data from the phase 3 HER2CLIMB trial, tucatinib received regulatory approval from the FDA, says Hamilton. This trial randomized patients to receive either capecitabine, trastuzumab (Herceptin), and placebo or capecitabine, trastuzumab, and tucatinib. For many of these patients, this was their third line of therapy; they had already received prior treatment with trastuzumab, pertuzumab (Perjeta), and ado-trastuzumab emtansine (T-DM1; Kadcyla). Those who received tucatinib experienced progression-free survival (PFS) and overall survival (OS) benefit, as well as a favorable overall response rate; moreover, patients with brain metastases also experienced a PFS benefit, says Hamilton.
Updated data presented during the 2020 ASCO Virtual Scientific Program focused on patients with brain metastases. Here, patients with brain metastases were grouped into 2 categories: active, defined as untreated or treated and progressive, or stable, defined as inactive or stable and treated. HER2CLIMB was different from other trials that have been done in that it not only permitted patients with stable, treated brain metastases to enroll; those with untreated, asymptomatic brain metastases or treated and progressive brain metastases were also able to participate, Hamilton adds.
In this subgroup, 117 patients had treated, stable brain metastases and 174 patients had active metastases. In patients with active brain metastases, an improvement in PFS was observed in the tucatinib arm versus the control arm, at 9.5 months versus 4.1 months, respectively. An improvement in OS was also observed with tucatinib, at 20.7 months versus 11.6 months with the control regimen. In a challenging subset of patients with aggressive disease and active brain metastases, these data were incredibly encouraging, according to Hamilton.
Most of the adverse effects (AEs) seen with tucatinib come from the backbone of capecitabine. The most common AE was diarrhea followed by hand-foot-syndrome. Liver function abnormalities should also be monitored; however, these cases are usually symptomatic and can be managed with dose holds or reductions, concludes Hamilton.