VIDEO: Combination treatments can increase compliance for PI3K inhibitors

Editor’s note: This is an automatically generated transcript. Please notify editor@healio.com if there are concerns regarding accuracy of the transcription.

There are several clinical trials that are currently active and in development using PIK3C inhibitors. So one of the issues we have with the increasing use of oral therapies is compliance.

So Victoria two is a first line study of the PIK3C inhibitor, Gedatolisib which is an intravenous pan PI3 kinase mTOR inhibitor that is given weekly along with oral CDK inhibitor, Ribociclib and Fulvestrant. So I believe this combination can really help with compliance in patients who are overwhelmed with a pit load.

Another limiting factor in the use of PIK3CA inhibitors is hyperglycemia. So the Amelia-1 study is examining the use of metallo protease inhibitor, evexomostat with Alpelesib or Capivasertib, which are the PIK3CA inhibitors and injectable Fulvestrant. And the use of this new drug is to see if hyperglycemia may be reduced and the use of oral anti-diabetic medicines can be reduced. So this would really expand the use of PIK3C inhibitors in patients with diabetes.

Some newer therapies have also shown great efficacy in early studies. The RLY-2608 allosteric PIK3C inhibitor has potent anti-tumor activity with minimal hypoglycemia and the STX-478 allosteric inhibitor, that also selectively targets mutant PIK3 kinase alpha and minimizes the wild type toxicities like the diarrhea hypoglycemia. So again, we look forward to seeing these drugs in development because they have CNS penetration, they're avoiding the toxicities that are the most concerning and they have shown good response rate in endocrine resistant disease.

In terms of other subsets of breast cancer, we know that PIK3CA mutation is most dominant in hormone positive breast cancer. But we also see these mutations in HER2 positive and triple negative breast cancer. So there are some active studies that are expanding the use of our current inhibitors. For example, Inavolisib with injectable Trastuzumab Pertuzumab in HER2 positive breast cancer. Alpelisib also with Trastuzumab Pertuzumab and also Alpelisib with chemotherapy NAB-paclitaxel in triple negative breast cancer.

So the future landscape of PIK3C inhibitors across the subtypes of breast cancer is very promising.