Following the August 2024 decision by the FDA to
The expanded FDA approval indicated dostarlimab plus carboplatin and paclitaxel, followed by single-agent dostarlimab for the treatment of adult patients with primary advanced or recurrent endometrial cancer. The regimen was previously approved in primary advanced or recurrent endometrial cancer that is mismatch repair deficient (dMMR) or microsatellite instability-high (MSI-H). The expanded approval was supported by data from the phase 3 RUBY trial (NCT03981796), which demonstrated that patients who received dostarlimab plus chemotherapy in the overall population achieved a median overall survival (OS) of 44.6 months (95% CI, 32.6-not reached) compared with 28.2 months (95% CI, 22.1-35.6) among those who received placebo plus chemotherapy (HR, 0.69; 95% CI, 0.54-0.89; 1-sided P = .002).1,2
“Based on [data from] the RUBY trial, we [can] use the dostarlimab with carboplatin/paclitaxel, followed by the dostarlimab maintenance in all comers, [including] patients [with disease] that is proficient mismatch repair [pMMR]or dMMR,” Chase explained in an interview with OncLive® during Gynecologic Cancer Awareness Month, observed annually in September. “We can use it for everybody, and that’s helpful in that we have more options for our patients.”
Chase is a professor of clinical obstetrics and gynecology in the Division of Gynecologic Oncology at The University of California, Los Angeles (UCLA) Health in Los Angeles, California.
In the interview, Chase discussed the current treatment landscape of the disease, additional data from the RUBY trial, and the significance of the awareness month.
OncLive: How do you typically treat patients with recurrent endometrial cancer?
Chase: When you have a patient with recurrent endometrial cancer, it’s helpful to know what the characteristics of their cancer are. These days, the biomarker profile of the endometrial cancer is important. Is it pMMR? Is it dMMR? Is it HER2 2+ or 3+? Is it p53 wild type or mutated?
It’s also important to know when their last therapy was and what their last therapies were. Have they gotten immunotherapy previously? Was their last chemotherapy 6 months ago, 3 months ago, or 12 months ago?
There are a lot of different factors that play into how you’re going to treat that recurrent endometrial cancer. Even 10 or 15 years ago, it was probably that we would just treat these patients all the same way, with the same chemotherapies, the same approach to sequencing and treatment. However, these days, we’ve been able to really refine the recommended treatments based on the biomarker profile and the patient’s previous therapies.
How do you determine whether to add chemotherapy to an immunotherapy regimen for patients with recurrent disease?
If this is the patient’s first recurrence, and let’s say the patient previously had radiation alone, meaning they didn’t get chemotherapy at all, they’re new to chemotherapy. In that situation with recurrent disease that’s not amenable to another surgery or to radiation treatment, that patient I would treat with carboplatin/paclitaxel, and I would consider the addition of immunotherapy. The addition of an immunotherapy agent is very important for patients who are deficient in mismatch repair proteins. For patients that are dMMR, I would definitely approach that patient with treating them with carboplatin, paclitaxel, and an immunotherapy agent. There are two immunotherapy agents that are both anti–PD-1 antibodies. One is pembrolizumab [Keytruda], and the other is dostarlimab. I would choose between one of those to add to the carboplatin/paclitaxel in recurrent disease.
Now, it becomes a little trickier when the patient has already had chemotherapy. Let’s say they had carboplatin/paclitaxel, and this is their first recurrence, and they’ve been exposed to chemotherapy previously. In that situation, for a dMMR patient, if they’ve never had immunotherapy, it’s a no-brainer for me. I would give them carboplatin/paclitaxel, and I would add either dostarlimab or pembrolizumab. Now, if that patient is a pMMR patient and they’ve gotten carboplatin/paclitaxel before, your options are to give them carboplatin/paclitaxel again and possibly add an immunotherapy to that doublet therapy, meaning dostarlimab or pembrolizumab. Or there’s another option for those patients, which is to treat them with pembrolizumab and Lenvatinib [Lenvima]. Pembrolizumab plus lenvatinib is a non-chemotherapy option for that pMMR patient, and that’s helpful, because many times these patients who’ve gotten carboplatin and paclitaxel previously don’t want to get chemo again. They don’t want to lose their hair again. They don’t want to feel as tired or as sick—get neuropathy, for example. Those are the 2 considerations that might drive that patient to get lenvatinib and pembrolizumab.
The treatment of recurrent disease and adding immunotherapy to it depends on the patient’s profile. When was their last chemotherapy? What are their biomarkers? What are the tumor characteristics? What adverse effects did the patient have previously that they’re still potentially carrying from their last treatment?
What were the notable data from the RUBY trial?
RUBY was a randomized phase 3 trial, and the patients were randomized to carboplatin/paclitaxel with dostarlimab, followed by dostarlimab maintenance for up to 3 years, vs carboplatin/paclitaxel with a placebo, followed by a placebo for up to 4 years. One of the primary efficacy end points was OS and progression-free survival [PFS] in the all-comer group—so in everybody, dMMR and pMMR combined. Another primary efficacy end point was to look specifically at the dMMR patients and what their PFS was.
On that trial, we saw statistically significant improvements in both PFS and OS in the overall population, and we saw significant improvements in PFS in the dMMR group. What’s pretty incredible about the results is that once those survival curves start to separate, they maintain that separation. That difference between the 2 arms is maintained over time, and there’s now over 3 years of follow-up data to go by.
Other important characteristics of that trial are that it included high-risk histologies. It included carcinosarcoma patients, it included serous, it included clear cell, and it included mixed histologies, including dedifferentiated types. In addition, it included patients who had had chemotherapy only 6 months ago. The treatment-free interval had to be at least 6 months, but some of those patients had a relatively short treatment-free interval.
What else is interesting about the trial is that while most of the patients had to have measurable disease after surgery—for example, if it was a primary advanced, not a recurrent patient—if they had surgery, most of them had to have measurable disease. However, on the trial, there were some patients who did not have measurable disease. For example, if [a patient] had stage IIIC [disease] but they had a high-risk histology like carcinosarcoma, clear cell, or serous, they did not have to have measurable disease after surgery. Or if they had endometrioid type, and they had positive para-aortic nodes at the time of surgery, they did not have to have measurable disease. Unlike some of the other trials, there were some patients—not a ton of them, but some—with non-measurable disease.
How has the expanded FDA approval of dostarlimab affected your clinical practice?
For me, it’s a no-brainer to use it in a dMMR patient if they have advanced disease and this is their first treatment, or if they have recurrent disease and they’ve had either previous chemotherapy or not. For that dMMR patient, it’s a no-brainer for me to use carboplatin/paclitaxel and dostarlimab—or pembrolizumab, because that’s another option that we have.
For the pMMR patient, it becomes a little more nuanced. Although I have this option to use carboplatin/paclitaxel and immunotherapy—either dostarlimab or pembrolizumab—for the pMMR patient, it’s more of a shared decision-making process with the patient. Based on the GY018 trial, there was a significant improvement in PFS in the pMMR patients. Based on the RUBY trial, although it was an exploratory analysis, it looked like there was a significant improvement in PFS in the pMMR patients as well. Therefore, there is an improvement in outcomes in those patients. The question is whether or not that’s clinically significant, and that’s a discussion I’ll have with the patient: How much of a clinical benefit are they ok with to add this additional treatment to their regimen that might have toxicity? For the pMMR patient, it’s great to have options, but it’s more of a shared decision-making process.
What is the importance of recognizing Gynecologic Cancer Awareness Month, particularly regarding endometrial cancer?
It is Gynecologic Cancer Awareness Month in September, and it’s great that we have new therapies for our patients with endometrial cancer. It’s great that for some of our patients, we’re improving survival. Nevertheless, we also have to remember that it’s one of the cancers that’s on the rise. It’s the fourth most common cancer in women, but it’s on its way to surpassing colon cancer and become the third most common cancer in women.
In addition, it’s become even more deadly than ovarian cancer. It’s now in the top 10 most deadly cancers in women. We are seeing that certain patients are more likely to die of endometrial cancer than others. Raising awareness about the symptoms of endometrial cancer is important. Patients need to know, for example, it’s not normal to have bleeding after menopause—even if it’s just a spot or a pinkish discharge. That’s not normal. They should go see a doctor and tell them about their symptom, even if it’s just once.
It’s very important to educate postmenopausal women that any bleeding is abnormal post-menopause. For premenopausal women, if they’ve had a certain pattern of their menstruation their whole life, and that changes—like all of a sudden they’re having more bleeding or heavier periods or bleeding in between periods—that’s also a reason to go see the gynecologist. That’s not something to ignore.
I believe it’s important to spread the word about the symptoms so we can hopefully continue to see women present in an early stage as opposed to an advanced stage. Additionally, there is an association between obesity and endometrial cancer. Women who are obese, meaning they have a BMI over 30, are at higher risk for endometrial cancer. Anything that we can do to reduce obesity in the United States should hopefully also help reduce the accelerated incidence of endometrial cancer.
References
- FDA expands endometrial cancer indication for dostarlimab-gxly with chemotherapy. FDA. August 1, 2024. Accessed September 23, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-expands-endometrial-cancer-indication-dostarlimab-gxly-chemotherapy
- Jemperli. Prescribing information. GlaxoSmithKline; 2021. Accessed September 23, 2025. https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/761174s010lbl.pdf