Dr McAndrew on the Impact of the KATHERINE Trial in HER2+ Breast Cancer

Nicholas P. McAndrew, MD, MSCE, health sciences clinical assistant professor, Hematology/Oncology, University of California, Los Angeles (UCLA), UCLA Health, discusses the impact of the phase 3 KATHERINE trial (NCT01772472) in patients with HER2-positive breast cancer.

McAndrew says he found it important to provide an update on the KATHERINE trial during an OncLive® State of the Science Summit™ on breast cancer. McAndrew explains that this phase 3 study has had an immediate impact on clinical practice. However, early-stage breast cancer studies are characterized by their long-term follow up data, which offer continuous insights for oncologists over the years, he expands. The significance of the KATHERINE trial lies in establishing a clinically meaningful rationale for neoadjuvant therapy in patients with HER2-positive breast cancer, particularly for patients with high-risk disease who may benefit from post-neoadjuvant therapy intensification, McAndrew elucidates. 

KATHERINE observed ado-trastuzumab emtansine (T-DM1; Kadcyla) vs trastuzumab (Herceptin) in patients with HER2-positive early breast cancer who had undergone neoadjuvant chemotherapy but did not achieve a pathologic complete response and instead maintained residual disease post-neoadjuvant chemotherapy, he continues. Previous analyses in this setting had indicated that these patients face a worse prognosis, which is marked by inferior disease-free survival (DFS). However, the initial analysis of KATHERINE revealed an approximate 11% benefit in 3-year invasive DFS (IDFS) with T-DM1 vs trastuzumab, translating to a notable 50% reduction in the risk of recurrence, McAndrew says.

At the 2023 San Antonio Breast Cancer Symposium, investigators presented an updated 7-year analysis with a median follow-up of 8.4 years, which offered a more comprehensive evaluation of the trial. The IDFS benefit with T-DM1 increased to 13.7%, with a relative risk reduction of 46%, he explains. This extended follow up reinforces that the observed benefit with T-DM1 is not merely a delay in metastases; rather, it appears to be a sustained and meaningful IDFS advantage over time. This further emphasizes the importance of adopting neoadjuvant T-DM1 in the management of HER2-positive breast cancer, McAndrew concludes.