The pairing of lenvatinib and pembrolizumab showed substantially superior effectiveness relative to chemotherapy in subjects with late-stage endometrial carcinoma (aEC), independent of MSI status or histological type, in cases where progression occurred post prior platinum-containing regimens, according to findings from Study-309/KEYNOTE-775. The tolerability profile for this dual therapy largely matched established patterns for the individual agents and for their use together in endometrial carcinoma plus various other malignancies. Given the frequent clinical challenges in aEC cases, the present work aims to profile major adverse events (ARs) linked to this regimen and summarize handling tactics, thereby delivering actionable advice on AR control to enhance oncologic gains and lower risks of therapy cessation. Within Study-309/KEYNOTE-775, subjects received lenvatinib (20 mg by mouth daily) combined with pembrolizumab (200 mg IV every 3 weeks) or chemotherapy (doxorubicin or paclitaxel). Rates of occurrence, average time to initial AR appearance, dosage changes, and supportive drugs are reported. Major ARs assessed comprise hypothyroidism, hypertension, fatigue, diarrhea, musculoskeletal disorders, nausea, decreased appetite, vomiting, stomatitis, weight decreased, proteinuria, and palmar-plantar erythrodysesthesia syndrome. Predictably, prevalent all-grade major ARs encompassed hypothyroidism, hypertension, fatigue, diarrhea, and musculoskeletal disorders. Severe (grade 3-4) major ARs affecting ≥10% of cases involved hypertension, fatigue, and weight decreased. Major ARs generally emerged in the initial approximate 3 months of therapy. Handling tactics for ARs aligned with product labeling and trial protocol are outlined. Optimal control of ARs during lenvatinib plus pembrolizumab therapy entails informing patients and the full care team, applying prophylactic steps alongside rigorous surveillance, and prudent employment of dosage changes plus supportive agents.
