The latest combination therapy for HER2 breast cancer _tukatinib effectively improves the survival rate of patients with brain metastasis
According to the latest results of the key phase 2 HER2CLIMB trial (NCT02614794), the combination therapy of the targeted drugs Tucatinib, trastuzumab and capecitabine continued to improve HER2 compared with trastuzumab/capecitabine monotherapy.The total survival rate (OS) of patients with positive metastatic breast cancer, and the brain metastasis status of these patients is stable or active.
Tucatinib Tucatinib New drug introduction
Tucatinib is an oral targeted drug for the HER2 protein. In vitro, the agent has been shown to inhibit the phosphorylation of HER2 and HER3, thereby inhibiting the transmission of downstream MAPK and AKT signals and cell growth. The drug also showed antitumor activity on HER2-expressed tumor cells. Tucatinib has also been found to inhibit the growth of tumors expressing HER2 in vivo. When used in combination with trastuzumab, the anti-tumor activity of the program in vitro and in vivo is higher than that of any drug alone.
Chinese name: Tucatinib
Drug name: Tucatinib
Product name: Tukysa
Manufacturer: Seattle Genetics
Tucatinib Tucatinib latest treatment data
This multinational, randomized, double-blind, placebo-controlled, actively compared, pivotal clinical trial randomized 612 patients into two groups. Patients received oral tucatinib at 300 mg twice daily, plus intravenous trastuzumab with a loading dose of 8 mg/kg on day 1 of cycle 1, followed by 6 mg/kg every 3 weeks, and oral capecitabine at 1000 mg/m² twice daily from day 1 to day 14 of each 21-day cycle (n = 410), or placebo plus trastuzumab/capecitabine (n = 202). Eligible patients had unresectable, locally advanced, or metastatic HER2-positive breast cancer and had previously received treatment with trastuzumab, pertuzumab (Perjeta), and T-DM1 (Kadcyla). Patients also had an ECOG performance status of 0 or 1 and a brain MRI at baseline. It is worth noting that patients with stable brain metastases who have received treatment, untreated metastatic patients who do not require immediate treatment, previously treated patients with progressive metastases who do not require immediate treatment, and patients without evidence of brain metastases are all eligible to participate. The primary endpoint of the trial is progression-free survival (PFS) according to RECIST v1.1 criteria and blinded independent central review (BICR). Secondary endpoints include overall survival (OS) and PFS in patients with metastases, and confirmed OS in patients with measurable disease.
The latest data presented at the 2021 San Antonio Breast Cancer Symposium showed that, after a median follow-up of 29.6 months, the median overall survival (OS) of tucatinib triple therapy was 21.6 months (95% CI, 18.1–28.5), while the OS of trastuzumab and capecitabine monotherapy was 12.5 months (95% CI, 11.2–16.9) in patients with active and stable brain metastases (n = 291; HR, 0.60; 95% CI, 0.44–0.81). In patients with active brain metastases (n = 174), the median overall survival (OS) was 21.4 months (95% CI, 18.1–28.9) with the addition of tucatinib, compared to 11.8 months (95% CI, 10.3–15.2) with trastuzumab and capecitabine alone (HR, 0.52; 95% CI, 0.36–0.77). Furthermore, in patients with stable brain metastases (n = 117), the median OS was 21.6 months (95% CI, 15.3–42.4) in the tucatinib group and 16.4 months (95% CI, 10.6–21.6) in the placebo group (HR, 0.70; 95% CI, 0.42–1.16).
Additional recent data indicate that the combination therapy improved median central nervous system (CNS) progression-free survival in patients with stable and active brain metastases compared to trastuzumab/capecitabine monotherapy, at 9.9 months (95% CI, 8.4–11.7) and 4.2 months (95% CI, 3.6–5.7), respectively (HR. 0.39; 95% CI, 0.27–0.56).
Furthermore, the median CNS-PFS was 9.6 months (95% CI, 7.6–11.1) in patients with active brain metastases, compared to 4.0 months (95% CI, 2.9–5.6) in the tucatinib and placebo groups (HR, 0.34; 95% CI, 0.22–0.54). In addition, for patients with stable brain metastases, the median CNS-PFS with tucatinib triple therapy was 13.9 months (95% CI, 9.7–24.9), compared to 5.6 months (95% CI, 3.0–unevaluable) with trastuzumab/capecitabine (HR, 0.41; 95% CI, 0.19–0.85). Regarding safety, serious adverse events (AEs) occurred in 26% of patients in the tucatinib treatment group. Serious adverse events (AEs) occurred in 2% or more of patients receiving tucatinib, including diarrhea (4%), vomiting (2.5%), nausea (2%), abdominal pain (2%), and seizures (2%). Fatal AEs, including sudden death, sepsis, dehydration, and cardiogenic shock, were reported in 2% of patients receiving tucatinib.
Reminder: The risk of breast cancer spreading to the brain is more obvious for patients with aggressive subtypes of breast cancer, including HER2-positive breast cancer. The latest analysis shows that the tucatinib regimen not only helps patients live longer, but also slows down the progress of the disease in the brain, providing a promising result for HER2-positive metastatic patients.
