Author: By Lynda Williams, Senior medwireNews Reporter
medwireNews: HER2CLIMB trial results indicate that HER2-positive metastatic breast cancer survival may be improved by the addition of the oral HER2 tyrosine kinase inhibitor (TKI) tucatinib to trastuzumab plus capecitabine.
The phase II double-blind randomised study included 612 patients who had previously received a median of three lines of treatment for metastatic disease including trastuzumab, pertuzumab and trastuzumab emtansine, delegates were told at the San Antonio Breast Cancer Symposium in Texas, USA.
The primary endpoint of progression-free survival (PFS) at 1 year was determined for the first 480 patients and was significantly higher among the 320 patients given tucatinib 300 mg twice daily alongside trastuzumab and capecitabine than the 160 patients who instead received placebo plus trastuzumab and capecitabine, at 33.1% versus 12.3% and a hazard ratio of 0.54 in favour of the TKI.
Median PFS duration in the tucatinib and placebo arms was 7.8 months and 5.6 months, respectively, while overall survival at 2 years was achieved by 44.9% and 26.6%, giving a significant hazard ratio (HR) for death of 0.66, again favouring tucatinib, said presenting author Rashi Murthy, from the University of Texas MD Anderson Cancer Center in Houston, USA.
Approximately 45% of patients had a history of, or had current brain metastases at baseline and again the 1-year PFS rate was significantly higher with tucatinib than placebo, at 24.9% versus 0% and a HR of 0.48. Median PFS duration in the two arms was 7.6 and 5.4 months, respectively.
Safety analysis showed that diarrhoea was the most common event in both treatment arms but tucatinib-treated patients were more likely than the placebo group to experience grade 1 (43.3 vs 32.0%), grade 2 (24.8 vs 12.7%) and grade 3 diarrhoea (12.9 vs 8.6%). Grade 3 elevated aspartate and alanine aminotransferase (4.5 vs 0.5% and 5.4 vs 0.5%, respectively) were also more common with the tucatinib regimen.
“[T]ucatinib plus trastuzumab and capecitabine is an active combination in heavily pretreated patients with HER2-positive metastatic breast cancer, including those with previously untreated, treated and stable, or treated and progressing brain metastases”, the HER2CLIMB investigators conclude in their simultaneous publication in The New England Journal of Medicine.
Murthy RK, Loi S, Okines A, et al. Tucatinib, trastuzumab, and capecitabine for HER2-positive metastatic breast cancer. N Engl J Med; Advance online publication 11 December 2019. DOI: 10.1056/NEJMoa1914609
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