Lenvatinib Plus Pembrolizumab in Advanced Endometrial Cancer


Key Points

  • Objective response was observed in 39.6% of patients.
  • Median duration of response was not reached, with 83% of responses lasting ≥ 6 months.

In an interim analysis of a phase II study reported in The Lancet Oncology, Makker et al found that lenvatinib plus pembrolizumab was active in advanced endometrial cancer.

Study Details

In the study, 54 patients from 11 sites with metastatic endometrial cancer unselected for microsatellite instability or programmed cell death ligand-1 (PD-L1) status were treated with lenvatinib 20 mg daily plus pembrolizumab 200 mg every 3 weeks, with treatment continued until disease progression or development of unacceptable toxicity. Patients had received no more than two previous systemic therapies.

The primary endpoint of the interim analysis was the proportion of patients with investigator-assessed objective response at week 24 according to immune-related RECIST criteria in the per-protocol population (n = 53).

Response Rates

At the cutoff date for antitumor activity data in December 2017, median study follow-up was 13.3 months. Objective response at week 24 was observed in 21 patients (39.6%). Responses were observed in 5 (38.5%) of 13 patients with PD-L1–positive tumors, 6 (54.5%) of 11 with PD-L1–negative tumors, and 10 (34.5%) of 29 with unknown PD-L1 status. With a median follow-up for progression-free survival of 7.7 months (by which 51% of patients had disease progression or died), median progression-free survival was 7.4 months. Median duration of response was not reached, with 83.0% of responders having a response of ≥ 6 months and 64.5% having a response of ≥ 12 months.

Adverse Events

The most common treatment-related adverse events of any grade were hypertension (58%), fatigue (55%), diarrhea (51%), and hypothyroidism (47%). The most common grade 3 treatment-related adverse events were hypertension (34%) and diarrhea (8%). No grade 4 treatment-related adverse events were reported. Serious treatment-related adverse events occurred in 30% of patients. Treatment-related adverse events led to discontinuation of study treatment in 9% of patients. One treatment-related death was reported (intracranial hemorrhage).

The investigators concluded: “Lenvatinib plus pembrolizumab showed antitumour activity in patients with advanced recurrent endometrial cancer, with a safety profile that was similar to those previously reported for lenvatinib and pembrolizumab monotherapies, apart from an increased frequency of hypothyroidism. Lenvatinib plus pembrolizumab could represent a new potential treatment option for this patient population, and is being investigated in a randomized phase III study.”

Vicky Makker, MD, of Memorial Sloan Kettering Cancer Center, is the corresponding author for The Lancet Oncology article.

Disclosure: The study was funded by Eisai and Merck. The study authors’ full disclosures can be found at

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