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.

Chemotherapy for ovarian cancer in the Netherlands: a population-based study on treatment patterns and outcomes.

Information on treatment patterns for ovarian cancer (OC) is limited. The aim of this study was to describe current patterns of chemotherapy and other systemic treatments for OC in the Netherlands and evaluate survival outcomes following subsequent lines of treatment. Data from the Eindhoven Cancer Registry, including on newly diagnosed cancer patients, were linked to the PHARMO Database Network, including information on in- and out-patient drug use. Patients diagnosed with OC between January 2000 and December 2010 were selected. An algorithm was used to identify separate lines of treatment. Data were studied descriptively. Detailed data on systemic drug use were available for 261 patients (17%) with OC. In first-line treatment, 87% of the patients (227/261) received platinum-based chemotherapy. Of the 161 patients receiving second-line treatment, 101 patients (63%) received platinum-based chemotherapy. In third line, this was 51% (53/103). The median number of treatment lines received by patients was two (interquartile range 1-3), and eight or more lines of chemotherapy were identified for 12 patients. Median survival from diagnosis onwards was 47 months from the end of first-line treatment, median survival was 32 months, and from the end of second-line treatment, it was 14 months. Predominantly beyond second-line treatment, there is much variety in treatment patterns with chemotherapy for OC. Although uncertainty remains regarding the desirability of this observed treatment variation, there seems a need for detailed clinical guidance, assuring that physicians can properly choose the most suitable treatment for each patient.

Principles and applications of nanofluidic transport.

The evolution from microfluidic to nanofluidic systems has been accompanied by the emergence of new fluid phenomena and the potential for new nanofluidic devices. This review provides an introduction to the theory of nanofluidic transport, focusing on the various forces that influence the movement of both solvents and solutes through nanochannels, and reviews the applications of nanofluidic devices in separation science and energy conversion.