Optimizing the use of lenvatinib in combination with pembrolizumab in patients with advanced endometrial carcinoma

Abstract

IntroductionThe combination of lenvatinib plus pembrolizumab demonstrated a relevant clinical benefit in patients with endometrial carcinoma. The safety profile was consistent with the established profiles of each drug in monotherapy, with the most frequent adverse events being hypertension, an on-target effect, hypothyroidism, diarrhea, nausea, vomiting, loss of appetite, fatigue, and weight loss.Areas coveredWe first review the rationale based on the combination of a VEGFR inhibitor and an immune checkpoint inhibitor, highlighting the main pharmacokinetic and pharmacodynamic features of lenvatinib. Next, we focus on the common adverse events associated with lenvatinib and guide how to optimally prevent, detect, and manage them, while minimizing interruptions during lenvatinib treatment.DiscussionThe side effects profile of lenvatinib is very well known, being similar across different tumor types. Most toxicities can be preventable. An appropriate, proactive, and thorough management of lenvatinib toxicities during treatment is required to maximize potential lenvatinib efficacy. Adverse events should be detected as early as possible, by both carefully monitoring the patient from lenvatinib initiation and preventing their occurrence. Patients should be followed also during treatment as some adverse events, e.g., cardiac dysfunction might appear later. Increased awareness on risk to benefit ratio among clinicians would be helpful to avoid dose interruptions or discontinuation of lenvatinib, with preferring other medical interventions and supportive care.

Analysis of East Asia subgroup in Study 309/KEYNOTE-775: lenvatinib plus pembrolizumab versus treatment of physician’s choice chemotherapy in patients with previously treated advanced or recurrent endometrial cancer

“…The most common grade ≥3 adverse events (AEs) in the combination therapy arm were hypertension (39.2%), decreased weight (10.8%), diarrhea (8.1%), and decreased appetite (7.6%) [ 12 ]. The safety profile of lenvatinib plus pembrolizumab was consistent with that reported in the phase 2 Study 111/KEYNOTE-146 [ 13 14 ] and those of the individual agents [ 15 ].…”

Small molecule targeted therapies for endometrial cancer: progress, challenges, and opportunities

“…It has FDA approval as monotherapy and in combination with other drugs such as pembrolizumab or everolimus in the treatment of various types of cancers, including differentiated thyroid cancer (DTC), renal cell carcinoma (RCC), hepatocellular carcinoma (HCC), and EC. 151 Numerous studies have been conducted to investigate the effectiveness of lenvatinib as a monotherapy for EC. For example, the Vergote group studied the use of lenvatinib as a second-line treatment for patients with recurrent EC in 2019 and the results showed that it had a modest antitumor activity with a 14.3% ORR.…”

“…It has FDA approval as monotherapy and in combination with other drugs such as pembrolizumab or everolimus in the treatment of various types of cancers, including differentiated thyroid cancer (DTC), renal cell carcinoma (RCC), hepatocellular carcinoma (HCC), and EC. 151…”