New Biological Insights and Recent Therapeutic Advances in the Management of Acute and Chronic Leukemias and Myelodysplastic SyndromesRecent clinical data with the polo-like kinase inhibitor volasertib in elderly patients with AML
2:53 minutes.
TRANSCRIPTION:
DR LOVE: So Doug, just to finish out on AML, there is an agent, volasertib, that’s on a breakthrough designation with the FDA. Can you talk about what we know about volasertib and the most recent data we have on this? DR SMITH: It’s a polo-like kinase inhibitor, and it is a drug that’s shown some activity. And it’s been studied in combination with low-dose ara-C. So the study really was older folks with AML, and they were unfit for traditional chemotherapy. And then they were randomized between getting low-dose ara-C plus or minus the volasertib. Again, the response rates, 31% was presented, low-dose ara-C alone about 10% to 15%, no surprise to us. But adding the drug seemed to improve the response rate. Median event-free and overall survival were improved as well with the addition of the drug. Now we’re starting to fall into the category of a solid-tumor excitement response. Right? Two or 3 months of improvement. And yet for leukemia patients, even the ability to get into a remission is important, because many, many studies suggest that people do better and have other treatment options before them. Even folks who are unfit become fit with successful therapy and normalization of their bone marrow, providing other potential options for them. So again, while this is not a super-duper home run from the standpoint of this therapy, it is moving us toward the Holy Grail of getting something for older, unfit patients that can get them into remission and offer us some treatment options. DR LOVE: Hagop, there’s another big randomized trial out there in older patients. Where do you think this is heading? DR KANTARJIAN: The problem is the control arm is low-dose ara-C. And now that we’ve moved to azacitidine and decitabine being the standard of care, when the study comes out and if it’s positive, there’s going to be questions about would the combination with aza or decitabine be more favorable? So we need to do the pilot studies with volasertib and the hypomethylating agents to set the pace for the future studies. DR LOVE: Any more comments about what a polo kinase inhibitor — what does it really mean? What is it? DR KANTARJIAN: It’s very similar to the aurora kinase inhibitors. Both the aurora kinase and polo-like kinase inhibitors break the mitotic spindle, and so they do not allow the cells to divide. So you get multi giant-form cells, and those cells die. And I think there is the possibility that polo-like kinase and aurora kinase inhibitors could be synergistic, but these are similar mechanisms. DR LOVE: Any specific toxicities of concern? DR KANTARJIAN: With the volasertib, not much. With the aurora kinase inhibitors, there’s a spectrum, depending on the one you choose. |