Body: Background: Over one-third of patients (pts) with HER2-positive (+) advanced breast cancer (BC) develop brain metastases (BM), which often leads to short survival. Afatinib (A), an irreversible ErbB family blocker, demonstrated activity in pts with heavily pretreated, HER2+ metastatic BC (MBC) progressing after trastuzumab (T) therapy, with partial responses (PR) in 10% and clinical benefit in 46% of pts (Lin 2012a). We evaluated the activity of A alone or in combination with vinorelbine (V), versus investigator’s choice of therapy for MBC (IC), in pts with HER2+ BC with BM after prior T and/or lapatinib (L) therapy. Methods: Eligible pts had at least one measurable and progressive lesion in the central nervous system (CNS; ³10 mm on magnetic resonance imaging) after prior systemic and/or radiation therapy. Pts were randomized to receive A (40 mg/day oral), AV (40 mg/day oral + 25 mg/m2/week i.v.) or IC in 3-week cycles. Stratification factors were: ECOG performance status (PS, 0–1 vs 2), number of BM (£3 vs >3) and prior exposure to L (yes/no). The primary endpoint was pt benefit at 12 weeks (i.e. absence of CNS and extra-CNS disease progression per RECIST 1.1, and no tumor-related worsening of neurological signs/symptoms or increase in steroid dosage). Secondary endpoints included progression-free survival (PFS), overall survival (OS), objective response rate (ORR) in CNS/extra-CNS lesions, and safety. Results: 121 pts were randomized (2 were not treated): median age, 53 years; ECOG PS 0–1, 83%; >3 BM, 59%; prior L therapy, 78.5%. The IC treatment consisted of: T+ chemotherapy (CT) (22 pts); T+L+CT (3 pts); L+CT (10 pts); L alone (1 pt); or CT alone (6 pts). In the treated set (n=119), the most frequent treatment-related adverse events (AEs) in the A and AV arms were diarrhea (90% and 84%) and rash (38% and 54%); neutropenia (51%) was also common in the AV arm. Diarrhea (33%), neutropenia (21%) and asthenia (21%) were the most frequent related AEs in the IC arm. Grade (G) 3/4 treatment-related AEs were observed in 50%/3% (A), 57%/24% (AV; G4 AEs were mainly neutropenias) and 14%/7% (IC) of pts; there were no treatment-related G5 events. Conclusions: Approximately one third of pts with HER2+ MBC benefited from the assigned treatments and two thirds had CNS lesions controlled per RECIST in each group. Objective response in CNS was infrequent (0 to 14%) with all treatments. Overall, AEs were manageable in this heavily pretreated pt population.
|Data di pubblicazione:||2014|
|Titolo:||Tumor infiltrating lymphocytes and correlation with pCR in ther CHERLOB study|
|Nome del convegno:||San Antonio Breast Cancer Symposium|
|Data del convegno:||9-13 Dicembre 2014|
|Luogo del convegno:||San Antonio|
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