Trastuzumab emtansine (T-DM1) in patients with HER2-positive metastatic breast cancer and brain metastases: exploratory final analysis of cohort 1 from KAMILLA, a single-arm phase IIIb clinical trial
Mené sur 2 002 patientes atteintes atteintes d'un cancer du sein HER2+ de stade métastatique et présentant des métastatases cérébrales, cet essai de phase IIIb évalue l'efficacité, du point de vue du taux de réponse globale, de la survie sans progression et de la survie globale, et la toxicité du trastuzumab emtansine
Résumé en anglais
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 (MBC) 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 (BOR; complete response + partial response) and clinical benefit rate (CBR; complete response + partial response + stable disease lasting ≥6 months) by RECIST v1.1 criteria, progression-free survival (PFS), overall survival (OS), and safety.
Results : Of 2002 treated patients, 398 had baseline BM. In 126 patients with measurable BM, the BOR and CBR were 21.4% (95% 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 PFS and OS were 5.5 (95% CI 5.3–5.6) months and 18.9 (95% CI 17.1–21.3) months, respectively. Adverse event (AE) profile was broadly similar in patients with and without baseline BM, although nervous system AEs 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 MBC 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.
