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Regorafenib (Stivarga) did not improve progression-free survival in patients with advanced or metastatic chordoma, according to the noncomparative phase II , which was presented at the recent European Society for Medical Oncology (ESMO) virtual meeting.

In this exclusive 番茄社区 video, medical director of the sarcoma program at the University of Southern California, describes the study results and explains why he is still encouraged by the study despite a negative finding.

Following is a transcript of his remarks:

My name is James Hu, I'm a medical oncologist here at the University of Southern California Norris Comprehensive Cancer Center. And I'm delighted to be here with you to discuss the recently presented REGOBONE study, specifically the chordoma cohort recently done at the ESMO meeting.

So, just very briefly, the REGOBONE study is a randomized phase II study looking at the effects of regorafenib compared to placebo in five different cohorts of bone sarcomas. And one cohort is the osteosarcoma cohort, which has been reported, the chondrosarcoma cohort which has also been reported, also the Ewing sarcoma bone cohort, and the CIC-rearranged bone sarcoma cohort.

And so this represents a study looking at a very rare tumor known as chordoma. And chordomas can be very, very indolent in their biological behavior. And they can also be very heterogeneous as well. Therefore it's important, in order to find a signal, to have a comparison group such as a placebo group that we have in this study.

I think another important point for this study is that the patients that had chordoma had to progress within 6 months before entering the study. In addition, these patients could have metastatic disease or they could have locally advanced disease as well. And also of interest is that patients could be enrolled if they had up to two previous therapies or none, so zero to two previous therapies were accepted into this study. I think an important exclusion criteria was that patients that had prior anti-VEGF therapies, such as sunitinib [Sutent] or Votrient [pazopanib], were not eligible for this study.

This was a randomized phase II study with a 2:1 design looking at the effects of regorafenib compared to placebo using progression-free survival at 6 months as the endpoint. The patient characteristics were well-balanced between the two groups. There was slightly more patients in the regorafenib group that had metastatic chordoma as compared to the placebo group. Also, the prior systemic therapies, there's about two out of the seven placebo patients actually received prior therapy and five out of the 16 patients randomized to regorafenib received prior therapy. And all of those prior systemic therapies were imatinib. So this is really, if you look at it, either patients that received prior imatinib or really no therapy. So, this is a very informative study for us.

With that, here are the results. The results basically demonstrated that at the 6-month time point, the progression-free survival was essentially the same, so 40%. So two out of the five patients in the placebo arm did not progress and six out of the 14, or 40%, in the regorafenib arm did not progress, so essentially equal non-progressive rate at 6 months, really no difference between the two arms.

The response rates: there were no response rates in this study in either arm, and the overall survival as a secondary endpoint, there was no difference as well. The median progression-free survival between placebo and regorafenib was 10.1 months and 8.2 months, respectively.

In conclusion, despite the fact that this was a negative study, I think for the sarcomatologist who sees a lot of these chordomas, I'm essentially encouraged because of the fact that we can do a randomized placebo-controlled study that's meaningful in a rare tumor such as chordoma.

In addition, there's other agents out there that show some promise. Brachyury, a type of transcription factor that's associated with chordoma, is overexpressed in these chordoma patients. And so therefore we could potentially take advantage of this unique antigen in developing a vaccine therapy or other types of immunotherapy to affect a response in these patients.

So the fact that we can do these randomized studies and accrue meaningful data, accrue numbers of patients that will give us meaningful data, is encouraging. And so there had been some vaccine brachyury-based therapies in clinical trials in the past that have demonstrated some interesting findings. We continue to look at this area of intervention for future systemic therapies. And I think it's also important to remember that clinical trials are important in deriving meaningful results, so that we can move forward in this rare, but very important, disease.

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