KEYNOTE-146: A New Treatment Option for Advanced Endometrial Cancer - Episode 4

The Role of Lenvatinib Plus Pembrolizumab

Transcript:Vicky Makker, MD: With regards to how the recent breakthrough designation may impact how patients are stratified and treated in the clinic, I think for the moment, unless a patient is on a clinical trial, the initial backbone therapy for those who require systemic therapy is still carboplatin and paclitaxel chemotherapy for the majority of our patients. Should pembrolizumab and lenvatinib receive full approval? I believe that this would be the preferred second-line regimen for patients with advanced endometrial cancers that are microsatellite stable that warrant ongoing therapy.

With regards to how we think about patients, post treatment with pembrolizumab and lenvatinib in the advanced-disease setting, I think that depends on a myriad of factors. It depends on the patient’s histology, it depends on their molecular phenotype, and it also depends on their disease-free or treatment-free interval. So we’ll sort of take all of these as we discuss the response to this question.

For patients who have had a very long disease-free interval and who have excellent performance status, a platinum-based doublet would not be unreasonable in the recurrent or advanced-disease setting, post lenvatinib and pembrolizumab therapy. Other patients may be candidates for single-agent chemotherapy. I didn’t speak about this earlier when I spoke about the treatment of advanced patients with regards to chemotherapy, but we know that in chemotherapy-naïve patients, single-agent chemotherapy—including drugs like carboplatin, cisplatin, doxorubicin, liposome doxorubicin, paclitaxel, docetaxel, topotecan—are associated with a response rate in the 21%-to-36% range. So those would be viable options.

Hormonal therapy for patients who have low-grade, low-volume, indolent endometrial cancers would be a viable option. Bevacizumab, which is a monoclonal antibody that targets VEGF, would also be a viable option in the recurrent-disease setting. And of course there are a myriad of clinical trials that are available to our patients now, and based on their molecular phenotype, patients may be appropriate for various clinical trials. I think these are all appropriate ways to manage advanced recurrent endometrial cancer patients should the combination be approved in the second-line setting for the microsatellite-stable patient population. After that, these would be potential avenues of therapy.

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Transcript Edited for Clarity.