Centering discussion on safety and efficacy data from the GARNET trial, Bhavana Pothuri, MD, reflects on the role of dostarlimab therapy in patients with recurrent metastatic endometrial cancer.
Bhavana Pothuri, MD: The GARNET trial enrolled patients with recurrent endometrial cancer, and they were patients who had progressed on a prior platinum-based chemotherapy. These patients either had recurrent or advanced disease that was measurable. They were enrolled into 2 parallel cohorts. Cohort A1 was the dMMR [mismatch repair deficient] endometrial cancer cohort, and then cohort A2 was the mismatch repair proficient endometrial cancer. In terms of the primary and secondary efficacy outcome, let's start with cohort A, which was the dMMR or MSI-high [microsatellite instability-high]. The objective response rate was 43.4%, there was a 10% CR [complete response] rate and the disease control rate [DCR] was 55.7%. In the mismatch repair proficient cohort, the objective response rate was 11.5% and a DCR of 35.2%. I think the thing that's really notable is that the duration of response is really long with the treatment. That is really one of the biggest advantages with immunotherapy.
I'll start with the second question, what are the strategies that I use to mitigate and manage the side effects, and then I’ll get into the side effects. So, I think that these agents, the PD-1 inhibitors, are immunotherapy agents. So, while they work to kill the tumor cells, they can also affect essentially any part of your body. Educating your team as well as your patients is really important. I am a big believer in the team-based approach. My nurses, my nurse practitioners, and my clinical research team all are educated about the adverse events [AE] with immunotherapy. The most common side effects of dostarlimab are actually very manageable, such as nausea and fatigue. But the more important and severe side effects that one needs to be cautioned and concerned about are the immune related [IR] adverse events. Although they only occur in the grade 3 or greater, or only occur in about 5%, I think it's really important because early identification is key. So the early adverse events are usually things like rash and colitis. The later side effects [are] endocrine, so disorders of your thyroid and other endocrine AEs start at about 10 weeks or so and then can occur throughout the treatment. Then you have pneumonitis, which typically occurs between 12 and 20 weeks, and usually the liver adverse events occur late.
I think it's not just understanding that they can affect all these parts of your body, but really understanding the symptoms that are associated with this, and making sure your clinical team understands it, and your patient before they start the therapy understands it. I tell them to keep a log of their side effects and bring them in. I say pay close attention to some of the IR adverse events. So if you're having diarrhea then the nature of that diarrhea is important. If it is more bloody and mucusy, then it's more likely related to a colitis type picture. Pay attention to shortness of breath or cough, which can be a sign of pneumonitis. In addition, there are more rare ones where you can get an immune related pericarditis. We've all seen the kidneys being affected with nephritis and then commonly are thyroid, either hyper- or hypo-thyroidism. So it's really important to monitor your TFTs [thyroid function tests] during immunotherapy on a regular basis.
Transcript edited for clarity.