| Abstract: |
Introduction. The combination of lenvatinib with pembrolizumab demonstrated significant improvements in progression-free survival and overall survival in patients with advanced renal cell cancer compared with sunitinib in the CLEAR trial (Clinicaltrials.gov: NCT02811861). The aim of the study is to characterize the major adverse events (AEs) (preferred terms grouped according to regulatory review) associated with the use of the combination of lenvatinib with pembrolizumab, based on data from the CLEAR study, and to provide strategies to overcome them. Materials and Methods. The safety of the combination of lenvatinib with pembrolizumab was analyzed in 352 patients included in the CLEAR study. The most important events were selected on the basis of their frequency (>= 30%). The time to onset was estimated and approaches to their treatment were described. Results. The most frequent NIs were fatigue (63.1%), diarrhea (61.9%), musculoskeletal pain (58.0%), hypothyroidism (56.8%), and hypertension (56.3%). The >= III severity IJs reported in >= 5% of patients included hypertension (28.7%), diarrhea (9.9%), fatigue (9.4%), weight loss (8.0%), and proteinuria (7.7%). The median time to onset of the first symptoms of major NS was approximately 5 months (about 20 weeks) from the start of treatment. Strategies for effective management of NSAIDs included monitoring baseline values, changing the drug dose and/or prescribing concomitant medications. Conclusion. The safety profile of the combination of lenvatinib with pembrolizumab was consistent with the known profile of each of the 2 drugs used in monotherapy. AEs were considered manageable using approaches such as monitoring, dose modification, and supportive care. Active and timely detection of AEs and their treatment are important for patient safety and continuation of treatment. |
