F Montemurro1, S Delaloge2, C H Barrios3, R Wuerstlein4, A Anton5, E Brain6, T Hatschek7, C M Kelly8, C Peña-Murillo9, M Yilmaz10, M Donica11, P Ellis12. 1. Multidisciplinary Oncology Outpatient Clinic, Candiolo Cancer Institute, FPO-IRCCS, Candiolo, Italy. Electronic address: filippo.montemurro@ircc.it. 2. Breast Cancer Group, Institut Gustave Roussy, Villejuif, France. 3. Oncology Research Center, Hospital São Lucas, PUCRS, Porto Alegre, Brazil. 4. Breast Center, Department of Obstetrics and Gynecology, CCC Muenchen LMU, University of Munich LMU, Munich, Germany. 5. Department of Medical Oncology, Hospital Universitario Miguel Servet, Zaragoza, Spain. 6. Department of Medical Oncology, Hopital René Huguenin/Institut Curie, St Cloud, France. 7. Breast Unit, Department of Oncology, Karolinska University Hospital, Stockholm, Sweden. 8. Department of Oncology, Mater Misericordiae University Hospital, Dublin, Ireland. 9. Global Product Development Medical Affairs, F. Hoffmann-La Roche Ltd., Basel, Switzerland. 10. Personalized Healthcare, F. Hoffmann-La Roche Ltd., Basel, Switzerland. 11. Pharma Development and Medical Affairs, F. Hoffmann-La Roche Ltd., Basel, Switzerland. 12. Department of Medical Oncology, Guy's Hospital, London, UK; Sarah Cannon Research Institute, London, UK.
Abstract
BACKGROUND: Patients with brain metastases (BM) from human epidermal growth factor receptor 2 (HER2)-positive breast cancer represent a difficult-to-treat population. Trastuzumab emtansine (T-DM1) has shown potential activity in this subset of patients in small clinical series. PATIENTS AND METHODS: KAMILLA is an ongoing, phase IIIb study of T-DM1 in patients with HER2-positive locally advanced/metastatic breast cancer with prior HER2-targeted therapy and chemotherapy. Patients received T-DM1 3.6 mg/kg every 3 weeks (intravenously) until unacceptable toxicity, withdrawal of consent, or disease progression. Tumor response and clinical outcomes in patients with baseline BM were evaluated in this post hoc, exploratory analysis. The main outcome measures were best overall response rate (complete response + partial response) and clinical benefit rate (complete response + partial response + stable disease lasting ≥6 months) by RECIST v1.1 criteria, progression-free survival, overall survival, and safety. RESULTS: Of 2002 treated patients, 398 had baseline BM. In 126 patients with measurable BM, the best overall response rate and clinical benefit rate were 21.4% [95% confidence interval (CI) 14.6-29.6] and 42.9% (95% CI 34.1-52.0), respectively. A reduction in the sum of the major diameters of BM ≥30% occurred in 42.9% (95% CI 34.1-52.0), including 49.3% (95% CI 36.9-61.8) of 67 patients without prior radiotherapy to BM. In the 398 patients with baseline BM, median progression-free survival and overall survival were 5.5 (95% CI 5.3-5.6) months and 18.9 (95% CI 17.1-21.3) months, respectively. The adverse event profile was broadly similar in patients with and without baseline BM, although nervous system adverse events were more common in patients with [208 (52.3%)] versus without [701 (43.7%)] baseline BM. CONCLUSION: This exploratory analysis of patients with HER2-positive metastatic breast cancer and BM enrolled in a prospective clinical trial shows that T-DM1 is active and well-tolerated in this population. T-DM1 should be explored further in this setting. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01702571.
BACKGROUND:Patients with brain metastases (BM) from humanepidermal growth factor receptor 2 (HER2)-positive breast cancer represent a difficult-to-treat population. Trastuzumab emtansine (T-DM1) has shown potential activity in this subset of patients in small clinical series. PATIENTS AND METHODS: KAMILLA is an ongoing, phase IIIb study of T-DM1 in patients with HER2-positive locally advanced/metastatic breast cancer with prior HER2-targeted therapy and chemotherapy. Patients received T-DM1 3.6 mg/kg every 3 weeks (intravenously) until unacceptable toxicity, withdrawal of consent, or disease progression. Tumor response and clinical outcomes in patients with baseline BM were evaluated in this post hoc, exploratory analysis. The main outcome measures were best overall response rate (complete response + partial response) and clinical benefit rate (complete response + partial response + stable disease lasting ≥6 months) by RECIST v1.1 criteria, progression-free survival, overall survival, and safety. RESULTS: Of 2002 treated patients, 398 had baseline BM. In 126 patients with measurable BM, the best overall response rate and clinical benefit rate were 21.4% [95% confidence interval (CI) 14.6-29.6] and 42.9% (95% CI 34.1-52.0), respectively. A reduction in the sum of the major diameters of BM ≥30% occurred in 42.9% (95% CI 34.1-52.0), including 49.3% (95% CI 36.9-61.8) of 67 patients without prior radiotherapy to BM. In the 398 patients with baseline BM, median progression-free survival and overall survival were 5.5 (95% CI 5.3-5.6) months and 18.9 (95% CI 17.1-21.3) months, respectively. The adverse event profile was broadly similar in patients with and without baseline BM, although nervous system adverse events were more common in patients with [208 (52.3%)] versus without [701 (43.7%)] baseline BM. CONCLUSION: This exploratory analysis of patients with HER2-positive metastatic breast cancer and BM enrolled in a prospective clinical trial shows that T-DM1 is active and well-tolerated in this population. T-DM1 should be explored further in this setting. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01702571.
Authors: Diana Lüftner; Peter A Fasching; Renate Haidinger; Nadia Harbeck; Christian Jackisch; Volkmar Müller; Eva Schumacher-Wulf; Christoph Thomssen; Michael Untch; Rachel Würstlein Journal: Breast Care (Basel) Date: 2022-01-20 Impact factor: 2.860
Authors: Markus Kuksis; Yizhuo Gao; William Tran; Christianne Hoey; Alex Kiss; Adam S Komorowski; Aman J Dhaliwal; Arjun Sahgal; Sunit Das; Kelvin K Chan; Katarzyna J Jerzak Journal: Neuro Oncol Date: 2021-06-01 Impact factor: 12.300