Abiraterone in patients with recurrent epithelial ovarian cancer
Dr Susanna Banerjee - The Royal Marsden, London, UK
The CORAL trial is the first phase II study of abiraterone in recurrent ovarian, fallopian tube and primary peritoneal cancer. There was an urgent need to improve and develop smarter treatments for women with recurrent ovarian cancer so I’ll tell you a little bit about the rationale here. The androgen receptor has been reported to be expressed in between 27-90% of epithelial ovarian cancer and it’s also been shown in preclinical studies that androgens can stimulate ovarian cancer cell line proliferation and that can be inhibited by anti-androgen approaches. However, clinically, in clinical trials so far, over the years, in the 1990s for example with drugs such as bicalutamide, the anti-androgen approach has been modest in terms of efficacy. However, with newer emerging treatments there is a rationale to further evaluate targeting the androgen receptor pathway for women with recurrent ovarian cancer. So one such drug is a drug called abiraterone and this is a CYP17 inhibitor which works by inhibiting this enzyme which then results in the downstream effect of reducing androgen and oestrogen levels.
How do you think that this research might push ovarian cancer forward?
There is a host, in my view there are a lot, of promising agents in development but not all the drugs are right for all the patients. So we’ve already heard at this congress the success of drugs called PARP inhibitors; we heard about niraparib in the phase III setting and also rucaparib in the ARIEL2 study and these are very promising approaches for a group of patients. The CORAL study looked at abiraterone in ovarian cancer and this was in an unselected population but also had the ability to look at the responses and clinical benefit in patients that had the androgen receptor.
The primary endpoint was objective response rate according to RECIST, which is a measure of radiological response, but also CA125 which is the tumour marker for patients with ovarian cancer. In this study there was one out of 42 patients that responded to abiraterone and that patient had androgen receptor positive disease. Based on the minimal response rate that we saw in this study the study did not proceed to the next phase. However, what was very important is that some patients derived disease stabilisation for longer periods. So, for example, 26% of patients had a clinical benefit rate, so that means response or disease stabilisation, at twelve weeks and 14% had more prolonged benefit at 24 weeks.
What we have learned from this study is that although the response rate was low, there may be a signal that some patients may be benefitting from this approach and we need to understand more about those patients. The patient that did respond had a rare form of ovarian cancer called low grade serous ovarian cancer where treatment options are limited and, in fact, I have a patient that has been on treatment since December 2014 who again has that same histological subtype. So these are anecdotal cases, this is early signs potentially of benefit in certain groups of patients. So what we need to do next is understand more about the biology of the androgen receptor and the significance of this receptor in ovarian cancer. It’s very important that we do the appropriate scientific and clinical studies to look further into this. There is an ongoing study of another androgen receptor targeted drug called enzalutamide with a group from Memorial Sloan Kettering and that is ongoing and it will be very interesting to see the results from that study and to see what we can learn. It’s difficult and it would be wrong to prematurely dismiss targeted anti-androgen approaches with these newer agents in ovarian cancer and this study has shed light on that topic.
Could wider collaboration help in reaching patients with rare tumour types?
There are already; for patients with low grade serous ovarian cancer, that’s a prime example of how we’ve collaborated internationally. There’s a study called the MILO study which was an international collaborative effort which we were involved in, specifically in women with low grade serous histology with a drug called a MEK inhibitor. There are other studies, for example the LOG study, again an international collaborative effort for women with low grade serous ovarian cancer. So it’s really important that we work internationally, in particular for patients with rare cancers. As I said with regards to the androgen approaches, the anti-androgen approaches, it will be very interesting to see the results with the enzalutamide study from the US group.