Neratinib–Capecitabine Combo Active Against Breast Cancer Brain Metastases
Supplementary study data support the use of neratinib plus capecitabine in the treatment of patients with refractory, HER2-positive breast cancer brain metastases, and further demonstrates that chemotherapy enhances the efficacy of HER2-directed therapy in the brain (J Clin Oncol. 2019 March 12. Epub ahead of print).
“Evidence-based treatments for metastatic,…HER2-positive breast cancer to the CNS are limited,” explained Rachel A. Freedman, MD, MPH, 1Dana-Farber Cancer Institute, Boston, Massachusetts, and colleagues.
Having previously reported on the modest activity of neratinib used as a single-agent for the treatment of HER2-positive breast cancer brain metastases, Dr Freedman and colleagues now share updated findings from additional study cohorts.
A total of 49 patients with progressive, HER2-positive brain metastases (92% after receiving CNS surgery and/or radiotherapy) were enrolled in the trial and given neratinib 240 mg once daily plus capecitabine 750 mg/m2 twice daily for 2 weeks, then 1 week off.
They were separated into 2 cohorts based on previous exposure to lapatinib therapy; cohort 3A included 37 lapatinib-naïve patients, and cohort 3B included 12 lapatinib-treated patients.
According to Dr Freedman and colleagues, the combination of neratinib and capecitabine would be considered “promising” if ≥9 patients in cohort 3A or ≥3 patients in cohort 3B had CNS objective response rates (ORR).
The primary end point of the study was composite CNS ORR in each cohort, requiring a reduction of ≥50% in the sum of target CNS lesion volumes without progression of nontarget lesions, new lesions, escalating steroids, progressive neurologic signs or symptoms, or nonCNS progression.
Ultimately, the composite CNS ORR was 49% (95% confidence interval [CI], 32%-66%) in cohort 3A and 33% (95% CI, 10%-65%) in cohort 3B. The median progression-free survival was 5.5 and 3.1 months in each cohort, respectively, and median survival was 13.3 and 15.1 months, respectively.
The most frequently reported grade 3 toxicity, occurring in 29% of patients in cohorts 3A and 3B, was diarrhea.
“Neratinib plus capecitabine is active against refractory, HER2-positive breast cancer brain metastases, adding additional evidence that the efficacy of HER2-directed therapy in the brain is enhanced by chemotherapy,” Dr Freedman and colleagues said.
“For optimal tolerance, efforts to minimize diarrhea are warranted,” they concluded.—Hina Khaliq