Abstract Background: Treatment options for HER2 positive MBC are increasing and trastuzumab deruxtecan (T-DXd) is now used in earlier lines of treatment, having shown superiority to trastuzumab emtansine (T-DM1) in DESTINY-Breast03 and to THP in DESTINY-Breast09. Uncertainty remains on the optimal sequencing of these drugs and their impact on OS with concerns raised regarding the generalisability of reported progression free survival (PFS) and treatment attrition rates in these trials. In this series, we report treatment attrition rates and PFS for patients starting 1st line chemotherapy between 2019 and 2024. Methods: Electronic health records were searched for patients with HER2 positive advanced breast cancer starting 1st line treatment between 01/01/19 and 31/12/24. Dates to calculate PFS and OS as well as attrition rates were extracted for each line of therapy. Results: 143 women commenced treatment during the study period. Median age was 51.6 years at time of first breast cancer diagnosis and 55.2 years at time of metastatic disease. 82 patients had de-novo metastatic disease, invasive disease-free survival in the remainder was 46.6 months. Observed median PFS for THP (23.0 months) appeared comparable to the THP arms of CLEOPATRA (18.7 months)1 and DESTINY-Breast09 (26.9 months)2. T-DM1 (9.0 months) performed similarly to the EMILIA (9.6 months) study3 and better than the control arm of DESTINY-Breast03 (6.8, CI 5.6-8.2 months)4. T-DXd was used in 11 patients in the 2nd line setting and 16 patients in the 3rd line setting and in this small series performed considerably worse (11.7 months) than in DESTINY-Breast03 (28.8 months)4 and DESTINY-Breast02 (17.8 months)5, but was comparable to other real-world experience (12.3 months)6. With median follow-up of 27.6 months, 44 patients have died, and median OS has not been reached. 15 (34%) events were due to CNS progression and two (7%) patients treated with T-DXd experienced grade 5 pulmonary toxicity. Attrition rates mirrored published findings.7 In subgroup analysis, ER+ patients had a longer median PFS than ER- although this was not statistically significant (26.1 vs 19.9 months, p = 0.26). Notably, patients with HER2 2+ (ISH+) had shorter median PFS compared to those with HER2 3+ (10.5 vs 27.9 months, p = 0.0089). Conclusion: Guy’s Cancer serves one of the most ethnically diverse populations in the world. In this retrospective real-world study, 1st and 2nd line PFS was similar to published phase 3 studies. Although T-DXd appeared to perform better than T-DM1 in our population, it fell short of the outcomes seen in the DESTINY studies. However, due to the small number of patients treated with T-DXd and the short follow-up our confidence intervals are wide. High attrition rates and death from CNS disease in 1/3 of patients supports the earlier use of T-DXd in this population. Citation Format: H. Yan, M. Toki, H. Kristeleit. Clinical outcomes and treatment attrition rates of HER2 positive metastatic breast cancer (MBC) patients at a tertiary referral cancer centre in London: the Guy’s Cancer experience abstract. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS5-02-16.
Yan et al. (Tue,) studied this question.