What is the recommended duration for continuing Lenvatinib (lenvatinib) and Pembrolizumab (pembrolizumab) in a patient with recurrent carcinoma of the uterine corpus (Ca corporis uteri), stage IIIC1, with progressive disease?

From the Guidelines

Lenvatinib plus pembrolizumab can be continued until disease progression or unacceptable toxicity occurs in this patient with recurrent endometrial cancer. For this stage IIIC1 endometrial cancer (pT3bN1aM0LVI2 G1) that has progressed after surgery, chemotherapy, and radiation therapy, the combination can typically be administered indefinitely as long as the patient is deriving clinical benefit and tolerating the treatment well, as supported by the KEYNOTE-775 trial 1. The standard dosing is pembrolizumab 200 mg IV every 3 weeks or 400 mg every 6 weeks, along with lenvatinib 20 mg orally once daily. Some key points to consider when administering this combination include:

• Regular monitoring should include imaging every 2-3 months, thyroid function tests, blood pressure checks, urinalysis for proteinuria, and assessment of side effects, as grade ≥3 AEs occurred in 70.5% of patients in the dostarlimab group and 59.8% of patients in the placebo group in the RUBY trial 1.
• Dose reductions of lenvatinib (to 14 mg, 10 mg, or 8 mg daily) may be needed to manage adverse effects while maintaining treatment.
• This combination has shown significant survival benefit in advanced endometrial cancer, particularly in patients with progressive disease after prior treatments, by combining lenvatinib's anti-angiogenic properties with pembrolizumab's immune checkpoint inhibition, with a median PFS of 6.6 months (95% CI 5.6 to 7.4) and a median OS of 17.4 months (95% CI 14.2 to 19.9) in the KEYNOTE-775 trial 1. The patient's quality of life and potential side effects should be closely monitored, and adjustments to the treatment plan should be made as necessary to balance efficacy with tolerability.

From the Research

Treatment Duration

• The duration of lenvatinib and pembrolizumab treatment can vary depending on the patient's response and tolerance to the therapy 2, 3, 4.
• Studies have shown that the median progression-free survival (PFS) for patients with endometrial cancer treated with lenvatinib and pembrolizumab ranges from 4.2 to 8.5 months 2, 3, 4.
• The median overall survival (OS) for these patients has been reported to be around 15.6 to 17.19 months 3, 4.

Dose Reduction and Discontinuation

• Dose reduction of lenvatinib is common due to adverse events, with one study reporting a median time to first dose reduction of 1.5 months 3.
• Discontinuation of lenvatinib and pembrolizumab due to adverse events has been reported in 7% and 11% of patients, respectively 3.
• Reducing the initial dose of lenvatinib may be better tolerated without compromising effectiveness, although the lower limit of effective dosing remains to be defined 2.

Safety and Efficacy

• The combination of lenvatinib and pembrolizumab has been shown to be effective in treating endometrial cancer, with an objective response rate of 36.5% and a complete response rate of 47% 4.
• However, the treatment is associated with a high incidence of adverse events, with 85% of patients experiencing all-grade adverse events and 39% experiencing grade 3 or worse adverse events 4.
• The efficacy and safety of lenvatinib and pembrolizumab in vulnerable patients, such as those with performance status 1-2, may be inferior compared to other patient populations 3.