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BREAST CANCER

Brain metastases respond to neratinib plus capecitabine

Brain metastasis from HER2-positive breast cancer remains a major clinical challenge owing to the lack of approved treatments, particularly in the setting of central nervous system (CNS) recurrence after radiotherapy and/or surgery. Previous findings from cohort 1 of the phase II TBCRC 022 study demonstrated that the pan-HER tyrosine kinase inhibitor neratinib had only modest activity as monotherapy against brain metastases. Now, new data from TBCRC 022 cohorts 3A and 3B establish the efficacy of neratinib plus capecitabine against brain metastases from refractory, HER2-positive breast cancers.

Credit: S. Bradbrook/Springer Nature Limited

The phase II single-arm studies enrolled women with lapatinib-naive (cohort 3A; n = 37) or lapatinib-pretreated (cohort 3B; n = 12; closed early owing to slow accrual) disease with measurable, progressive, HER2-positive brain metastases, who received neratinib plus capecitabine during each 21-day cycle (14 days on, 7 days off). The primary end point was investigator-defined composite CNS objective response rate (ORR).

The cohort 3A composite CNS ORR was 49% (95% CI 32–66%), whereas the cohort 3B CNS ORR was 33% (95% CI 10–65%). In cohorts 3A and 3B, median progression-free survival was 5.5 and 3.1 months, respectively, and median overall survival was 13.3 and 15.1 months, respectively.

No grade ≥4 adverse events occurred. “Grade 2 and 3 diarrhoea was the most common side effect (29% in cohorts 3A and 3B combined) and we asked patients to take preventative medication for this when they started the trial,” explains lead investigator Rachel Freedman. The other most frequent grade 2 and 3 adverse events were nausea, vomiting and fatigue.

new data … establish the efficacy of neratinib plus capecitabine against brain metastases from refractory, HER2-positive breast cancers

These findings suggest that the efficacy of neratinib is enhanced by chemotherapy in the setting of HER2-positive brain metastases. “Future studies are looking at other combinations in this setting, such as T-DM1–neratinib,” concludes Freedman.

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Correspondence to Conor A. Bradley.

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Bradley, C.A. Brain metastases respond to neratinib plus capecitabine. Nat Rev Clin Oncol 16, 336 (2019). https://doi.org/10.1038/s41571-019-0207-3

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