Endometrial Cancer Treatment: A Shift Towards Personalized Care

Microscopic image of endometrial cancer cells - Generated with Google Gemini AI

A retrospective study investigated how doctors are treating advanced endometrial cancer in the real-world setting, focusing mismatch repair (MMR) and microsatellite instability (MSI) testing. MMR and MSI testing can help to guide treatment decisions.

Researchers looked at electronic health records from over 1400 patients diagnosed with advanced endometrial cancer between 2018 and 2023. While testing increased over this period, many patients were still not being tested, especially patients of Black and Latinx descent.

A lack of testing could mean that some patients may not have access to newer, more effective, targeted drugs.

In an interview with Targeted Oncology^TM, Bhavana Pothuri, MD, gynecologic oncologist at NYU Langone Health, discussed the findings from this study and importance of this research.

Bhavana Pothuri, MD

Targeted Oncology: What are some of the unmet needs among patients with endometrial cancer?

Pothuri: The unmet needs in endometrial cancer are in the recurrent setting and in the mismatch repair-proficient frontline setting. In the [mismatch repair-deficient (dMMR)] cohort of patients, we have immunotherapy in addition to chemotherapy, which has hazard ratios of 0.28 to 0.3. I think some of these therapies are curative. It has been remarkable. But I think the mismatch repair-proficient subgroup still had benefit, and that hazard ratio was 0.54. There is still room to improve in that subset of patients. Anything we can do to either add to the immunotherapy or beat those results would be beneficial in the frontline and in the recurrent setting.

Now that immunotherapy is becoming more utilized in the frontline setting, we do not really have any data in patients after the use of immunotherapy, so that becomes a critical and unmet critical unmet need for our patients. I was reflecting recently as I was seeing patients in clinic, and I have several patients who have stage IV endometrial cancer who are now alive 4 to 5 years later and are in need of subsequent lines of therapy. Fortunately, my patients were able to capitalize on incredible clinical trial opportunities. But that goes to show you that we need additional therapies for this disease. I think the more therapies we have post-[immuno-oncology (IO)] progression, the more impactful it will be, and I think you are going to see benefit for these patients. I have been seeing it in a clinical trial setting already.

What were you evaluating in your analysis?

This study [looked at] real-world treatment patterns and outcomes by mismatch repair and MSI status in patients with advanced and recurrent endometrial cancer over a 5-year period from 2018 to 2023. It was a retrospective database analysis. We used the Flatiron Health electronic record database. This captures over 280 US cancer clinics with 800 sites. We identified, during the study period, 1441 patients who were diagnosed with advanced or recurrent endometrial cancer and initiated frontline therapy during this time period. What we looked for was mismatch repair testing, and in addition, utilization of therapies in terms of novel, targeted therapies.

The reason we did this study was because new advancements in endometrial cancer have happened over the last 5 years. In the recurrent setting, we now have dostarlimab [Jemperli] and pembrolizumab [Keytruda] approved as single agents. In mismatch repair-proficient [disease], we have lenvatinib [Lenvima]/pembrolizumab approved in the recurrent setting. Now, in the frontline setting with the RUBY trial [NCT03981796], we have the addition of dostarlimab to chemotherapy. We also have [National Comprehensive Cancer Network] listing for both pembrolizumab and dostarlimab in the frontline setting, irrespective of mismatch repair status. We wanted to kind of get a get a feel for what providers are doing with this data and what the uptake of these new therapies are.

Can you summarize your findings?

Our findings were interesting in that we identified biomarker testing patterns increased over time. In the beginning of the time period, it was less than 60%. By the end of 2023, about 80% were getting mismatch repair testing. But the thing that was important there is that we still saw disparities in this testing, with Black and Latinx patients having lower odds of being tested. That raises a significant concern for us. It is important that everyone gets tested. That is for 2 reasons. One, we want to make sure that everyone who has access to these novel therapies is able to utilize them. So likely, if you are not going to test, you are not going to be able to utilize these therapies. And then the second reason is the mismatch repair testing is a screen for Lynch syndrome, so you can identify other cancers such as colorectal, urothelial. It is important to have this framework so that the patient can get screened,their family members can get tested, and [they] also benefit from screening and preventative measures.

One piece that is important is that in terms of our findings less than 50% of patients received these treatments. I think there is an education piece that needs to happen. Perhaps we need to think about some implementation science and ways to increase access for our patients. These are approved therapies that only less than 50% are accessing.

The other thing that is important is we also looked at HER2 testing. At the beginning of our period, this was just over 20%. By the end, about 60% were getting tested. I think we need to increase that too because now trastuzumab deruxtecan (T-DXd; Enhertu) is now approved in the recurrent setting for patients with HER2 positivity.

What do you see as the next steps in this research or potential applications of these findings?

I think the most important thing is education around the disparities in testing. I think every patient needs to be tested, at minimum with mismatch repair immunohistochemistry. We need to highlight the disparities in testing. Also, making providers aware that there exist these new FDA-approved therapies that patients can benefit from. Making progress and having new therapies is one thing, but then making sure our patients are accessing those therapies to benefit from them is equally, if not even more important.

REFERENCE:

Pothuri B, Thaker P, Tymejczyk O, et al. Real-world treatment patterns and outcomes by mismatch repair/microsatellite instability (MMR/MSI) status in patients (pts) with advanced endometrial cancer (aEC), 2018-2023. J Clin Oncol. 2024;42(suppl 16):abstr 5601. doi:10.1200/JCO.2024.42.16_suppl.5601