The treatment of human epidermal growth factor receptor 2 positive (HER2+) metastatic breast cancer (mBC) has changed dramatically with the introduction of several new anti-HER2 agents. In 2021, Trastuzumab Deruxtecan (TDXd) was approved in the UK for treating HER2+ mBC in the third line setting. Our objective was to examine the efficacy and tolerability of TDXd in a real-world UK patient population.
Data for HER2+ mBC treated with TDXd were collected from 17 UK hospitals between December 2019 and January 2023. Clinical and demographic data were collected from medical and pharmacy records, including radiological response, the rate of dose reduction or discontinuation of TDXd, including whether this was related to interstitial lung disease (ILD).
135 HER2+ mBC patients were treated with TDXd. 36% had de novo metastatic disease. The median age at TDXd initiation was 55 years (range 29-85) with a median treatment duration of 9 cycles (range 1-28). At TDXd initiation, the median number of previous metastatic lines of treatment was 2 (range 0-7). 88% patients had visceral disease. 12 patients (9%) were initiated on a reduced dose and 50 further patients (37%) required at least one dose reduction. 152 treatment breaks were given to 83 patients (61%) due to: infection or neutropaenia (n=28), other toxicity (n=53), ILD investigation (n=22), patient request (n=41), other concurrent illness (n=7) and cardiac investigation (n=1). At data cut-off, 74 patients (55%) had discontinued TDXd treatment due to: disease progression (n=52), ILD (n=9), other drug toxicity (n=9) and patient choice (n=4). 13 patients have not had imaging to assess radiological response to TDXd: 5 awaiting first scan, and 8 progressed clinically. Best radiological response in the remaining 122 patients was: complete response in 5 (4%), partial response in 79 (65%), stable disease in 26 (21%) and progressive disease in 12 (10%).
The dose of TDXd was reduced in 25% of patients on the DB02 clinical trial; in this real-world data set the proportion of patients requiring a dose reduction was significantly higher at 37%. Data collection is ongoing in a larger cohort with longer follow up to better inform progression free survival in this real-world population.
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S. Frank: Financial Interests, Institutional, Invited Speaker: Amgen, AstraZeneca, Chugai, Eisai, Eli Lilly, Gilead, Merck, Mundipharma, Novartis, Pfizer; Financial Interests, Institutional, Advisory Board: Roche, Seagen, Amgen, AstraZeneca, Eli Lilly; Financial Interests, Institutional, Sponsor/Funding: Daiichi Sankyo. A.A. Konstantis: Financial Interests, Institutional, Invited Speaker: Novartis, Roche, Exact Sciences, Gilead; Financial Interests, Institutional, Advisory Board: MSD, Exact Sciences, Novartis, Amgen; Financial Interests, Institutional, Sponsor/Funding: BMS, MSD, Astellas, Ipsen, EUSA, Lilly, Roche. J.W. King: Financial Interests, Institutional, Invited Speaker: Exact Science, Pfizer, Roche, Novartis, Lilly, Eisai, Prosigna, AstraZeneca, MSD, Gilead, Seagen. All other authors have declared no conflicts of interest.