Abstract P1-11-19: A real-world evidence study of treatment patterns in patients with HER2-positive metastatic breast cancer who have received at least 2-lines of therapy

Abstract Background. Standard-of-care treatment for HER2-positive metastatic breast cancer (HER2+ mBC) patients has traditionally included targeted therapies such as trastuzumab and/or pertuzumab in first line (1L) and ado-trastuzumab emtansine (T-DM1) in the second line (2L). In 2021, fam-trastuzumab deruxtecan-nxki (T-DXd, Enhertu®) was approved following DESTINY-Breast 03 trial results, demonstrating a significant reduction in the risk of progression compared to T-DM1 in 2L. Contemporary data on treatment patterns and clinical outcomes for HER2+ mBC patients after their 1L therapy in a real-world setting is limited and would help understand whether all eligible patients receive optimal and timely targeted therapies. This study aimed to report 2L treatment patterns and outcomes among HER2+ mBC patients in the United States (US). Methods. Adult HER2+ mBC patients with ≥2 lines of therapy were identified from the Syapse Learning Health Network (LHN) database; a longitudinal US oncology database integrating data from community health systems, labs and other external sources. Included patients initiated 2L treatment for metastatic disease between January 2014-February 2021 (index date), allowing for 12-months of follow-up. Descriptive statistics for patient characteristics, treatment patterns including prior metastatic treatments, time to treatment discontinuation (TTD), and reasons for 2L discontinuation were reported. Results. Of the 15,241 breast cancer patients in the LHN with abstracted data, 312 HER2+ mBC patients received ≥2L treatment. The patients were mostly White (69%) or African American (21%), median age of 59 years (interquartile range [IQR], 50-66) at start of 2L. The African American population was typically diagnosed young (median age 50 [IQR, 44-61] vs. 54 [IQR, 46-62] years) with stage IV disease at initial diagnosis (69% vs 62%) versus Whites. Majority of the 312 patients had stage IV disease at initial diagnosis (62%); most common sites of metastasis at mBC diagnosis were bone (52%), distant lymph node(s) (38%), liver (36%) and brain (10%). The median length of follow-up was 22 months (IQR, 13-37), 54% had initiated their 2L therapy since 2018. Majority of the 312 patients had received a trastuzumab-based (T-based) regimen in 1L (78%). Among the 312 patients, 37% had received only 2 lines of therapy in the metastatic setting, 28% received 3 and 35% received ≥4 lines of therapy. In 2L, 89% of the 312 patients received a HER2-targeted treatment (monotherapy or combination); the most frequent 2L regimens included T-DM1 monotherapy (29%), trastuzumab/pertuzumab/taxane (10%) and T-DM1/trastuzumab (8%). Subsequently, 197 of the 312 patients (63%) received 3L therapy. Among these 197 patients, T-DM1 monotherapy (19%), T-DXd monotherapy (10%) and capecitabine/lapatinib (8%) were the most frequently reported 3L regimens. Around 88% (n=274) of the 312 patients discontinued their 2L therapy. Median TTD of 2L from index date was 7.2 months (95% CI, 6.5-8.9); median TTD was 10.6 months (95% CI, 7.4-14.0) among a sub-group of patients who received a T-based regimen in their 2L (N=116). Approximately 47% of patients discontinued their 2L regimen due to progression/worsening of cancer, 17% discontinued from intolerance/toxicity in the absence of progression. Conclusions. This study suggests the treatment trajectory of US HER2+ mBC patients is variable in the real world clinical practice. Approximately two-thirds of the 2L patients had to receive a subsequent therapy and disease progression was the most common reason for 2L treatment discontinuation, reflecting a remaining need to improve outcomes for patients in 2L HER2+ disease. Citation Format: Della Varghese, Giovanna I. Cruz, Colden Johanson, Liz Toland, Miguel Miranda, Eleanor C. Faherty, David Harland, Henry G. Kaplan. A real-world evidence study of treatment patterns in patients with HER2-positive metastatic breast cancer who have received at least 2-lines of therapy [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P1-11-19.