The addition of tucatinib to trastuzumab and capecitabine in patients with HER2-positive metastatic breast cancer with and without brain metastases resulted in statistically significant and clinically meaningful improvements in progression-free and overall survival.
The addition of tucatinib (Tukysa) to trastuzumab (Herceptin) and capecitabine (Xeloda) in patients with HER2-positive metastatic breast cancer with and without brain metastases resulted in statistically significant and clinically meaningful improvements in progression-free survival (PFS) and overall survival (OS), according to results from the HER2CLIMB that were presented during the 2020 ESMO Virtual Congress.
Notably, this combination has been approved by the FDA based on results from the primary analysis of this trial for the treatment of patients with and without brain metastases who have received 1 or more prior anti-HER2-based regimens in the metastatic setting.
“Taken together, this regimen not only provides meaningful clinical activity, but also maintains quality of life in patients with or without brain metastases,” Volkmar Mueller, head of the Oncology Outpatient Clinic at the University Medical Center Hamburg-Eppendorf in Hamburg, Germany, said in a virtual presentation during the meeting.
The pivotal, randomized trial of tucatinib in combination with trastuzumab and capecitabine versus placebo in combination with trastuzumab and capecitabine enrolled patients with HER2-positive metastatic breast cancer who had received prior treatment with trastuzumab, pertuzumab (Perjeta), and T-DM1, had an ECOG performance status of 0 or 1, and who had a brain MRI at baseline. Including patients who were previously untreated, treated stable, and treated and progressing, 48% of patients had brain metastases at baseline.
Overall, 410 patients were randomized to the tucatinib arm and 202 to the placebo arm. Of the total cohort of 612 patients, 330 had data available for health-related quality of life (HRQoL) analyses, including 217 patients in the tucatinib arm and 113 patients in the placebo arm.
In patients treated with the tucatinib combination, 2-year OS was 45% (95% CI, 37-53) compared to 27% in the placebo combination arm (95% CI, 16-39). Moreover, median OS for the tucatinib arm was 21.9 months (95% CI, 18.3-31.0) versus 17.4 months in the placebo arm (95% CI, 13.6-19.9). In the total cohort of 612 patients, risk of death was reduced by 34% (95% CI, 0.50-0.88; P = .005).
The median duration of exposure was 7.3 months for those treated with the tucatinib combination (<0.1-35.1) and 4.4 months for those treated with the placebo combination (<0.1-24.0).
The primary end point of PFS by blinded independent central review was assessed in the first 480 patients enrolled. Overall, risk of progression or death was reduced by 46% (95% CI, 0.42-0.71; P < 0.001). Specifically in patients with brain metastases (n = 291), risk of progression or death was reduced by 52% (95% CI, 0.34-0.69; P < .001).
Notably though, benefit was observed in patients both with and without brain metastases.
Researchers also assessed HRQoL with protocol version 7, using the EQ-5D-5L which includes an EQ visual analog scale (VAS) and descriptive system (EQ-5D) of 5 health dimensions, including mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension has 5 levels which consist of no, slight, moderate, severe, or extreme problems.
Across all 5 EQ-5D-5L domains, the majority of patients in both arms reported only slight or no problems. Moreover, moderate, severe, or extreme problems that were reported were low and similar between the treatment arms. No clinically meaningful differences in HRQoL were seen between the 2 arms.
Overall, mobility and usual activities were maintained by patients throughout the course of treatment. There was also no change in pain and self-care categories reported throughout the treatment course. Further, there was no change in the anxiety/depression category throughout the course of treatment.
In addition, mean EQ-5D-5L VAS scores were similar between patients treated with the tucatinib combination and those treated with the placebo combination and were also stable throughout the duration of therapy. Decline on EQ-5D-5L domains and VAS scores were also not observed while patients were on therapy.
With regard to safety, the addition of tucatinib did not increase the percentage of patients who required hospitalization. Treatment-related adverse events (AEs) which resulted in hospitalization in ≥1% of patients in the tucatinib arm included diarrhea (3%), vomiting (2%), seizure (2%), and dyspnea (1%). All other events that led to hospitalization were less than 1%.