About 50% of all primary breast cancers show a low-level expression of HER2 (HER2-low), defined as immunohistochemically 1+ or 2+ and lack of HER2 gene amplification measured by in situ ...hybridization. This low HER2 expression is a promising new target for antibody-drug conjugates (ADCs) currently under investigation. Until now, little is known about the frequency and the prognostic value of low HER2-expression in metastatic breast cancer (MBC).
The MBC-Registry of the Austrian Study Group of Medical Tumor Therapy (AGMT) is a multicenter nationwide ongoing registry for MBC patients in Austria. Unadjusted, univariate survival probabilities of progression-free survival (PFS) and overall survival (OS) were calculated by the Kaplan-Meier method and compared by the log-rank test. Multivariable adjusted hazard ratios were estimated by Cox regression models. In this analysis, only patients with known HER2 status and available survival data were included.
As of 11/15/2020, 1,973 patients were included in the AGMT-MBC-Registry. Out of 1,729 evaluable patients, 351 (20.3%) were HER2-positive, 608 (35.2%) were HER2-low and 770 (44.5%) were completely HER2-negative (HER2-0). Low HER2-expression was markedly more frequent in the hormone-receptor(HR)+ subgroup compared to the triple-negative subgroup (40% vs. 23%). In multivariable analysis, low HER2 expression did not significantly influence OS neither in the HR+ (HR 0.89; 95% CI 0.74-1.05; P = 0.171) nor in the triple-negative subgroup (HR 0.92; 95% CI 0.68-1.25; P = 0.585), when compared to completely HER2-negative disease. Similar results were observed when HER2 IHC 2+ patients were compared to IHC 1+ or 0 patients.
Low-HER2 expression did not have any impact on prognosis of metastatic breast cancer in this real-world population.
In this prospective study (NCT01595295), 272 patients treated with azacitidine completed 1456 EuroQol 5-Dimension (EQ-5D) questionnaires. Linear mixed-effect modelling was used to incorporate ...longitudinal data. When compared with a matched reference population, myeloid patients reported more pronounced restrictions in usual activities (+28%,
< 0.0001), anxiety/depression (+21%,
< 0.0001), selfcare (+18%,
< 0.0001) and mobility (+15%,
< 0.0001), as well as lower mean EQ-5D-5L indices (0.81 vs. 0.88,
< 0.0001), and lower self-rated health on the EuroQol Visual Analogue Scale (EQ-VAS) (64 vs. 72%,
< 0.0001). After multivariate-adjustment, (i) the EQ-5D-5L index assessed at azacitidine start the predicted time with clinical benefit (TCB) (9.6 vs. 6.6 months;
= 0.0258; HR = 1.43), time to next treatment (TTNT) (12.8 vs. 9.8 months;
= 0.0332; HR = 1.42) and overall survival (OS) (17.9 vs. 12.9 months;
= 0.0143; HR = 1.52); (ii) Level Sum Score (LSS) predicted azacitidine response (
= 0.0160; OR = 0.451) and the EQ-5D-5L index showed a trend (
= 0.0627; OR = 0.522); (iii) up to 1432 longitudinally assessed EQ-5D-5L response/clinical parameter pairs revealed significant associations of EQ-5D-5L response parameters with haemoglobin level, transfusion dependence and hematologic improvement. Significant increases of the likelihood ratios were observed after addition of LSS, EQ-VAS or EQ-5D-5L-index to the International Prognostic Scoring System (IPSS) or the revised IPSS (R-IPSS), indicating that they provide added value to these scores.
STEPAUT, an Austrian non-interventional study, evaluated the safety and efficacy of everolimus plus exemestane in patients with hormone receptor-positive (HR+), human epidermal growth factor receptor ...2-negative (HER2−) advanced breast cancer (ABC) recurring/progressing on/after nonsteroidal aromatase inhibitors (NSAIs) in routine clinical practice.
Postmenopausal women with HR+, HER2− ABC progressing on/after NSAIs receiving everolimus plus exemestane in accordance with routine practice and the current version of Summary of Product Characteristics were eligible. Planned individual observation period corresponded to the duration of treatment until formal study end.
Overall, 236 patients (median age: 65 years) were enrolled at 17 sites across Austria. The median progression-free survival (mPFS) in the overall population was 9.5 months (95% confidence interval CI: 8.6–10.7 months). The mPFS (95% CI) in patients who received everolimus 10 and 5 mg was 9.9 months (7.3–11.5 months) and 8 months (4.7–10.7 months), respectively. The median time to progression was numerically longer in patients who had a therapy break (11.9 months, 95% CI: 10.0–14.6 months) versus those who did not have any therapy break (10.7 months, 95% CI: 8.9–12.6 months). Patients experienced grade 1 (53.7%), grade 2 (35.9%), grade 3 (9.9%), grade 4 (0.2%) adverse events (AEs). The most common AEs of any grade were stomatitis, mucositis (53.8%), rash, exanthema (29.7%), loss of appetite, nausea (28.4%).
Real-world safety and efficacy data from STEPAUT were consistent with results from BOLERO-2, supporting everolimus plus exemestane as a suitable treatment option for HR+, HER2− ABC recurring/progressing on/after NSAIs.
•STEPAUT, an Austrian non-interventional study, evaluated everolimus plus exemestane.•The median progression-free survival in the overall population was 9.5 months.•Majority of the patients had grade 1 (53.7%) to grade 2 (35.9%) adverse events.•Real-world data from STEPAUT were consistent with results from the BOLERO-2.
Trial registration: BASG, AGES, NIS002843
Azacitidine is the treatment backbone for patients with acute myeloid leukemia, myelodysplastic syndromes and chronic myelomonocytic leukemia who are considered unfit for intensive chemotherapy. ...Detailed reports on adverse events in a real-world setting are lacking.
To analyze the frequency of adverse events in the Austrian Registry of Hypomethylating agents. To compare real-world data with that of published randomized clinical trials.
A total of 1406 patients uniformly treated with a total of 13,780 cycles of azacitidine were analyzed. Hematologic adverse events were the most common adverse events (grade 3-4 anemia 43.4%, grade 3-4 thrombopenia 36.8%, grade 3-4 neutropenia 36.1%). Grade 3-4 anemia was significantly more common in the Registry compared to published trials. Febrile neutropenia occurred in 33.4% of patients and was also more common in the Registry than in published reports. Other commonly reported adverse events included fatigue (33.4%), pain (29.2%), pyrexia (23.5%), and injection site reactions (23.2%). Treatment termination due to an adverse event was rare (5.1%).
The safety profile of azacitidine in clinical trials is reproducible in a real-world setting. With the use of prophylactic and concomitant medications, adverse events can be mitigated and azacitidine can be safely administered to almost all patients with few treatment discontinuations.
The clinical presentation of patients infected with SARS-CoV-2 is remarkably diverse. Likewise, the underlying pathophysiological mechanisms are proving complex. Disturbances in the blood coagulation ...system and cytokine storm, such as seen in hemophagocytic syndrome, are among the most serious ones. We present the case of a female 79-year-old patient with marked thrombocytopenia of 4 (150-450) x10^9/L occurring in the context of a confirmed SARS-CoV-2 infection. Clinically, one episode of epistaxis and petechiae was observed, otherwise no signs of bleeding occurred. Diagnostic workup included microscopic blood smear analysis, bone marrow cytologic evaluation and flow cytometric immunophenotyping. Hematological malignancies, thrombotic microangiopathies and common infections were excluded as cause of the low platelet count. In the bone marrow, cytology, the megakaryocytic lineage presented normocellular. However, several large hemophagocytes with engulfed hematopoietic cells were detected. A further evaluation of markers frequently associated with hemophagocytic syndrome was performed. Ferritin was 2888 (0-150) ng/mL, CRP and GOT were slightly elevated. The white blood count was normal with a marked decrease of lymphocytes to 0.13 (1.10-3.60) × 10^9/L. There was no fever or organomegaly and the patient was in good clinical constitution. Thus, we did not diagnose hemophagocytic syndrome. Due to no other explanation for the clinical and laboratory findings, the patient was diagnosed with immune thrombocytopenia and concomitant bone marrow hemophagocytosis associated to SARS-CoV-2. The first-line treatment consisting of prednisolone and intravenous immunoglobulins failed to induce an increase in the platelet count. As second-line treatment therapy with Eltrombopag, a TPO-agonist, was started and a sustainable response with platelets in the normal range was achieved.
Abstract
Since the broad implementation of ibrutinib therapy, an increasing number of studies have been reported on invasive fungal infections (IFI) associated with ibrutinib administration. We ...conducted a retrospective cohort study in three hospitals in south-east Austria in order to assess the local epidemiology of ibrutinib associated IFIs. A total of 113 patients with underlying hematological malignancy were included in the study. During the study period, a single IFI episode was observed, which corresponds to an IFI incidence of 2.3 cases per 100 person years (95% CI: 0.12–11.47). IFIs during ibrutinib therapy seem to be a rare event in case of absent additional risk factors for IFIs.
Lay Summary
Ibrutinib is an effective drug used to treat a variety of blood cancers, but it might increase risk for life-threatening invasive fungal infections (IFIs). In our study, a low number (1 IFI per 43 patient years) of patients on ibrutinib developed an IFI.
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