Abstract
Background: KAMILLA is a single-arm safety study of trastuzumab emtansine (T-DM1) in patients with human epidermal growth factor receptor 2 (HER2)-positive advanced breast cancer (BC;NCT01702571). We report the final analysis of cohort 2 (Asia) within the context of published cohort 1 (Global) findings. Methods: Patients had HER2-positive, locally advanced, or metastatic BC progressing after chemotherapy and anti-HER2 therapy or <= 6 months after adjuvant therapy. The primary objective was to further evaluate T-DM1 (3.6 mg/kg, administered intravenously every 3 weeks) safety/tolerability, including the following adverse events of primary interest (AEPIs): grade >= 3 AEPIs (hepatic events, allergic reactions, thrombocytopenia, hemorrhage events), all grade >= 3 treatment-related AEs, and all-grade pneumonitis. Results: KAMILLA enrolled 2185 patients (cohort 1, n = 2003;cohort 2, n = 182) as of 31 July 2019. Of these, 2002 and 181 per cohort were treated and included in the safety population. Approximately 70% of patients had two or more previous treatment lines in the metastatic setting. Median T-DM1 exposure was 5.6 and 5.0 months per cohort;median follow-up was 20.6 and 15.1 months. The overall AEPI rate was higher in cohort 2 (93/181;51.4%) versus cohort 1 (462/2002;23.1%), mostly driven by a higher grade >= 3 thrombocytopenia rate in cohort 2. In cohort 2, grade >= 3 thrombocytopenia was not associated with grade >= 3 hemorrhagic events and most (128/138) fully resolved. Grade >= 3 treatment-related AEPI rates were 18.4% (cohort 1) and 48.6% (cohort 2), the latter mainly due to thrombocytopenia. Any-grade pneumonitis rates were 1.0% and 2.2%. No new safety signals were identified. Median (95% confidence interval) progression-free survival was 6.8 months (5.8-7.6 months) and 5.7 months (5.5-7.0 months) in cohorts 1 and 2, respectively;median overall survival was 27.2 months (25.5-28.7 months) and 29.5 months (21.1 months to non-estimable). In both cohorts, median progression-free survival and overall survival decreased with increasing prior therapy lines. Conclusions: Cohort 2 results aligned with previous findings in Asian patients, supporting the manageable safety profile and use of T-DM1 in advanced BC.
Dokumententyp: | Zeitschriftenartikel |
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Fakultät: | Medizin |
Themengebiete: | 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit |
URN: | urn:nbn:de:bvb:19-epub-106470-4 |
Sprache: | Englisch |
Dokumenten ID: | 106470 |
Datum der Veröffentlichung auf Open Access LMU: | 11. Sep. 2023, 13:39 |
Letzte Änderungen: | 20. Sep. 2023, 13:37 |
DFG: | Gefördert durch die Deutsche Forschungsgemeinschaft (DFG) - 491502892 |