Lenvatinib–Pembrolizumab Combo Promising for Treatment of Endometrial Cancer

Results from a phase 2, single-arm, open-label clinical trial suggest that lenvatinib plus pembrolizumab is a novel combination therapy option for patients with advanced recurrent endometrial cancer (Lancet Oncol. 2019 Mar 25. Epub ahead of print).

“Lenvatinib is a multikinase inhibitor of VEGFR1, VEGFR2, and VEGFR3, and other receptor tyrosine kinases. Pembrolizumab, an antibody targeting PD-1, has moderate efficacy in biomarker-unselected endometrial cancer,” lead investigator Vicky Makker, MD, Memorial Sloan Kettering Cancer Center, New York, and colleagues explained.

“We aimed to assess the combination of lenvatinib plus pembrolizumab in patients with advanced endometrial carcinoma, after establishing the maximum tolerated dose in a phase 1b study,” they said.

Between September 10, 2015, and July 24, 2017, Dr Makker and colleagues enrolled 54 patients with metastatic endometrial cancer at 11 centers across the United States. Patients were given lenvatinib 20 mg daily plus pembrolizumab 200 mg every 3 weeks until disease progressed, unacceptable toxicity occurred, or patient withdrawal took place.

For this interim analysis, the percentage of patients with objective responses at week 24 in the per-protocol population was the primary end point. Ultimately, all but 1 of the enrolled patients was included in the analysis (n = 53).

As of December 15, 2017 (the cutoff date for antitumor activity data), the median follow-up time frame was 13.3 months. Overall, 21 (39.6%; 95% confidence interval, 26.5-54.0) patients had objective responses at week 24.

Hypertension, fatigue, diarrhea, and hypothyroidism were the most common treatment-related adverse events of any grade reported in the study, occurring in 58%, 55%, 51%, and 47% of patients, respectively. Hypertension (34%) and diarrhea (8%) were the most common grade 3 treatment-related adverse events, and no grade 4 treatment-related adverse events were reported.

Notably, 5 (9%) patients discontinued therapy because of adverse events. Serious treatment-related adverse events occurred in 16 (30%) patients, and 1 patient died from treatment-related intracranial hemorrhage.

“Lenvatinib plus pembrolizumab showed anti-tumour 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,” Dr Makker and colleagues said.

“Lenvatinib plus pembrolizumab could represent a new potential treatment option for this patient population, and is being investigated in a randomised phase 3 study,” they concluded.—Hina Khaliq