(217) Outcomes of Reduced Dosing of Lenvatinib with Pembrolizumab for Advanced Endometrial Cancer

Poster Abstract:
Background/Rationale:
Endometrial cancer is the ninth most common cancer type in the United States. Recent cancer statistics reflect a lack of
improvement in survival rates of uterine cancers since the 1970s, indicating a need to explore treatment options.
Systemic platinum-based chemotherapy is the mainstay of recurrent disease, but alternative regimens have been
proposed for certain platinum-refractory patients. The 309–KEYNOTE-775 trial demonstrated longer progression-free
survival (PFS) and overall survival (OS) with lenvatinib and pembrolizumab compared to physicians’ choice
chemotherapy in patients with mismatch repair-proficient (pMMR) advanced endometrial cancer. However, lenvatinib
was discontinued in about 30% of patients and dose reduced in almost 67% due to adverse events. Thus, strategies to
improve lenvatinib tolerability while maintaining effectiveness outcomes have been employed by practitioners. In a
retrospective review at the University of Texas MD Anderson Cancer Center, How, et al. demonstrated that a lower
lenvatinib starting daily dose (14 mg) had fewer occurrences of dose reductions, longer time to treatment-related
toxicity, and no significant difference in PFS and OS compared to FDA-approved daily dosing for recurrent endometrial
cancer (20 mg) in the lenvatinib-pembrolizumab combination regimen. For hepatocellular cancer (HCC), Iwamoto, et al.
suggested that a “weekends-off” dosing strategy for lenvatinib provided patients better tolerability for drug-related side
effects, particularly fatigue. This strategy has yet to be explored in endometrial cancer, which sets the premise for this
study.

Objective:
To compare the safety and effectiveness outcomes between FDA-approved and reduced lenvatinib dosing strategies in
patients receiving lenvatinib plus pembrolizumab combination therapy for advanced endometrial cancer.

Methods:
This is a multi-site, retrospective, observational cohort study including adult members of Kaiser Permanente Northern
and Southern California who initiated lenvatinib plus pembrolizumab therapy for the treatment of advanced
endometrial cancer between September 1, 2019 and June 30, 2023. Patients were followed until end of membership,
death, or December 31, 2023, whichever occurred first. Patients were stratified into three cohorts based on initial
lenvatinib dosing regimen: lenvatinib 20 mg daily (Group 1), lenvatinib <20 mg daily (Group 2), and lenvatinib 20 mg
daily 5 of 7 days (“weekends off”) (Group 3). Group 1 was the control group, and Groups 2 and 3 were the study groups.
Effectiveness outcomes included 6-month PFS. Safety outcomes included the incidence rates of lenvatinib dose
discontinuation or dose reduction due to adverse events and of composite adverse events leading to lenvatinib dose
reduction and/or discontinuation.

Results: Pending.
Discussion/

Conclusions: Pending

References (must also be included in final poster):
1. Cancer of the Endometrium - Cancer Stat Facts. SEER. Published 2018.
https://seer.cancer.gov/statfacts/html/corp.html.
2. Siegel RL, Miller KD, Fuchs HE, Jemal A. Cancer statistics, 2022. CA Cancer J Clin. 2022;72(1):7-33.
doi:10.3322/caac.21708
3. National Comprehensive Cancer Network. NCCN Guidelines Version 2.2023. Uterine Neoplasms.
https://www.nccn.org/professionals/physician_gls/pdf/uterine.pdf. Accessed August 12, 2023.
4. Makker V, Colombo N, Casado Herráez A, et al. Lenvatinib plus Pembrolizumab for Advanced Endometrial
Cancer. N Engl J Med. 2022;386(5):437-448. doi:10.1056/NEJMoa2108330
5. How JA, Patel S, Fellman B, et al. Toxicity and efficacy of the combination of pembrolizumab with recommended
or reduced starting doses of lenvatinib for treatment of recurrent endometrial cancer. Gynecol Oncol.
2021;162(1):24-31. doi:10.1016/j.ygyno.2021.04.034
6. Iwamoto H, Suzuki H, Shimose S, et al. Weekends-Off Lenvatinib for Unresectable Hepatocellular Carcinoma
Improves Therapeutic Response and Tolerability toward Adverse Events. Cancers (Basel). 2020;12(4):1010.
Published 2020 Apr 19. doi:10.3390/cancers12041010