Tohoku J. Exp. Med., 2024 February, 262(2)

Lenvatinib plus Pembrolizumab Combination Therapy for Advanced or Recurrent Endometrial Cancer: A Single-Center, Retrospective Analysis

Mikako Tochigi,¹ Shogo Shigeta,¹ Muneaki Shimada,^1,2 Shuko Miyahara,¹ Junko Hasegawa-Minato,¹ Yusuke Shibuya,¹ Masumi Ishibashi,¹ Chiaki Hashimoto,¹ Hideki Tokunaga¹ and Nobuo Yaegashi¹

¹Department of Obstetrics and Gynecology, Tohoku University School of Medicine, Sendai, Miyagi, Japan
²Tohoku University Advanced Research Center for Innovations in Next-Generation Medicine, Tohoku University, Sendai, Miyagi, Japan

A multi-kinase inhibitor, lenvatinib, plus an immune checkpoint inhibitor, pembrolizumab, became a viable therapeutic option for advanced or recurrent endometrial cancer in Japan by the end of 2021. The Japanese population has a relatively unique genetic background. Hence, the safety profile and effectiveness of lenvatinib plus pembrolizumab may differ between the Japanese and other populations. This single-center, retrospective study aimed to evaluate the treatment efficacy of lenvatinib plus pembrolizumab and the safety profile of the associated adverse events. The clinical records of 15 patients, who received lenvatinib plus pembrolizumab for advanced or recurrent endometrial cancer at the Tohoku University Hospital, were reviewed. Best overall response and disease control rates were 40.0% and 73.3%, respectively. Treatment was discontinued owing to disease progression and adverse events in six patients, respectively. As of the end of July 2023, treatment was ongoing in the remaining three patients. The median treatment and progression-free survival durations were 118 and 258 days, respectively. Relative dose intensity of lenvatinib was not positively associated with progression-free survival, neither during the first 4 weeks after treatment initiation nor during the entire treatment period. All patients experienced one or more adverse events, the most common of which were hypothyroidism (90%) and hypertension (83.3%). Among the 15 patients, 13 required lenvatinib dose reduction owing to adverse events. One patient developed grade 4 interstitial pneumonia requiring intensive care. Our results validate the short-term efficacy of lenvatinib plus pembrolizumab, and indicate that dose optimization of lenvatinib could be individualized without impairing efficacy.

Key words —— combination therapy; endometrial cancer; lenvatinib; pembrolizumab; relative dose intensity

© 2024 Tohoku University Medical Press

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Tohoku J. Exp. Med., 2024 February, 262(2), 85-95.

Correspondence: Shogo Shigeta, M.D., Ph.D., Department of Obstetrics and Gynecology, Tohoku University School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi 980-8574, Japan.

e-mail: shogo.shigeta.a4@tohoku.ac.jp