"In 2015, the Lancet Commission on Global Surgery (LCoGS) published the landmark report titled "Global Surgery 2030: evidence and solutions for achieving health, welfare, and economic development," describing the large, pre-existing burden of surgical diseases in low- and middle-income countries (LMICs) and future directions for increasing universal access to safe surgery by the year 2030. The Commission highlighted that about 5 billion people lack access to safe and affordable surgical and anesthesia care and 143 million additional procedures were needed every year to prevent further morbidity and mortality from treatable surgical conditions as well as a $12.3 trillion loss in economic productivity by the year 2030. This was especially true in the poorest countries, which account for over one-third of the population but only 3.5% of all surgeries that occur worldwide. It emphasized the need to significantly improve the capacity for Bellwether procedures – laparotomy, caesarean section, open fracture care – which are considered a minimum level of care that first-level hospitals should be able to provide in order to capture the most basic emergency surgical care. In terms of the financial impact on the patients, the lack of adequate surgical and anesthesia care has resulted in 33 million individuals every year facing catastrophic health expenditure – the out-of-pocket healthcare cost exceeding 40% of a given households income.In alignment with the LCoGS call for action, the World Health Assembly adopted the resolution WHA68.15 in 2015 that stated, "Strengthening emergency and essential surgical care and anesthesia as a component of universal health coverage."
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.