medwireNews: The second-generation irreversible pan-HER tyrosine kinase inhibitor pyrotinib in combination with capecitabine shows promising activity against brain metastases in women with HER2-positive metastatic breast cancer, say researchers.
The combination was particularly effective for women who were radiotherapy-naïve and was not associated with any unexpected adverse events, report Min Yan (The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, China) and co-authors in The Lancet Oncology.
The findings are a result of the multicenter phase 2 PERMEATE trial, which enrolled 59 Chinese women with HER2-positive breast cancer and brain metastases who were radiotherapy-naïve and 19 who had progressive central nervous system (CNS) disease after radiotherapy.
The women in both groups were treated with pyrotinib 400 mg once daily without breaks and capecitabine 1000 mg/m2 twice daily in a 2 weeks on, 1 week off regimen until disease progression or unacceptable toxicity.
During a median 15.7 months of follow-up, 11.9% of radiotherapy-naïve participants had an investigator-assessed complete intracranial response and 62.7% had a partial response, giving a CNS objective response rate (ORR) of 74.6%.
For those with prior radiotherapy exposure, the complete response rate was 5.2% and the partial response rate was 36.8%, giving a CNS ORR of 42.1%.
The median times to a CNS response in the women without and with prior radiotherapy were 1.3 and 1.5 months, respectively, and the corresponding median response durations were 12.5 and 7.7 months.
In addition, 70.4% of 27 patients with measurable extracranial disease in the radiotherapy-naïve cohort had an objective response, as did two of four patients in the radiotherapy-exposed cohort.
For the radiotherapy-naïve participants overall, median progression-free survival was 11.3 months, while for those with radiotherapy exposure it was 5.6 months. Median overall survival was not reached in either cohort.
Yan and team also report that the adverse events they observed “were consistent with the known toxicity profile of pyrotinib plus capecitabine.”
The most common grade 3 or worse treatment-emergent adverse event was diarrhea, which occurred in 24% and 21% of women without and with previous radiotherapy, respectively, and was reversible with dose adjustments and antidiarrheal medication.
There were two (3%) serious adverse events in the radiotherapy-naïve cohort (grade 4 anemia and grade 3 abdominal distension) and three (16%) in the radiotherapy exposed cohort (grade 3 anemia, grade 3 increased alanine aminotransferase, and grade 2 vomiting), but no treatment-related deaths in either group.
Yan et al conclude that “pyrotinib plus capecitabine is well tolerated and active for both intracranial and extracranial lesions, especially for patients with radiotherapy-naïve brain metastases.”
They add that their findings were similar to those of the PHOEBE and PHENIX trials and suggest that the combination of pyrotinib plus capecitabine “deserves further validation in a randomised, controlled trial.”
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