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

• Published in: European journal of cancer (1990) 2019-03, Vol.109, p.92-102
• Main Authors: Montemurro, Filippo, Ellis, Paul, Anton, Antonio, Wuerstlein, Rachel, Delaloge, Suzette, Bonneterre, Jacques, Quenel-Tueux, Nathalie, Linn, Sabine C., Irahara, Natsumi, Donica, Margarita, Lindegger, Nicolas, Barrios, Carlos H.
• Format: Article
• Language: English
• Subjects: Ado-trastuzumab emtansine; Ado-Trastuzumab Emtansine - therapeutic use; Adult; Aged; Aged, 80 and over; Anemia; Antineoplastic Agents, Immunological - therapeutic use; Brain Neoplasms - drug therapy; Brain Neoplasms - secondary; Breast cancer; Breast Neoplasms - drug therapy; Breast Neoplasms - pathology; Cancer; Central nervous system; Chemotherapy; Clinical trial, Phase III; Cohort Studies; Confidence intervals; Drug-related side effects and adverse reactions; Epidermal growth factor; ErbB-2 protein; Female; Follow-Up Studies; Growth factors; Humans; Immunotherapy; Lymphatic Metastasis; Malignant neoplasm of breast; Medical treatment; Metastases; Metastasis; Middle Aged; Monoclonal antibodies; Patients; Prognosis; Receptor, epidermal growth factor; Receptor, ErbB-2; Safety; Survival; Survival Rate; Targeted cancer therapy; Thrombocytopenia; Toxic diseases; Toxicity; Trastuzumab
• ISSN: 0959-8049; 1879-0852
• DOI: 10.1016/j.ejca.2018.12.022

Many patients with metastatic human epidermal growth factor receptor 2 (HER2)-positive breast cancer (BC) are candidates for trastuzumab emtansine (T-DM1) treatment sometime in their disease history. KAMILLA evaluated safety of T-DM1 in patients with previously treated HER2-positive locally advanced or metastatic BC (advanced BC). KAMILLA (NCT01702571) is a single-arm, open-label, international, phase IIIb safety study of patients with HER2-positive advanced BC with progression after prior treatment with chemotherapy and a HER2-directed agent for MBC or within 6 months of completing adjuvant therapy. Patients received T-DM1 (3.6 mg/kg every 3 weeks) until unacceptable toxicity, withdrawal or disease progression. Among 2002 treated patients, median age was 55 years (range, 26–88; 373 [18.6%] aged ≥65 years), 1321 (66.0%) received ≥2 prior metastatic treatment lines and 398 (19.9%) had baseline central nervous system metastases. Adverse events (AEs) and serious AEs occurred in 1862 (93.0%) and 427 (21.3%) patients, respectively. Grade ≥3 AEs occurred in 751 (37.5%) patients; the three most common (individual Medical Dictionary for Regulatory Activity terms) were anaemia (3.0%), thrombocytopaenia (2.7%) and fatigue (2.5%). Median progression-free survival (PFS) was 6.9 months (95% confidence interval [CI], 6.0–7.6). Median overall survival (OS) was 27.2 months (95% CI, 25.5–28.7). With increasing lines of prior advanced therapy (0–1 versus 4+), median PFS and OS decreased numerically from 8.3 to 5.6 months and from 31.3 to 22.5 months, respectively. KAMILLA is the largest cohort of T-DM1–treated patients studied to date. Results are consistent with prior randomised studies, thereby supporting T-DM1 as safe, tolerable and efficacious treatment for patients with previously treated HER2-positive advanced BC. •KAMILLA is the largest cohort of T-DM1–treated patients studied to date (N = 2002).•Results support continued T-DM1 use in HER2-positive advanced breast cancer.•KAMILLA patients represent a broader population than previous registration studies.•T-DM1 was safe, tolerable and efficacious in HER2-positive advanced breast cancer.•Median progression-free and overall survival were 6.9 and 27.2 months, respectively.