Final results of the global and Asia cohorts of KAMILLA, a phase IIIB safety trial of trastuzumab emtansine in patients with HER2-positive advanced breast cancer

• Published in: ESMO open Vol. 7; no. 5; p. 100561
• Main Authors: Wuerstlein, R., Ellis, P., Montemurro, F., Antón Torres, A., Delaloge, S., Zhang, Q., Wang, X., Wang, S., Shao, Z., Li, H., Rachman, A., Vongsaisuwon, M., Liu, H., Fear, S., Peña-Murillo, C., Barrios, C.
• Format: Journal Article
• Language: English
• Published: Elsevier Ltd 01-10-2022; Elsevier
• Subjects: Asia; HER2-positive metastatic breast cancer; KAMILLA; Original Research; safety; trastuzumab emtansine (TDM-1); KAMILLA; Asia; HER2-positive metastatic breast cancer; safety; trastuzumab emtansine (TDM-1)
• ISSN: 2059-7029; 2059-7029
• DOI: 10.1016/j.esmoop.2022.100561

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.
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.
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.
Cohort 2 results aligned with previous findings in Asian patients, supporting the manageable safety profile and use of T-DM1 in advanced BC.
•KAMILLA safety results for cohorts 1 (global; n = 2002) and 2 (Asia; n = 181) aligned with results from prior T-DM1 mBC trials.•The overall rate of adverse events of primary interest (AEPIs) was higher in cohort 2 (51.4%) versus cohort 1 (23.1%).•The higher AEPI rate was mostly due to a higher grade ≥3 thrombocytopenia event rate in cohort 2, most of which resolved.•Median PFS and OS were similar for both cohorts, and decreased with increasing prior therapy lines.•The manageable safety profile and efficacy of T-DM1 further support its favorable benefit/risk balance.