ABSTRACT
BACKGROUND: Endocrine therapy is recommended for the treatment of postmenopausal women with hormone receptor-positive (HR+) advanced breast cancer (ABC). METHODS: ACT-FASTER was a German prospective non-interventional cohort study in postmenopausal women with HR+ ABC receiving fulvestrant 500 mg as first line (1 L), second line (2 L) or third line (3 L), or exemestane (any line) in the real-world palliative setting. Primary study objectives included the effectiveness of fulvestrant according to line of palliative treatment measured by time to progression (TTP), and real-life data on the epidemiology and management of these patients. RESULTS: Of 498 evaluable patients (mean age 67.5 years), 99% were estrogen receptor-positive. On study, 86.7% of patients received fulvestrant 500 mg and 13.3% exemestane. Median TTP was 9.7 months in patients receiving fulvestrant 1 L; 6.8 months for 2 L; and 6.7 months for 3 L. The comparison between fulvestrant 1 L palliative treatment and 2 L or 3 L showed that early initiation of treatment prolonged TTP (hazard ratio 1.26; 95% confidence interval 1.08-1.48). Treatments were well tolerated. CONCLUSION: Fulvestrant 500 mg was administered successfully to patients under daily practice conditions, and both medications were well tolerated. TTP was longest in patients treated with fulvestrant 500 mg 1 L compared with 2 L and 3 L in the palliative care setting.
ABSTRACT
Human B cells detect CpG motifs within microbial DNA via TLR9. Synthetic CpG oligodeoxynucleotides are currently being tested in clinical trials for the therapy of different types of B cell non-Hodgkin's lymphoma. However, there is only limited information on the CpG oligodeoxynucleotide sensitivity of primary malignant B cells of different non-Hodgkin's lymphoma entities. Here we found that most B-cell malignancies except plasmacytoma respond to CpG oligodeoxynucleotides by up-regulating expression of costimulatory and antigen-presenting molecules, by increasing expression of CD20, and by proliferation. In an in vitro analysis of 41 individual patient-derived primary tumor samples, B-cell chronic lymphocytic leukemia (B-CLL) and marginal zone lymphoma showed the strongest activation upon stimulation with CpG oligodeoxynucleotides. Small lymphocytic lymphoma, follicular lymphoma, mantle cell lymphoma, and large cell lymphoma showed an intermediate response. Consistent with CpG oligodeoxynucleotides sensitivity, TLR9 mRNA was present in B-CLL but absent in plasmacytoma. Although CpG oligodeoxynucleotides induced proliferation in all CpG oligodeoxynucleotide-sensitive types of B-cell malignancies, proliferation was weaker than in normal B cells and at least for B-CLL was followed by increased apoptosis. In conclusion, B-cell malignancies show significant differences in their responsiveness to CpG oligodeoxynucleotides. Focusing clinical studies on patients with highly CpG oligodeoxynucleotide-sensitive B-cell malignancies may improve the clinical outcome of such trials.
