Unleashing NK- and CD8 T cells by combining monalizumab and trastuzumab for metastatic HER2-positive breast cancer: Results of the MIMOSA trial.

The large majority of patients with HER2-positive metastatic breast cancer (MBC) will eventually develop resistance to anti-HER2 therapy and die of this disease. Despite, relatively high levels of stromal tumor infiltrating lymphocytes (sTILs), PD1-blockade has only shown modest responses. Monalizumab targets the inhibitory immune checkpoint NKG2A, thereby unleashing NK- and CD8 T cells. We hypothesized that monalizumab synergizes with trastuzumab by promoting antibody-dependent cell-mediated cytotoxicity. In the phase II MIMOSA-trial, HER2-positive MBC patients were treated with trastuzumab and 750 mg monalizumab every two weeks. Following a Simon's two-stage design, 11 patients were included in stage I of the trial. Treatment was well tolerated with no dose-limiting toxicities. No objective responses were observed. Therefore, the MIMOSA-trial did not meet its primary endpoint. In summary, despite the strong preclinical rationale, the novel combination of monalizumab and trastuzumab does not induce objective responses in heavily pre-treated HER2-positive MBC patients.

[Diagnosis and therapy of gestational diabetes--comparison of two surveys of established gynecologists in Berlin and Saxonia-Anhalt ]. / Diagnostik und Therapie des Gestationsdiabetes -- Vergleich zweier Umfragen unter niedergelassenen Gynäkologen/Innen in Berlin und Sachsen-Anhalt.

PURPOSE: The diagnosis and treatment of gestational diabetes mellitus is controversial. We undertook a survey of obstetricians/gynaecologists to identify current screening practices and differences between Saxonia-Anhalt and Berlin. METHODS: A questionnaire was sent to 267 practicing obstetricians/gynaecologists in Saxonia-Anhalt and 441 in Berlin. The questionnaires included items on the diagnosis and treatment of gestational diabetes. RESULTS: A response rate of 37 % in Saxonia-Anhalt and 35 % in Berlin was achieved. 90 % of the respondents would welcome the integration of a general screening for gestational diabetes into the standard German prenatal care plan. In spite of this great support only 37 % of the obstetricians/gynaecologists in Saxonia-Anhalt and 36 % in Berlin screened their patients generally. Important risk factors for the screening were rarely or not mentioned. CONCLUSION AND DISCUSSION: The survey confirms disparate policies regarding the screening for and treatment of gestational diabetes. There are differences between Saxonia-Anhalt and Berlin. This can only be changed by appropriate inclusion in the German prenatal care plan.