Synapse - Adverse events and oncologic outcomes with combination lenvatinib and pembrolizumab for the treatment of recurrent endometrial cancer

Adverse events and oncologic outcomes with combination lenvatinib and pembrolizumab for the treatment of recurrent endometrial cancer Journal Article

Authors:	Zammarrelli, W. A. 3rd; Ma, W.; Espino, K.; Gordhandas, S.; Yeoshoua, E.; Ehmann, S.; Zhou, Q.; Iasonos, A.; Abu-Rustum, N. R.; Aghajanian, C.; Green, A. K.; Rubinstein, M. M.; Makker, V.
Article Title:	Adverse events and oncologic outcomes with combination lenvatinib and pembrolizumab for the treatment of recurrent endometrial cancer
Abstract:	Objective: To evaluate adverse events (AEs) of combination lenvatinib plus pembrolizumab for the treatment of recurrent endometrial cancer (EC) and to assess outcomes by lenvatinib starting dose. Methods: We retrospectively reviewed patients with recurrent EC treated with lenvatinib plus pembrolizumab at our institution between 10/1/2019–11/30/2021. Starting dose of lenvatinib was defined as standard (20 mg) or reduced (10 mg/14 mg). AEs were manually extracted through chart review and graded using Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. PFS, overall survival (OS), and duration of response (DOR) were analyzed. Results: Forty-three patients were identified; median age was 67 years (range, 54–85). The most common histologies were serous (35%), endometrioid (23%), and carcinosarcoma (21%). Starting lenvatinib doses were 10 mg (n = 10), 14 mg (n = 10), and 20 mg (n = 23). Median number of cycles received was 8 (range, 1–42). Twenty-four patients (56%) required ≥1 lenvatinib dose reduction; 3 (7%) discontinued lenvatinib, and 1 (2%) discontinued pembrolizumab for intolerance or AE. Thirty-six patients (84%) experienced grade ≥ 3 AEs; hypertension, weight loss, anemia, fatigue, and thrombocytopenia were most common. The standard dose group experienced significantly shorter observed PFS vs the reduced dose group (P = .02). There was no difference in DOR (P = .09) or OS (P = .27) between the groups. Conclusion: In clinical practice, AEs associated with combination lenvatinib plus pembrolizumab were common and comparable to Study 309/KEYNOTE-775 findings. AEs were similar regardless of starting lenvatinib dose. Further dose optimization studies of lenvatinib plus pembrolizumab may be indicated in recurrent EC. Clinical trial data remain the gold standard to guide starting lenvatinib dosing. © 2023 Elsevier Inc.
Keywords:	endometrial cancer; immunotherapy; outcomes; adverse events; lenvatinib; pembrolizumab
Journal Title:	Gynecologic Oncology
Volume:	178
ISSN:	0090-8258
Publisher:	Elsevier Inc.
Date Published:	2023-11-01
Start Page:	27
End Page:	35
Language:	English
DOI:	10.1016/j.ygyno.2023.09.010
PROVIDER:	scopus
PUBMED:	37748268
PMCID:	PMC11186314
DOI/URL:	https://www.scopus.com/inward/record.uri?eid=2-s2.0-85171736830&doi=10.1016%2fj.ygyno.2023.09.010&partnerID=40&md5=03ca01a454e0df4610a96debb9578f77
Notes:	The MSK Cancer Center Support Grant (P30 CA008748) is acknowledged in PDF. Corresponding MSK author is Vicky Makker -- Source: Scopus