Thank you for joining us today. Thank you for inviting me. You are the lead author on the new england journal of medicine paper on telud for breast cancer patients with a germline brca mutation. How was the idea for this trial even conceived? Well, the parp inhibitors have been shown to have a lot of efficacy in patients with brca mutations. So it really takes advantage of theyre already having a dna repair defect by having a mutation in that particular gene or genes, and and allows the dna not to repair itself in the cancerous cell, leading to the cell to die off. Now that has been seen. Pre, clinically and in phase one phase two – and this was the fda registration trial really looking at in comparison to standard of care. Chemotherapy a single agent pill, harp inhibitor once a day versus standard of care. Chemotherapies tell us about the design of the trial sure. So this trial was two to one randomized for uh talizopra, but one milligram orally daily versus physicians, choice of chemotherapy and they gave specific chemotherapies based on what was in the guidelines at the time that the trial was designed. It keeps cytobean gem cytobean vinoral, being a ribulin one of the big questions that we get and is that the trial did not have a platinum arm or a platinum comparison to the parp. Inhibitor and platinums have been shown to have a lot of efficacy in patients with a brca mutation.
So do we know how talisopriv compares to chemotherapy in terms of efficacy in this setting? Yes, so in this particular trial, and also we saw with the previous olympia trial, the parp inhibitors do have an improvement in progression free survival compared to the physicians choice of chemotherapy that were chosen in these trials. Now, at the time that we presented the imbraca trial, which is this trial, it was a larger study because it was powered to look at overall survival, but at the time of this first initial look at the progression free survival. Only 51 percent of the expected events had arrived, and so we did see a trend towards an improvement with a hazard ratio, but the data is not mature enough yet and well need to follow that through it hadnt reached statistical significance in that early look. So, in terms of toxicity and quality of life between the two groups, were there any meaningful differences? You know there really were as far as looking at quality of life measures, those patients on the parp inhibitor talozoprib did have improvements in quality of life compared to those on standard of care chemotherapy. We also have time to deterioration for these patients with metastatic breast cancer. Clearly, favored the talisopri as far as toxicities, the toxicities were different, the biggest toxicity that we see with talizobrib and the other parp inhibitors are anemia. These usually can be managed by dose delay, dose reduction and transfusion. Patients did have fatigue and some grade one alopecia compared to the standard of care chemotherapies.
They were similar, but depending on the chemotherapy that was chosen, for example, patients who were on cape cider being had more hand, foot changes versus you know neuropathy for some of the other chemotherapies. So, ideally, where should telesopra fit in the treatment sequence for patients with germline brca mutations? Well, i can speak for what i would do in my practice and what i do do for those patients with the brca mutation who have triple negative breast cancer. I have no qualms with using it right up front because we do see that people respond quite quickly. You know weve always been taught well. If someone has cancer thats in their liver, you need to go to chemo right away, but i dont think when we, i dont, think thats necessarily the case anymore and especially when we have time to treatment response being very similar going to the single oral agent. I think is very reasonable on the er positive patients and her to new normal. I think that targeting the estrogen receptor and the cdk inhibitors have had such profound effects. I tend to use those first, but when they become non responsive to endocrine therapy thats, when i would and thats when i would start to think about using a parp inhibitor, especially when im about to think about going to a chemotherapy. I think thats a very reasonable place to use it in the her2 positive breast cancers. The anti her2 therapies are so effective that i we really use the anti her2 therapies and this could possibly be considered once weve exhausted those options thats very exciting, but i do want to say that the umbraco trial and the olympia trial, looking at a laprab, did Not look in the her2 positive subset so really want to spend time targeting that her2 with the appropriate agents before our part.
Thank you. Thank you for joining us today. Thank you and thank you for watching this practice.