Filippo Montemurro1, Paul Ellis2, Antonio Anton3, Rachel Wuerstlein4, Suzette Delaloge5, Jacques Bonneterre6, Nathalie Quenel-Tueux7, Sabine C Linn8, Natsumi Irahara9, Margarita Donica10, Nicolas Lindegger11, Carlos H Barrios12. 1. Investigative Clinical Oncology (INCO), Candiolo Cancer Institute, FPO-IRCCS, Provincial Road 142, 10060, Candiolo, Torino, Italy. Electronic address: filippo.montemurro@ircc.it. 2. Guy's Hospital and Sarah Cannon Research Institute, Great Maze Pond, London, SE1 9RT, United Kingdom. Electronic address: paul.ellis@gstt.nhs.uk. 3. University Hospital Miguel Servet, Aragón Health Research Institute (IIS Aragón), Avda Isabel la Católica 1-3, 50009, Zaragoza, Spain. Electronic address: aantont@gmail.com. 4. Breast Center, University Hospital Munich, Department of Gynecology and Obstetrics Comprehensive Cancer Center, Ludwig Maximilian University, Marchioninistraße 15, 81377, Munich, Germany. Electronic address: Rachel.wuerstlein@med.uni-muenchen.de. 5. Institut Gustave Roussy, 114 Rue Edouard Vaillant, 94800, Villejuif, France. Electronic address: duzette.delaloge@gustaveroussy.fr. 6. Centre Oscar-Lambret, Université Lille Nord de France, 3 Rue Frédéric Combemale, 59000, Lille, France. Electronic address: j-bonneterre@o-lambret.fr. 7. Institut Bergonié Comprehensive Cancer Center, 229 Cours de l'Argonne, 33000, Bordeaux, France. Electronic address: N.Quenel-Tueux@bordeaux.unicancer.fr. 8. The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX, Amsterdam, the Netherlands. Electronic address: s.linn@nki.nl. 9. F. Hoffmann-La Roche Ltd., Konzern-Hauptsitz, Grenzacherstrasse 124, CH-4070, Basel, Switzerland. Electronic address: natsumi.irahara@roche.com. 10. F. Hoffmann-La Roche Ltd., Konzern-Hauptsitz, Grenzacherstrasse 124, CH-4070, Basel, Switzerland. Electronic address: margarita.donica@roche.com. 11. F. Hoffmann-La Roche Ltd., Konzern-Hauptsitz, Grenzacherstrasse 124, CH-4070, Basel, Switzerland. Electronic address: nicolas.lindegger@roche.com. 12. Hospital São Lucas, PUCRS, Av. Ipiranga, 6690 - Jardim Botânico, Porto Alegre, RS 90619-900, Brazil. Electronic address: barrios@tummi.org.
Abstract
BACKGROUND: 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). METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
BACKGROUND: Many patients with metastatic humanepidermal 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). METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
Authors: Michelle D Hackshaw; Heather E Danysh; Jasmeet Singh; Mary E Ritchey; Amy Ladner; Corina Taitt; D Ross Camidge; Hiroji Iwata; Charles A Powell Journal: Breast Cancer Res Treat Date: 2020-06-26 Impact factor: 4.872