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

In Ah Kim, Kathryn A. Winter, Paul W. Sperduto, Jennifer F. De Los Santos, David M. Peereboom, Tomi Ogunleye, Daniel Boulter, Joel M. Fritz, Kwan Ho Cho, Kyung Hwan Shin, Imran Zoberi, Serah Choi, Joshua D. Palmer, Ben Liem, Yong Bae Kim, Bethany M. Anderson, Anupama W. Thakrar, Thierry M. Muanza, Michelle M. Kim, Doo Ho ChoiMinesh P. Mehta, Julia R. White

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

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-specific 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 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.

Original languageEnglish
Pages (from-to)1391-1401
Number of pages11
JournalInternational Journal of Radiation Oncology Biology Physics
Volume118
Issue number5
DOIs
StatePublished - Apr 1 2024

Fingerprint

Dive into the research topics of 'Concurrent Lapatinib With Brain Radiation Therapy in Patients With HER2+ Breast Cancer With Brain Metastases: NRG Oncology–KROG/RTOG 1119 Phase 2 Randomized Trial'. Together they form a unique fingerprint.

Cite this