番茄社区

The recent European Society for Medical Oncology (ESMO) virtual meeting featured new research in sarcoma, rare cancers that begin in the bone or connective tissue.

In this exclusive 番茄社区 video, , director of the Sarcoma Oncology Program at Massachusetts General Hospital, offers his takeaways from the top studies presented at the meeting.

Following is a transcript of his remarks:

This year's ESMO abstracts on sarcomas were interesting, I think we learned a few things. So I'm going to present maybe five or six, maybe seven abstracts that I thought were interesting at this meeting.

One was a desmoid study where they did a retrospective look at 242 patients around the idea of the question whether being pregnant or being on oral contraceptive pills would increase your risk of bad outcome. And ultimately they , or soon, before, or after starting [oral contraceptive pills], and actually did not find that these patients had any worse outcomes than other patients who had sporadic desmoid. That's sort of reassuring in that we can now tell our patients who present with pregnancy-associated desmoid that they're likely to have just as good outcome, as long as we stick with standard of care.

So what is standard of care for desmoid? There was another and did a study of what happens if we start with observation as our main initial therapy for desmoid. And they found that of the 100 patients, 60 of 90 of them were stable, 20 of 90 of them actually had improved tumor or decreased tumor size, eight of them had complete disappearance of their desmoid, and only two out of 90 patients had disease progression. And so this study really supports our initial sense that when patients walk into our door with a desmoid tumor, we shouldn't jump to treat them or do some sort of aggressive surgery on them, because there's a good chance that they could be stable or decrease in size if we just observe them. And so they were just nice supportive observations with how we should practice treating desmoid tumors.

More into therapeutics, there was a in a cohort of patients with epithelioid sarcomas. Now these are sarcomas that have lots of SNF5, which is a chromatin remodeling protein, which leads to over activity of PRC2. And so by using this MAK683 inhibitor they were able to find that it can induce some partial remissions or stable disease in patients with this tumor. And so it offers us potential to have maybe a second drug in this class for epithelioid sarcomas.

There was a study looking at the [Keytruda] in patients with leiomyosarcoma (LMS) and UPS [undifferentiated pleomorphic sarcoma]. We know that pembrolizumab is active in UPS and this study again, showed that two out of two patients treated had a partial response. In LMS, they saw no partial responses, even with gemcitabine. And eight out of 11 patients had stable disease, which I would attribute more to the gemcitabine than the pembrolizumab. So it supports my previous suspicion that pembrolizumab is probably not a very good drug for leiomyosarcomas, but still has activity in UPS.

An interesting late-breaking result was a (Yondelis). Now, doxorubicin has been studied in many other trials with or without a second agent. The most famous one was doxorubicin with or without ifosfamide, which showed increased response rates, increased PFS [progression-free survival], but no benefit in overall survival. Likewise this trial, again showed increase in overall response rates of 38% in the combination versus 13% [with the] single agent. The PFS was 13.5 months in the combination versus only 7.3 months in the single agent. However, overall survival was not statistically different in the two cohorts, again showing us that the combination of doxorubicin and trabectedin does lead to higher response rates, but that does not in itself necessarily translate to a benefit in overall survival.

And then the last study that I thought was interesting was their ongoing , the CAR T-cell product by Adaptimmune targeting MAGE-A4 in patients with synovial sarcomas and myxoid liposarcomas. And here they show that the CAR T-cell therapy was relatively well tolerated, 13 out of 15 evaluable patients had evidence of response to treatment, and a few patients had a pretty significant response. So I think this continues to be a very active and exciting area of investigation for sarcoma subtypes that have common antigens, like the synovial sarcomas and myxoid liposarcomas that have MAGE-A4 or NY-ESO-1 as common antigens.

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