| Abstract: |
Background: Lenvatinib plus pembrolizumab demonstrated promising antitumor activity in endometrial carcinoma (EC) in a phase 1b/2 clinical trial (Study 111/KEYNOTE-146).1 In patients with previously treated EC that was not microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) (n = 94), the objective response rate was 38.3% (95% CI, 29-49) as assessed by independent radiologic review using RECIST v1.1.2 Among responders, 69% had a duration of response e6 months.2 Study 111/KEYNOTE-146 also identified several treatment-emergent adverse events (TEAEs). Among all patients with EC who were not MSI-H or dMMR, 85.1% experienced grade 3/4 TEAEs; 25.5% discontinued 1 or both study drugs because of TEAEs; 78.7% experienced a dose interruption of 1 or both study drugs because of TEAEs; and 67.0% experienced lenvatinib dose reductions because of TEAEs.3 Frequently, nurses are the first point of patient contact and play a pivotal role in patient education as well as the assessment and management of adverse reactions. Objectives: This analysis aims to characterize common adverse reactions and their respective management strategies in patients with EC who are not MSI-H or dMMR. Additionally, it seeks to highlight the key role of nurses in patient education and adverse reaction management within a multidisciplinary team. Methods: In Study 111/KEYNOTE-146, lenvatinib was administered orally at a starting dose of 20 mg/day and pembrolizumab was administered IV at a flat dose of 200 mg every 3 weeks (n = 94). Study protocol allowed dose reductions of lenvatinib only. This analysis focuses on the characterization of key adverse reactions based on incidence and known association with study treatments, and interventions for adverse reactions in EC that were not MSI-H or dMMR. Key adverse reactions included hypertension, musculoskeletal pain, fatigue, nausea, diarrhea, decreased appetite, stomatitis, vomiting, hypothyroidism, palmar-plantar erythrodysesthesia (PPE), and weight loss. Results: Median times (weeks [range]) to first onset of key adverse reactions (any grade) were: hypertension (2.1 [0.1-30.1]), musculoskeletal pain (2.4 [0.3-31.3]), fatigue (3.3 [0.1-118.4]), nausea (4.7 [0.1-143.1]), diarrhea (4.8 [0.1-55.0]), decreased appetite (5.1 [0.1- 37.4]), stomatitis (5.5 [0.6-29.1]), vomiting (5.9 [0.4- 96.6]), hypothyroidism (6.1 [1.0-43.1]), PPE (8.1 [1.1-70.9]), and weight loss (9.1 [2.1-124.3]). Of these, only fatigue and diarrhea led to withdrawal of lenvatinib (1% of patients each), and no key adverse reactions led to withdrawal of pembrolizumab. Fatigue most frequently led to dose interruption of lenvatinib (16%) and pembrolizumab (14%), and also most frequently resulted in lenvatinib dose reduction (24%). Conclusions: Many adverse reactions due to lenvatinib plus pembrolizumab occur within weeks of treatment initiation and are predictable and manageable. Nurses play a crucial role in patient education regarding the incidence and management of adverse reactions. Frequent patient assessments, judicious use of supportive care measures, and subspecialty consultation are highly effective strategies for the management of adverse reactions. A preemptive nursing approach that encourages frequent communication and active patient participation is critical to successfully and safely treating patients with combination therapy. Early identification and management of adverse reactions can reduce treatment interruption and/or lenvatinib dose reduction and improve patient outcomes. Disclosures: This study was sponsored by Eisai Inc., Woodcliff Lake, NJ, USA, and Merck Sharp & Dohme Corp., a subsidiary of Merck & Co. Inc., Kenilworth, NJ, USA. Medical writing support for the abstract was provided by Oxford PharmaGenesis Inc., Newtown, PA, USA, and was funded by Eisai Inc., Woodcliff Lake, NJ, USA, and Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. ClinicalTrials.gov number: NCT02501096. |
