Keytruda Combo Beneficial ‘Irrespective of PD-L1’ in Endometrial Cancer

Keytruda (pembrolizumab) plus chemotherapy improved survival in patients with endometrial cancer, according to findings from the phase 3 NRG-GY018/KEYNOTE-868 trial presented at the 2024 SGO Annual Meeting on Women's Cancer.

The drug combination tended to improve overall survival (time from treatment until death of any cause) and progression-free survival (time from treatment until death or disease worsening). Researchers observed these findings were seen across disease subtypes, including patients with DNA mismatch repair-proficient and -deficient disease, as well as those with or without PD-L1 positivity.

Keytruda is an immunotherapy drug that works by blocking the interaction between the PD-1 and PD-L1 proteins. In doing so, the drug eliminates the cancer cells’ ability to hide from the immune system. Interestingly, the NRG-GY018 trial demonstrated benefits from Keytruda regardless of their cancer’s PD-L1 expression, explained study author, Dr. Ramez N. Eskander, assistant professor of obstetrics, gynecology and reproductive sciences at the University of California San Diego Health.

“The relevance of PD-L1 molecular testing in endometrial cancer really has not been established, meaning the therapeutic information it may provide us to make a therapeutic decision has not been adjudicated or determined,” Eskander explained in an interview.

Transcript:

The relevance of PD-L1 molecular testing in endometrial cancer really has not been established, meaning the therapeutic information it may provide us to make a therapeutic decision has not been adjudicated or determined. There are some clinical trials, I will say the DUO-E trial, which suggested that utilizing their assay, which was a TAP score, may inform benefit, although when we looked at this and NRG-GY018, and [also] in prior endometrial cancer trials looking at immunotherapy, we didn't see that PD-L1 expression status informed efficacy. In the RUBY trial, when they presented data at this annual meeting, SGO 2024, similarly, they did not see that PD-L1 expression by a [combined positive score] informed the therapeutic benefit of immunotherapy.

So, at this time, there is no strong evidence that suggests that we should be using PD-L1 status to inform utilizing this combinatorial approach. In fact, I would argue that the strongest evidence we have from these trials suggests that the combination would be appropriate irrespective of PD-L1 expression.
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