Novel Second-Line Treatment Strategies in Endometroid Adenocarcinoma

Video

Expert perspectives on second-line treatment approaches to endometroid adenocarcinoma, with deference to data from the KEYNOTE-775 clinical trial.

Transcript:
Matthew A. Powell, MD
: In this case, the decision at recurrence was to proceed with lenvatinib and pembrolizumab, and I certainly think that’s a very appropriate choice for this patient with proficient mismatch repair or microsatellite-stable endometrial cancer. There’s great evidence from the KEYNOTE-775 trial [NCT03517449] that this is an appropriate option for this patient.

Unfortunately, when these patients progress, we have to figure out what to do next. A lot of this sometimes will have to do with how long it has been since they were treated with their carboplatin-paclitaxel before, and the molecular profile of the cancer will help us determine therapies. Certainly, if they had prior immunotherapy, that would have an impact on our choices. For the most part, in [the] second and third line, [we’re] usually going with the regimen from the KEYNOTE-775 trial, which would be lenvatinib and pembrolizumab.

When we look further into the KEYNOTE-775 trial presented in several different major meetings by Dr Vicky Makker and published in the New England Journal of Medicine in 2022, this was a randomized, phase 3 trial design. So [it’s] our gold standard–type of study that involves the study arm, which was lenvatinib and pembrolizumab vs a standard-of-care chemotherapy. Those chemotherapies were at the discretion of the managing physician and were either doxorubicin or weekly paclitaxel. When we look at the results of the trial, there was overwhelming support for the combination of lenvatinib and pembrolizumab. We saw better response rate, [and] progression-free and overall survival, and really found that chemotherapy was not helping patients very much in this area. We found some very long-term nice duration of response for those patients who responded to this regimen. The exciting thing is that it worked across different cell types, where the serous cancer patients, which often have been our most difficult to treat [patients], were deriving benefit, as well as [were] endometrioid cases and clear-cell cancers. When we look at the efficacy data that really stands out, it’s across all the end points that this is a regimen that is benefiting patients. When we talk about counseling patients about this regimen, we do need to point out the safety and tolerability of the regimen. When people think of oral regimens, they think this should be easy. There can be toxicity, and it can be tricky to manage. One of the major issues we deal with is hypertension and GI [gastrointestinal] issues in the forms of diarrhea and other [adverse] effects. The tricky part [is that] diarrhea is usually not that difficult, but we often have to sort out if this could be an immune type of diarrhea, which is certainly managed differently when these patients have this problem. We’re very apt to have this patient doing a fairly intense monitoring of their blood pressure and then notifying us if they’re having trouble. Typically, if they develop diarrhea, especially early on, we’ll be holding the lenvatinib and if that resolves rather quickly, we can usually think that that was probably due to the TKI lenvatinib. If it’s persistent, then we have to be thinking about the possibility of an immune-related colitis. These are some of the facets of a 2-drug regimen. With more experience, when the [patients] are getting used to this, certainly dose reductions, dose delays, and dose holds are all very common. The nice thing is [when] we can get a patient on a dose that works for them. This can work for a long time for many of these patients.

Transcript edited for clarity.

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