Attrition between lines of therapy and real-world outcomes of patients with HER2-positive metastatic breast cancer in Europe: a cohort study leveraging electronic medical records

Purpose: To characterize real-world attrition rates across first-line (1L) to third-line (3L) therapies in patients with HER2-positive (HER2 +) metastatic breast cancer (mBC) receiving routine care in seven hospital systems across Europe (France, Germany, Italy, Spain, and the UK).

Methods: This retrospective, observational, multi-country, cohort study collected electronic medical record data from women aged ≥ 18 years diagnosed with HER2 + mBC from 2017-2021. The primary endpoint was attrition rate (the proportion of patients receiving a line of therapy [LOT] with no further evidence of subsequent LOTs). Key additional endpoints included treatment patterns, real-world time to treatment discontinuation (TTD), and time to next treatment (TTNT).

Results: 29.6% (95% confidence interval [CI] 25.0-34.6) and 34.2% (95% CI 27.5-41.5) of treated patients with HER2 + mBC had no further evidence of treatment beyond 1L and second-line (2L) therapy, respectively. Attrition was primarily owing to death, move to end-of-life palliative care, loss to follow up, and "other" reasons. Treatment patterns were generally aligned with clinical guidelines. Decreases in TTD (12.1 months [95% CI 10.4-14.5] for 1L, 8.9 months [95% CI 7.3-11.9] for 2L, 6.4 months [95% CI 5.2-8.9] for 3L) and TTNT (15.4 months [95% CI 13.6-20.6] for 1L, 13.5 months [95% CI 10.8-19.4] for 2L) were observed with each subsequent LOT.

Conclusion: Results unveil a large proportion of patients who do not benefit from state-of-the-art subsequent LOT, and suggest diminishing effectiveness with each subsequent LOT.