Concurrent Lapatinib With Brain Radiation Therapy in Patients With HER2+Breast Cancer With Brain Metastases: NRG Oncology - KROG/ RTOG 1119 Phase 2 Randomized Trial

Purpose: Lapatinib plus whole brain radiation therapy (WBRT) or stereotactic radiosurgery (SRS) was hypothesized to improve the 12 -week intracranial complete response (CR) rate compared with either option of radiation therapy (RT) alone for patients with brain metastases (BM) from human epidermal growth factor receptor 2 - positive (HER2+) breast cancer. Methods and Materials: This study included patients with HER2+ breast cancer with >= 1 measurable, unirradiated BM. Patients were randomized to WBRT (37.5 Gy/3 wk)/SRS (size -based dosing) +/- concurrent lapatinib (1000 mg daily for 6 weeks). Secondary endpoints included objective response rate (ORR), lesion -speci fi c response, central nervous system progression -free survival, and overall survival. Results: From July 2012 to September 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 = .97), or ORR at 12 weeks. At 4 weeks, RT + lapatinib showed higher ORR (55% vs 42%). Higher graded prognostic assessment and <= 10 lesions were associated with higher 12 -week ORR. Grade 3 and 4 adverse event rates were 8% and 0% for RT and 28% and 6% for RT + lapatinib. Conclusions: The addition of 6 weeks of concomitant lapatinib to WBRT/SRS did not improve the primary endpoint of 12week CR rate or 12 -week ORR. Adding lapatinib to WBRT/SRS showed improvement of 4 -week ORR, suggesting a short-term bene fi t from concomitant therapy. (c) 2023 Elsevier Inc. All rights reserved.