ESMO 2025 | The emerging role of TKIs and ADCs in osteosarcoma

So to understand the topic, we have to underscore that there are no approved drugs, unlike in this meeting for everybody else, in bone tumors. The reason might be the complex genomics of osteosarcoma, the rarity, but that’s it. So in the talk today, I address several peculiarities of bone tumors, heterogeneity and the rarity, but also the tumor microenvironment. It’s now very, very clear that we need to reprogram the tumor microenvironment, which, since both Ewing’s sarcoma and also osteochondroma, they have a cold immune microenvironment, which actually has been shown very clearly to be associated with poor survival and in this context that we discussed of different approaches from tyrosine kinase inhibitors and new emerging treatments like adoptive therapy like antibody drug conjugates, so as tyrosine kinase inhibitors, the most striking news is that we witnessed a change of paradigm. From a relapse single agent study, in 2025, we will enroll treatment to placebo, more than 1,700 patients with osteosarcoma. Since two studies, one in the United States and one in Europe, we will use MTP, methotrexate, doxorubicin, and cisplatin in combination with cabozantinib in the United States or in sequence with cabozantinib in Europe. And I think it’s very fascinating because we will see that we can change something for our patients. And at the same time, there is a new drug very similar to cabozantinib, which targets MET and vascular endothelial growth factor receptor 2, but most specific and potent, which was developed for kidney cancer, which is zanzalitinib. And there is a phase two trial open in MD Anderson Cancer Center, which will tell us if we can outperform cabozantinib’s figures. To let you know, the median progression-free survival is still around six months, and the best objective response is 40% with apatinib, but no breakthrough agent was approved. So I think it’s very fascinating. And the really new agent that we have to talk about, it’s called the ARTEMIS-002 trial. This agent is B7H3, which is targeted by this antibody drug conjugate, which uses a linker to a topoisomerase inhibitor. And the phase two trial demonstrated in osteosarcoma for three patients an objective response rate of 20%, which is remarkable. But what is important is that a response was sustained with a median duration of treatment of 19 months, which is really huge in osteosarcoma. And based on these phase two study results, a phase three randomized trial is ongoing in China, but also in a global program in the United States. And this underscores how alliances between different countries are doable and it’s so, so important in the setting of rare tumors.

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