We’re very excited that the second PARP inhibitor for germline BRCA associated advanced breast cancer has now been approved by the US Federal Drug Administration as of October 16th when talazoparib was approved and it’s being evaluated by the European Medicines Agency that has accepted it for review. So that’s exciting because previously for a long time we had no approved PARP inhibitors which made no sense and then we had olaparib. So, as of this week, we now have two PARP inhibitors that are approved in this setting.
The EMBRACA trial actually provided the data that led to the approval, it was a registration study that randomised women with metastatic breast cancer who had received up to three lines of prior chemotherapy for metastatic breast cancer and had a germline BRCA1 or 2 mutation to receive either talazoparib or treatment of physician’s choice, which was standard chemotherapy agents. Again it was a two to one randomisation. One of my colleagues presented data from a subset looking at triple negative breast cancer and, similar to what we saw with the trial as a whole, progression free survival was significantly prolonged, not only in the group as a whole but also in the triple negative subset. It’s really striking to look at the difference in response which was dramatically higher with the PARP inhibitor than with the chemotherapy. But chemotherapy is generally cheaper than a new agent so a big consideration always is it really worth it and why give it, maybe we can just keep giving it later and later because chemotherapy is cheaper so why give the drug.
The second thing that comes up is that all of these trials excluded patients who had disease resistant to platinum salts because platinum chemotherapy resistance seems to have a similar mechanism as resistance to PARP inhibitors. So if you’ve already had disease progression on platinum your response rate and benefit from PARP inhibitors is not zero but it’s less than if you didn’t have that situation. So people have said, ‘Maybe we should use the platinum because it’s so much cheaper and not use the PARP inhibitor because we haven’t yet seen a survival benefit from those trials.’ But we presented, looking at the triple negative subset, data for patient reported outcomes and then there’s also my colleague, Dr Ettl, also published the PRO data for the entire study in Annals of Oncology. What’s really fascinating is that time to definitive deterioration, clinical deterioration, is dramatically longer with the PARP inhibitor than it is with standard chemotherapy agents, including vinorelbine, eribulin, capecitabine etc. Patients also had a decrease in many different symptoms associated with quality of life, functionality and just symptoms associated with breast cancer using a breast cancer specific scale. So either you got a whole lot better in terms of quality of life and global quality of life and functionality or you had much less deterioration in your symptoms. Then if you looked at time to deterioration on pain it also was dramatically longer with the PARP inhibitor than with standard chemotherapy.
So when you take that data as a whole, and there actually was data on the hormone receptor positive subset as well presented at the Young Women’s Conference in Lugano in the last week, it really suggests that not only are you having a better response and longer progression free survival with this drug but also patients are living a better quality of life – global quality of life, functionality and symptoms are better for these patients than if they are receiving standard therapy. So it really provides a lot of important supportive data which was highlighted at this meeting when we’re evaluating new therapies that is critical to have in order to make these choices.