- Neratinib plus capecitabine is associated with a 33% to 49% objective response rate (ORR) against brain metastases in patients with and without prior lapatinib therapy, respectively, for human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (mBCa).
Why this matters
- 50% of patients with HER2+ mBCa develop brain metastases.
- Two phase 2, open-label, single-group cohorts of HER2+ mBCa with brain metastases who were enrolled in TBCRC 022, with 1 cohort comprising lapatinib-naive patients (n=37) and the other cohort lapatinib-experienced (n=12) patients. Both cohorts were given neratinib 240 mg orally once per day plus 750 mg/m2capecitabine 2×/day for 14 days, then 7 days off.
- ORR required ≥50% reduction in the sum of target central nervous system (CNS) lesion volumes without progression of nontarget lesions, new lesions, escalating steroids, progressive neurologic signs or symptoms, or non-CNS progression.
- Funding: Puma Biotechnology; several foundations.
- Lapatinib-naive patients: ORR, 49% (95% CI, 32%-66%); median PFS, 5.5 months; median OS, 13.3 months.
- Lapatinib-experienced patients: ORR, 33% (95% CI, 10%-65%); median PFS, 3.1 months; median OS, 15.1 months.
- The most common toxicity was diarrhea (29%), despite prophylaxis.
- Open-label, observational designs.