ESMO Asia 2025 | The future targeted therapies and ADCs in metastatic endometrial cancer

Well, I think one of the more mature roles may be from PARP inhibitor because there’s already been one study like the DUO-E study, which was already been published. And then there’s also one ongoing FACE-3 trial, the RUBY-2 trial, which we had to post her presentation last year, I think. But the final results were not available yet. To be honest, the combinations of PARP inhibitor together with the immunotherapy, there’s some roles in non-MMR patients, but the hazard ratios overall speaking was only around 0.7 in both studies. And there’s still no overall survival benefits as such. Then some studies like the DUO study also performed some subgroup analysis, trying to look at the combinations of PARP inhibitor together with immunotherapy. And then they try to see whether there’s any benefits in any subgroup. And then, for example, for the DUO study, they found that patients with HRR, homologous recombination repair genes, mutation patients, appear to have more benefits from these combinations. And also some patients with like P53 abnormal expression and also serous carcinoma, it seems that the hazard ratios were also better compared to other subgroups. For example, for a patient with P53 abnormality, they found that the hazard ratio could be as low as like 0.47. And then for patients with HRR genes mutation, the hazard ratio could be as low as 0.25. So this is some support analysis from the DUO study. For the RUBY-2 trial, obviously it’s still, the final results were not available yet. But then for, well, from some preliminary data, we could see that for patients with P53 abnormality, the hazard ratio was around 0.3. So it seems that a selected group of patients with advanced endometrial cancer with MMR may benefit from this combination. So I think this regimen could warrant further exploration. And then there could be some other novel agents as well. For example, for patients with HER2 mutations or amplification, then there’s already some phase 2 trials trying to look at the benefits of like Herceptin together with chemotherapy. And then for the phase two trial, it could show some benefits in this situation. And currently, there’s also some other phase two, three trials trying to look at the benefits of adding like Takeda therapy as HER2, even as HER3. And also there’s some ADC ongoing like the DESTINY endometrial 0.1 or the NRG N24, which tried to examine the role of pembrolizumab together with some other agents like tadalafil and also carboplatin-paclitaxel. And tadalafil with regorafenib, we try to see which arm will be beneficial in patients with MMR, HER2-positive advanced metastatic endometrial cancer.

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