Background: Trastuzumab deruxtecan (DS-8201) is certainly an antibody-drug conjugate made up of the anti-HER2 (human epidermal growth factor receptor 2) antibody, a cleavable tetrapeptide-based linker, plus a cytotoxic topoisomerase I inhibitor. The drug may have effectiveness in patients with HER2-positive advanced gastric cancer.
Methods: Inside an open-label, randomized, phase 2 trial, we evaluated trastuzumab deruxtecan when compared with chemotherapy in patients with HER2-positive advanced gastric cancer. Patients with centrally confirmed HER2-positive gastric or gastroesophageal junction adenocarcinoma which in fact had progressed once they were receiving no less than two previous therapies, including trastuzumab, were randomly assigned in the 2:1 ratio to obtain trastuzumab deruxtecan (6.4 mg per kilogram of bodyweight every three days) or physician’s choice of chemotherapy. The primary finish point was the goal response, according to independent central review. Secondary finish points incorporated overall survival, response duration, progression-free survival, confirmed response (response persisting ?Y4 days), and safety.
Results: Of 187 treated patients, 125 received trastuzumab deruxtecan and 62 chemotherapy (55 received irinotecan and 7 paclitaxel). An objective response was reported in 51% from the sufferers inside the trastuzumab deruxtecan group, when compared with 14% of people inside the physician’s choice group (P<0.001). Overall survival was longer with trastuzumab deruxtecan than with chemotherapy (median, 12.5 vs. 8.4 months hazard ratio for death, 0.59 95% confidence interval, 0.39 to 0.88 P = 0.01, which crossed the prespecified O’Brien-Fleming boundary [0.0202 on the basis of number of deaths]). The most common adverse events of grade 3 or higher were a decreased neutrophil count (in 51% of the trastuzumab deruxtecan group and 24% of the physician’s choice group), anemia (38% and 23%, respectively), and decreased white-cell count (21% and 11%). A total of 12 patients had trastuzumab deruxtecan-related interstitial lung disease or pneumonitis (grade 1 or 2 in 9 patients and grade 3 or 4 in 3), as adjudicated by an independent committee. One drug-related death (due to pneumonia) was noted in the trastuzumab deruxtecan group no drug-related deaths occurred in the physician’s choice group.
Conclusions: Therapy with trastuzumab deruxtecan led to significant improvements in response and overall survival, as compared with standard therapies, among patients with HER2-positive gastric cancer. Myelosuppression and interstitial lung disease were the notable toxic effects.