Current and Future Treatment Paradigms in Second-Line Endometrial Cancer

At the 2022 Great Debates & Updates in Women’s Oncology virtual meeting, BJ Rimel, MD, Cedars-Sinai Medical Center, Los Angeles, California, shared new and exciting developments regarding second line treatments for patients with endometrial cancer.

In her presentation, Dr Rimel covered molecular testing and immunotherapy options that have changed the treatment paradigm for endometrial cancer and looked to the future at upcoming clinical trials.

Transcript

Hello. My name is BJ Rimel. I'm a gynecologic oncologist at Cedars-Sinai Medical Center in Los Angeles. I'm going to talk to you briefly about some updates in advanced and recurrent endometrial cancer. I'm very excited to tell you some of the things that are happening in this previously difficult-to-treat disease.

As most of you know, molecular testing in endometrial cancer has become the standard of care. We now expect and hope that everyone is availing themselves of at least [immunohistochemistry] IHC testing for microsatellite instability, specifically Lynch syndrome genes MLH1, MSH2, MSH6, and PMS2, to identify patients that may be microsatellite-high or microsatellite-instable, and thus be candidates for the therapies such as immunotherapy.

Immunotherapy was recently demonstrated to be an exciting opportunity for our cancer patients and specifically studied in advanced recurrent endometrial cancer. Patients who were noted to be microsatellite-instable or MSI-high were demonstrated to have a response to pembrolizumab in the study in the New England Journal. This set the stage for future testing. We now understand, through the work of Dr Vicky Makker [MD, Memorial Sloan Kettering, New York], that we have the opportunity to treat patients who are microsatellite-stable or -unstable with pembrolizumab plus lenvatinib, which is the biggest change to our standard of care in a long time, and now represents a second-line therapy that we didn't have previously.

The response rate in Dr Makker's study was approximately 37%. Most of the patients were able to stay on drug for 9 months or more, and it was statistically significant and a significant improvement over single agent non-platinum drugs, specifically doxorubicin and weekly paclitaxel, which were studied in that trial. What we are excited to think about is this new combination for patients that have a response. The drugs can be continued. In the study, they were continued for 24 to 36 months, as needed.

For patients that have a toxicity from the pembrolizumab or envatinib, it’s important to talk to the patients about their symptoms. Obviously, from the envatinib, we expect to see a lot of hypertension, which needs to be managed. We may see, also, diarrhea, which needs to be distinguished between the diarrhea caused by lenvatinib and the colitis that is a potential complication of pembrolizumab. Providers should be careful to ask patients about things, like whether there's blood or mucus in their diarrhea, or if they're having abdominal pain, which is a big distinction between the colitis caused by pembrolizumab or the diarrhea caused by lenvatinib.

We also know that lenvatinib can cause some other odd side effects, specifically palmar-plantar erythrodysesthesia, a finger, palm, and soles of feet rash. It can also cause a hoarse voice. It may also cause proteinuria, and these things should be evaluated for. Patients should have a dose reduction, if necessary, but ideally, we want to start out at the FDA-approved dose, which is 20 mg daily. This gives our patients the best opportunity for a response.

For patients that unfortunately do not have a response to lenvatinib and pembrolizumab, and we recognize that this represents about 60% of the metastatic recurrent population, other clinical trials are currently enrolling, and patients should be encouraged to consider participation. For patients that are thinking about future directions, we have recent data that some of our CDK4/6 inhibitors may be very useful, and that data is upcoming. There was also a recent phase 3 study looking at selinexor as an option for maintenance therapy that was also positive, and we look forward to seeing more of these in our armamentarium as we continue to treat patients with this difficult disease.

From Los Angeles, thank you. Have a great day.

Source

Rimel, B. Current and Future Treatment Paradigms in Second-Line Endometrial Cancer. Presented at: Great Debates & Updates in Women’s Oncology; Sep 21-23, 2022; Virtual.

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