Interstitial lung disease and pneumonitis, including cases resulting in death, have been reported with trastuzumab deruxtecan. History
The FDA approved trastuzumab deruxtecan based on the results of one clinical trial enrolling 184 female participants with HER2-positive, unresectable and/or metastatic breast cancer who had received two or more prior anti-HER2 therapies in the metastatic setting. These participants were heavily pretreated in the metastatic setting, receiving between two and 17 therapies prior to receiving trastuzumab deruxtecan. Participants in the clinical trial received trastuzumab deruxtecan every three weeks and tumor imaging was obtained every six weeks. The overall response rate was 60.3%, which reflects the percentage of participants who had a certain amount of tumor shrinkage with a median duration of response of 14.8 months.Efficacy was evaluated in a multicenter, open-label, randomized trial (DESTINY-Gastric01, NCT03329690) in participants with HER2-positive locally advanced or metastatic gastric or GEJ adenocarcinoma who had progressed on at least two prior regimens, including trastuzumab, a fluoropyrimidine- and a platinum-containing chemotherapy. A total of 188 participants were randomized (2:1) to receive trastuzumab deruxtecan 6.4 mg/kg intravenously every three weeks or physician’s choice of either irinotecan or paclitaxel monotherapy.Efficacy was based on DESTINY-Breast03 (NCT03529110), a multicenter, open-label, randomized trial that enrolled 524 participants with HER2-positive, unresectable, and/or metastatic breast cancer who received prior trastuzumab and taxane therapy for metastatic disease or developed disease recurrence during or within six months of completing neoadjuvant or adjuvant therapy.
They are also expensive and vulnerable to damage from falling rocks in the warmer months. In addition to industrially manufactured barriers, landscaped barriers, called avalanche dams stop or deflect avalanches with their weight and strength. These barriers are made out of concrete, rocks, or earth. They are usually placed right above the structure, road, or railway that they are trying to protect, although they can also be used to channel avalanches into other barriers. Occasionally, earth mounds are placed in the avalanches path to slow it down. Finally, along transportation corridors, large shelters, called snow sheds, can be built directly in the slide path of an avalanche to protect traffic from avalanches. Early warning systems
Warning systems can detect avalanches which develop slowly, such as ice avalanches caused by icefalls from glaciers. Interferometric radars, high-resolution cameras, or motion sensors can monitor instable areas over a long term, lasting from days to years. Experts interpret the recorded data and are able to recognize upcoming ruptures in order to initiate appropriate measures. Such systems (e.g. the monitoring of the Weissmies glacier in Switzerland) can recognize events several days in advance. Alarm systems
Modern radar technology enables the monitoring of large areas and the localization of avalanches at any weather condition, by day and by night. Complex alarm systems are able to detect avalanches within a short time in order to close (e.g. roads and rails) or evacuate (e.g. construction sites) endangered areas. An example of such a system is installed on the only access road of Zermatt in Switzerland.