Shannon Westin, MD, MPH, FACOG, a gynecologic oncologist at The University of Texas MD Anderson Cancer Center, discusses the use of durvalumab with or without olaparib for the treatment of endometrial cancers.
Shannon Westin, MD, MPH, FACOG, a gynecologic oncologist at The University of Texas MD Anderson Cancer Center, discusses the of using durvalumab (Imfinzi), a PD-L1 inhibitor, with or without olaparib (Lynparza).
The use of immune checkpoint inhibitors in endometrial cancer is driven by the 30% or so of tumors with microsatellite instability., says Westin. There is an opportunity for synergy between chemotherapy and immune checkpoint inhibitors like durvalumab. According to Westin, if given together, the tumor is more likely to respond to both.
Further, Westin explain that the addition of a PARP inhibitor, like olaparib, may also be highly beneficial. PARP inhibitors have already proven themselves highly active in certain cancers like breast and ovarian cancer, mainly due to homologous recombination deficiency. High levels of homologous recombination deficiency have been seen in endometrial cancers.
0:07 | The thing about endometrial cancer is for those patients that are diagnosed that early stage, it can be cured with really surgery and maybe just a little bit of additional Advent therapy like radiotherapy or chemotherapy. But for the remainder of the patients that are either diagnosed at advanced stage stage three or four, or have a recurrence, it can be really difficult to have a successful therapy. Now, the combination of chemotherapy, specifically paclitaxel, and carboplatin, as has been the standard of care for some time. But we have a need to really improve upon those outcomes, because we know in general, patients will not be cured from this regimen.
0:51 | Really, both of these populations are a huge unmet need. You know, those patients that do have advanced stage at diagnosis, they have a very high rate of recurrence. And so what we're trying to do is act early in their disease course, so that we can prevent that recurrence and hopefully achieve more cures. For the patients that have recurrence. It Again, it's very hard to cure these patients. And so this is an area where we have a lot of opportunity to improve outcomes.
1:26 | There has been quite a bit of activity of immune checkpoint inhibitors in endometrial cancer. Now, some of that is driven. Based on the prevalence of microsatellite instability, about 30% or so of patients will have that abnormality in their tumor. However, we do see that there is the opportunity for synergy between chemotherapy and immunotherapies, specifically checkpoint inhibitors like durvalumab. And so if we give the immunotherapy with the chemotherapy, then it makes it more likely to that the tumor will respond to both of those agents. And so that's the rationalization for utilizing it in a combination fashion. Now, we know that one of their ways that cancer tends to recur, or one of the mechanisms that it uses to be able to recur is evading the immune system. And so continuing an agent that will stimulate the immune system makes a lot of sense, once you have a complete response to therapy or response to therapy with chemo and so that's the the rationale for including the durvalumab both with the chemotherapy as well as a maintenance strategy. Now the addition of elaborate is very interesting, you know, PARP inhibitors have had a lot of activity and specific cancer types like breast cancer and ovarian cancer. And really, it seems to be mainly driven by homologous recombination deficiencies. And what we actually have found in our work is that and the mutual cancer has quite high levels of homologous recombination deficiency, both with mutations in the pathway as well as aberrations and other pathways like A-ROD 1A, so it would seem that upwards of about 50% of patients with endometrial cancer could stand to benefit and maybe even more with the addition of elaborate and so what we're doing is adding that elaborative as a potential our maintenance strategy for one of the arms.