Safety of trastuzumab emtansine (T-DM1) in HER2-positive advanced breast cancer (BC) patients (pts): Primary results from KAMILLA study cohort 1.

Abstract

1033 Background: KAMILLA is a single-arm, open-label, phase 3b safety study of T-DM1 in pts with HER2-positive advanced BC from 278 sites in 40 countries. We report the primary analysis of the first study cohort (N = 2003). Methods: Pts with HER2-positive, locally advanced or metastatic BC (locally confirmed) with progression after prior treatment with chemotherapy and a HER2-directed agent for metastatic BC or within 6 mo of completing adjuvant therapy were enrolled. Pts received T-DM1 3.6 mg/kg every 3 wks until unacceptable toxicity, withdrawal, or disease progression. The primary outcome was safety. Results: A total of 2002 pts were treated (median age 55 yrs, range, 26–88). Most pts had a baseline ECOG score of 0 (n = 1110, 55.4%) or 1 (n = 775, 38.7%), and 1232 (61.5%) had ER and/or PR positive tumors. Median time since initial BC diagnosis was 5 yrs (range, 0–53). Most pts had received ≥2 prior lines of therapy (0–1 prior lines: 29.7%; ≥2: 66.0%); 1855 (92.8%) received prior targeted therapy in the locally advanced/metastatic setting. Median T-DM1 exposure was 5.6 mo (range, 0–46). Adverse events (AEs) were reported in 93.0% (n = 1862). Serious AEs occurred in 21.3% (n = 427), most commonly vomiting (17, 0.8%), pneumonia (16, 0.8%), anemia (13, 0.6%), and pyrexia (13, 0.6%). Grade ≥3 AEs occurred in 40.8% (n = 816), most commonly anemia (60, 3.0%), thrombocytopenia (55, 2.7%), and fatigue (50, 2.5%). Additional AEs of grade ≥3 (multiple individual items grouped) were thrombocytopenia/platelet count decrease (74, 3.7%), hepatic disorders (139, 6.9%), and hemorrhage (46, 2.3%). Grade 5 AEs occurred in 2.2% (n = 45). Treatment discontinuation was most often due to disease progression (1495, 78.1%). Median progression-free survival was 8.3 (95% CI: 8.0–9.7), 6.5 (5.6–8.0), 5.9 (5.6–8.1), 5.6 (5.0–5.9), and 5.6 (5.4–6.6) mo in pts with 0–1, 2, 3, 4, and 5+ prior lines of therapy. Median overall survival was 27.2 mo (95% CI: 25.5–28.7). Conclusions: KAMILLA isthe largest (to date) cohort of T-DM1 treated pts and these data are consistent with safety and efficacy seen in prior randomized studies, thereby supporting T-DM1 as therapy for previously treated HER2-positive advanced BC pts. Clinical trial information: NCT01702571.