Characterization and Management of Adverse Reactions From the CLEAR Study in Advanced Renal Cell Carcinoma Treated With Lenvatinib Plus Pembrolizumab

• Published in: The oncologist (Dayton, Ohio) Ohio), 2023-06, Vol.28 (6), p.501-509
• Main Authors: Motzer, Robert, George, Saby, Merchan, Jaime R, Hutson, Thomas E, Song, Xun, Perini, Rodolfo F, Xie, Ran, Bapat, Urmi, Puente, Javier
• Format: Article
• Language: English
• Subjects: Adverse and side effects; Carcinoma, Renal cell; Diagnosis; Drug therapy; Drugs; Genitourinary Cancer; Patient outcomes
• ISSN: 1083-7159; 1549-490X
• DOI: 10.1093/oncolo/oyac269

Abstract Background Lenvatinib plus pembrolizumab showed significantly improved progression-free and overall survival outcomes compared with sunitinib in patients with advanced renal cell carcinoma in the CLEAR study (NCT02811861). Here, we used CLEAR data to characterize common adverse reactions (ARs; adverse-event preferred terms grouped in accordance with regulatory authority review) associated with lenvatinib plus pembrolizumab and review management strategies for select ARs. Materials and Methods Safety data from the 352 patients who received lenvatinib plus pembrolizumab in the CLEAR study were analyzed. Key ARs were chosen based on frequency of occurrence (≥30%). Time to first onset and management strategies for key ARs were detailed. Results The most frequent ARs were fatigue (63.1%), diarrhea (61.9%), musculoskeletal pain (58.0%), hypothyroidism (56.8%), and hypertension (56.3%); grade ≥3 severity ARs that occurred in ≥5% of patients were hypertension (28.7%), diarrhea (9.9%), fatigue (9.4%), weight decreased (8.0%), and proteinuria (7.7%). Median times to first onset of all key ARs were within approximately 5 months (approximately 20 weeks) of starting treatment. Strategies for effectively managing ARs included baseline monitoring, drug–dose modifications, and/or concomitant medications. Conclusion The safety profile of lenvatinib plus pembrolizumab was consistent with the known profile of each monotherapy; ARs were considered manageable with strategies including monitoring, dose modifications, and supportive medications. Proactive and prompt identification and management of ARs are important for patient safety and to support continued treatment. Clinicaltrials.gov ID NCT02811861 This study used data from the CLEAR study to characterize common adverse reactions associated with lenvatinib plus pembrolizumab. This article reports management strategies for select adverse reactions.