PURPOSE : Lapatinib plus whole brain radiotherapy (WBRT) or Stereotactic Radiosurgery (SRS) was hypothesized to improve the 12-week intracranial complete response (CR) rate compared to either option of radiotherapy (RT) alone for patients with brain metastases from human epidermal growth factor receptor 2 (HER2)-positive breast cancer.

METHODS : This study included HER2+ breast cancer patients with ≥1 measurable, unirradiated BM. Patients were randomized to WBRT (37.5 Gy/3 weeks)/ SRS (size-based dosing) +/- concurrent lapatinib (1000 mg daily for 6 weeks). Secondary endpoints include objective response rate (ORR), lesion-specific response, central nervous system progression-free survival (CNS PFS), and overall survival.

RESULTS : From 7/2012 to 9/2019, 143 patients were randomized, with 116 analyzable for the primary endpoint. RT+lapatinib did not improve 12-week CR (0% vs 6% for RT alone, 1-sided p=0.97), or ORR at 12 weeks. At 4 weeks, RT+lapatinib showed higher ORR (55% vs. 42%). Higher graded prognostic assessment (GPA) and ≤10 lesions were associated with higher 12-week ORR. Grade 3 and 4 adverse events rates were 8% and 0% for RT and 28% and 6% for RT+lapatinib.

CONCLUSION : The addition of 6 weeks of concomitant lapatinib to WBRT/SRS did not improve the primary endpoint of 12-week CR rate or 12-week ORR. Adding lapatinib to WBRT/SRS showed improvement of 4-week ORR suggesting a short-term benefit from concomitant therapy.