The Impact of Dostarlimab and Patient-Centered Outcomes in the RUBY Trial for Endometrial Cancer

In this interview, Dana Chase, MD, a gynecologic oncologist and professor at the David Geffen School of Medicine at the University of California, Los Angeles (UCLA) discusses the evolving landscape of endometrial cancer treatment. Drawing on insights from the RUBY clinical trial, Dr Chase examines how the addition of dostarlimab to standard carboplatin-paclitaxel chemotherapy offers significant improvements not only in progression-free and overall survival but also in quality-adjusted time without disease symptoms or treatment toxicity. She emphasizes the importance of patient-centered outcomes in clinical decision-making and shares perspectives on how these findings should inform real-world treatment pathways.

Dana Chase, MD: My name is Dr Dana Chase. I am a gynecologic oncologist. I'm a professor in the Department of Obstetrics and Gynecology at UCLA, specifically the David Geffen School of Medicine at UCLA.

How might the significant extension in quality-adjusted time without disease progression or treatment toxicity observed with dostarlimab influence clinical decision-making within endometrial cancer pathways?

Dr Chase: In a patient who has either metastatic advanced endometrial cancer or recurrent endometrial cancer, usually there are 2 considerations for these patients as they are starting treatment. One consideration is that these patients want to extend their lives, want to live longer, but they also want to be in remission longer. So, they want to have improved progression-free survival (PFS) as well as overall survival (OS). They want to see their disease shrink on the next CAT scan.

The second consideration is these patients want to not only have fewer symptoms from their metastatic or recurrent cancer, but they also want to have minimal additional symptoms related to the treatment that they're going to receive. It's different when you have a patient who is an early-stage patient without a lot of symptoms and who just wants to live longer, compared to a patient who has recurrent or metastatic disease and is experiencing symptoms from their disease. Those patients want to extend their lives, feel better, and see improvement in symptoms.

With the addition of new treatments like dostarlimab to standard-of-care chemotherapy for recurrent or metastatic advanced endometrial cancer, the idea is to extend the patient's life and PFS, but also to avoid introducing new toxicity and to improve disease-related symptoms. The introduction of dostarlimab into the standard of care has demonstrated both—an improvement in outcomes like PFS and OS for some patients and a positive impact on quality of life through a composite endpoint that considers time without toxicity and improvements in quality of life. When you have an endpoint that combines all of these factors, you can see the potential benefit of this new treatment.

Can you elaborate on how the RUBY trial's use of quality-adjusted time without symptoms of disease progression or toxicity (Q-TWiST) offers a more patient-centric evaluation of therapeutic benefit compared to traditional endpoints like PFS and OS?

Dr Chase: The Q-TWiST is an analysis that we can do on clinical trials, as long as the clinical trial includes patient-reported outcomes. It’s basically an integrated measure for patients with cancer that contextualizes the clinical benefit of improvements in OS and PFS with the effects of toxicity on patient-reported quality of life.

So, as opposed to just looking at PFS or OS alone, it also incorporates the effect of toxicity on the patient’s quality of life. It’s an important and more patient-centered outcome that provides additional insight into the real-world benefit of therapy beyond traditional treatment endpoints.

Given the consistent benefits of dostarlimab across mismatch repair/microsatellite instability subgroups, how should oncologists interpret and apply this data in real-world pathway stratification?

Dr Chase: In terms of appropriate patients for standard-of-care therapy—meaning platinum-based chemotherapy with dostarlimab—these days, all of our patients with endometrial cancer are tested for mismatch repair (MMR) deficiency. You can test patients based on immunohistochemistry or send their tumor for next-generation sequencing to get microsatellite instability (MSI) testing.

Based on that testing, we categorize patients as deficient in MMR or microsatellite instability-high, or proficient in MMR or microsatellite stable. Based on multiple clinical trials, including the RUBY trial, we see significant benefits from adding checkpoint inhibitors like dostarlimab to standard platinum-based chemotherapy. There is some effect in patients who are MMR-proficient as well.

When you look at the combined MMR-deficient and MMR-proficient groups, there are clear benefits in PFS and OS. However, when you separate the groups, the benefit is especially significant in the patients with MMR deficiency. In the MMR-proficient group, the benefit is more noticeable in PFS than in OS, although there might be a trend toward improved OS. Overall, the benefit is driven by the MMR-deficient population, though some PFS benefit is seen in the proficient group as well.

What role do you foresee for checkpoint inhibitors like dostarlimab in the upfront setting of endometrial cancer, especially considering the manageable toxicity profile demonstrated in the RUBY trial?

Dr Chase: The nice thing about the Q-TWiST analysis is that it considers not only how toxicity affects quality of life, but also how disease progression affects it. If progression happens sooner, that negatively impacts quality of life. The utility of incorporating checkpoint inhibitor therapy into standard-of-care upfront platinum doublet chemotherapy is that it delays progression without noticeably worsening quality of life. The addition of the checkpoint inhibitor to standard therapy, and then continuing it in maintenance, provides benefits without adding significant toxicity. It’s effective and well-tolerated.

How should institutions incorporate these findings into the development or refinement of clinical pathways to ensure alignment with both efficacy and quality-of-life outcomes for patients?

Dr Chase: First of all, it's always good to have more options for patients. For years, we've used carboplatin-paclitaxel as the standard of care for metastatic or first-line advanced endometrial cancer. While that regimen has been the standard for decades, it hasn't produced good enough outcomes in terms of PFS and OS.

Now, with the introduction of checkpoint inhibitor therapy like dostarlimab added to standard chemotherapy and then continued in maintenance, we're starting to see meaningful improvements. It’s important to incorporate this option into clinical pathways because it can delay progression and potentially improve survival for the right patient.

Additionally, this treatment doesn’t seem to add prohibitive toxicity or costs, which is important when considering health care utilization and patient experience. For the appropriate patient, this is an effective treatment that improves outcomes without significantly affecting quality of life or increasing treatment burden.