Characterization and Management of Adverse Reactions in Patients with Endometrial Carcinoma Receiving Lenvatinib plus Pembrolizumab (Study 111/KEYNOTE-146): Nurse Roles in Patient Education and Adverse-Reaction Management

November 2020 Vol 11, No 11
Krysten Soldan, RN
Memorial Sloan Kettering Cancer Center, New York, NY
Carolyn Johns, NP
Oregon Health & Science University, Portland, OR
Matthew H. Taylor, MD
Providence Cancer Institute, Portland, OR
Kathryn Gillis, PharmD
Eisai Inc., Woodcliff Lake, NJ
Robert Orlowski, MD
Merck & Co. Inc., Kenilworth, NJ
Min Ren
Eisai Inc., Woodcliff Lake, NJ
Vicky Makker
Department of Medicine, Memorial Sloan Kettering Cancer Center, Weill Cornell Medical Center, New York, NY, USA

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 ≥6 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. number: NCT02501096.


  1. Makker V, Taylor MH, Aghajanian C, et al. Lenvatinib plus pembrolizumab in patients with advanced endometrial cancer. J Clin Oncol. 2020;38:2981-2992.
  2. Lenvima [package insert]. Woodcliff Lake, NJ: Eisai Inc.; 2020.
  3. Makker V, Taylor MH, Aghajanian C, et al. Lenvatinib (LEN) plus pembrolizumab (PEMBRO) for early-line treatment of advanced/recurrent endometrial cancer (EC). J Clin Oncol. 2020;38(15 Suppl). Abstract 6083.
Related Articles
Assessment of Side Effects (SEs) Impacting Quality of Life (QOL) in Patients (Pts) Undergoing Treatment (tx) for Advanced Breast Cancer (ABC) in Clinical Practice: A Real-World (RW) Multicountry Survey
November 2022 Vol 13, No 11
To examine how SEs impacting QOL in pts with ABC are perceived.
Intracranial Activity of Tepotinib in Patients with MET Exon 14 (METex14) Skipping Non–Small-Cell Lung Cancer (NSCLC) Enrolled in VISION
November 2022 Vol 13, No 11
To provide analysis of the intracranial activity of tepotinib in patients with METex14 skipping NSCLC with BM from the VISION study to aid oncology nurse navigators who manage this population of patients.
MOMENTUM: Phase 3 Randomized Study of Momelotinib (MMB) versus Danazol (DAN) in Symptomatic and Anemic Myelofibrosis (MF) Patients Previously Treated with a JAK Inhibitor
November 2022 Vol 13, No 11
MF is a rare bone marrow cancer characterized by fibrosis, abnormal blood cell production, and dysregulated JAK/STAT signaling.1,2
Last modified: August 10, 2023

Subscribe Today!

To sign up for our print publication or e-newsletter, please enter your contact information below.

I'd like to receive:

  • First Name *
    Last Name *
    Profession or Role
    Primary Specialty or Disease State