Abstract Ruxolitinib, a JAK1/JAK2 inhibitor, has demonstrated efficacy in achieving hematocrit control, spleen volume reductions, and symptom improvement in patients with polycythaemia vera (PV) resistant to or intolerant of hydroxyurea in clinical trials. PaVe is a prospective, noninterventional study of patients with PV who received ruxolitinib in a real-world setting in Germany. Observational parameters included effectiveness, safety, patient satisfaction and quality of life. Patients with and without prior treatment with ruxolitinib were included in this study. Additionally, patients were stratified by no/high risk. The study was primarily analyzed using descriptive methods. Four hundred and thirty-three patients with PV were included in this study, of which 62% were pretreated with a JAK-inhibitor and 38% were not. Mean decreases from Baseline in hematocrit levels/leukocyte counts at the last assessment were more pronounced in naïve patients (-6.2% versus − 1.6%/-4.5 × 103/µl versus − 1.4 × 103/µl) and high-risk patients (-6.3% versus − 5.3%/-4.8 × 103/µl versus − 2.6 × 103/µl). Mean decreases from Baseline in thrombocyte counts at the last assessment were more pronounced in naïve patients (-80.5 × 103/µl versus − 42.6 × 103/µl) and no-risk patients (-108.0 × 103/µl versus − 77.1 × 103/µl). There was almost no difference in the total number of thromboembolic events in JAK inhibitor naïve versus JAK inhibitor pretreated patients (3.1%, n = 5 versus 3.8%, n = 10). No new safety concerns were observed with ruxolitinib. Findings from this study in a real-world setting show that ruxolitinib is an effective and safe second-line treatment in PV patients.
Cyclin-dependent kinase 4 and 6 inhibitors (CDK4/6i) combined with endocrine therapy are the preferred choice for first-line treatment of patients with HR+/HER2- locally advanced/metastatic breast cancer (aBC). The CDK4/6i ribociclib in combination with an aromatase inhibitor (AI) or fulvestrant (FUL) has demonstrated significant progression-free survival (PFS) and overall survival (OS) benefits for pre- and postmenopausal aBC patients who were enrolled in the three pivotal MONALEESA trials. Following the initial approval of ribociclib in 2017, the non-interventional RIBANNA study was initiated to evaluate the effectiveness and safety of ribociclib plus AI/FUL therapy among patients with aBC in a real-world setting. Two additional treatment cohorts (endocrine monotherapy [ET] and chemotherapy [CT]) were included to extend the knowledge about current aBC treatments. A total of 2567 patients were enrolled in 279 study centers, of whom 1852 were treated with ribociclib+AI/FUL, 183 were treated with ET, and 139 were treated with CT, who were available for effectiveness analyses. Median PFS (mPFS) and median OS (mOS) on first-line treatment with ribociclib+AI/FUL were 35.0 and 76.0 months, respectively. Adjustment for differences in demographic and baseline characteristics resulted in a longer mPFS on ribociclib+AI/FUL (34.7 months) compared to ET (26.4 months) or CT (19.2 months). Adverse events (AEs) on ribociclib were consistent with those seen in the pivotal trials, and no new safety signals were observed. The RIBANNA study confirmed the PFS and OS benefit seen in the MONALEESA trials. Together with the safety data, this large real-world dataset supports the favorable risk/benefit profile of ribociclib in large scale patient populations.
BACKGROUND:Leptomeningeal metastases (LM) in patients with breast cancer (BC) are associated with a dismal prognosis. We explored clinical characteristics and prognostic factors in patients with BC and LM in the German Brain Metastases in Breast Cancer Registry. METHODS:All patients with histologically confirmed BC and diagnosis of LM (defined as the presence of tumor cells in the cerebrospinal fluid, or presence of typical clinical symptoms in combination with typical magnetic resonance imaging findings) were included. RESULTS:A total of 3857 patients were included in the analysis (n = 859 (22.3 %) with LM). Among patients with LM a median progression-free survival was 4.2 months (95 % CI 3.6-4.8), and median overall survival was 5.7 months (95 % CI 4.9-6.7). In the multivariate analysis older age ( ≥ 60 vs. <60 years, Hazard ratio (HR): 1.65, 95 %CI: 1.25-2.18), worse performance status (ECOG 2-4 vs. 0-1 HR: 2.15, 95 %CI: 1.63-2.82), hormone receptor positive/HER2-negative (HR+/HER2-) or triple-negative subtype (HR: 1.54 95CI%: 1.07-2.23 and HR: 1.87, 95 %CI: 1.25-2.81), and higher number of BM (2-3 vs. 1, HR: 1.49, 95 %CI: 1.05-2.11 4) were significantly associated with a higher risk of death. Stereotactic radiotherapy (HR 0.49 95 %CI 0.30-0.79) and whole brain irradiation (HR: 0.58, 95 %CI: 0.42-0.80), endocrine therapy in patients with HR + BC (HR: 0.31, 95 %CI: 0.21-0.45) as well as HER2-targeted therapy for patients with HER2+ BC (HR 0.41, 95 %CI: 0.25-0.68) were associated with a significantly longer survival. CONCLUSIONS:Clinicopathological factors associated with survival can help clinicians identify patients who are candidates for treatment (de)escalation in clinical trials.
BACKGROUND:Progression-free survival (PFS) for patients with metastatic hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) breast cancer significantly improved with cyclin-dependent kinase 4/6 inhibitors as part of first-line treatment. No data is available for these patients on how the risk of progression evolves. Therefore, we analyzed conditional PFS (cPFS), which reflects patient prognosis after initial management, that is, the probability of remaining free from progression in those who have already survived without progression for a given period. PATIENTS AND METHODS:We analyzed PFS and cPFS for patients free from progression after 12, 24, and 36 months (reference time points) treated with ribociclib and endocrine therapy (ET) as first-line treatment for advanced HR+, HER2- breast cancer (aBC) within the RIBANNA noninterventional study (NCT06311383). Relevant subgroups with established prognostic factors were additionally examined. RESULTS:Compared with the median PFS of 35 months (95% confidence interval 32.3-38.4 months) in the overall population, the median cPFS was higher for all reference points: cPFS of 40.5 months (95% confidence interval 35.0-45.5 months) for patients who were progression-free 12 months, cPFS of 53.6 months (95% confidence interval 42.7-not reached months) for 24 months reference point, whereas for the 36 months reference point, the median cPFS was not reached. After patients had reached 2-year disease control, the initial presence of liver metastases or grade 3 disease no longer qualified as poor prognostic factors; internal organ metastases (central nervous system, liver, and lungs) showed a diminishing prognostic impact over time. A short treatment-free interval remained a relevant prognostic factor. CONCLUSION:For the first time, increasing cPFS was demonstrated in patients treated with ribociclib and ET. Such information is highly relevant and reassuring for patients with HR+, HER2- aBC, and could be used to aid patient counseling and treatment decision-making, including possible de-escalation strategies. It is also a starting point for identifying dynamic prognostic factors related to long-term survival.
Background Patients with indolent B-cell non-Hodgkin lymphomas (B-NHLs) have an increased risk of infections which is caused by pathomechanisms of the diseases itself but also as a result of anti-tumor therapy. Especially the effects of anti-CD20 antibodies are well understood as these lead to decreased antibody production. Most studies regarding immunodeficiency in B-NHLs were conducted with multiple myeloma and chronic lymphocytic leukemia patients. As these studies not always represent the general population we collected and analyzed real world data from patients with indolent lymphomas and a control group (CG). Results Patients with B-NHLs undergoing therapy or who were regularly monitored in a watch and wait approach had, over the time of one year, an increased rate of infections compared to the CG of 145 healthy volunteers (mean: 11.66 vs. 7.13 infections per 1000 days). Consistent with this finding B-NHL patients received more antibiotic treatment (mean: 11.17 vs. 6.27 days) and were more often hospitalized than persons from the CG (mean: 5.19 vs. 0.99 days per 1000 days). Lymphoma patients without immunodeficiency had a lower infection rate than patients with non-symptomatic and symptomatic immunodeficiency (mean: 10.91 vs. 12.07 and 12.36 per 1000 days). The number of infections differed statistically significant for the subgroups and CG (7.13 per 1000 days). Patients with symptomatic immunodeficiency were mostly treated with regular immunoglobulin substitutions and infection rates were comparable to those of patients with asymptomatic immunodeficiency. Conclusions Our data suggest the use of an approach with regular immune monitoring including the measurement of immunoglobulin levels and regular appointments for clinical assessment of all indolent lymphoma patients in order to identify patients with increased risk of infections. It also raises the question if patients with immunodeficiency should be treated more often with regular immunoglobulin substitution, but so far more studies are necessary to answer this question.
