The VELIA trial, which is also known as GOG-3005, is a randomised phase III trial, placebo-controlled, in patients who are newly diagnosed with ovarian cancer. It is looking at the role of chemotherapy plus a PARP inhibitor in two different ways. One is to look at it in combination with chemotherapy alone and then followed by a maintenance phase of placebo and the primary experimental arm which is to give it in combination with chemotherapy and then continue as maintenance. At this meeting we’re going to be talking about the primary endpoint which is to look at the progression free survival of patients who get veliparib throughout chemotherapy and in maintenance as compared to what would be standard of care chemotherapy.
We’re very excited because this is the first trial to actually assess the merit of a PARP inhibitor given with chemotherapy. This has been a facet of clinical trial development that we have tried to do but because of the unique characteristics of veliparib, as compared to the other PARP inhibitors, this is the first that we’ve been able to actually give completely through chemotherapy and as maintenance.
The way that the study was designed was to actually look at its efficacy in three successively inclusive cohorts. The first cohort were patients who were noted to have a mutation in BRCA either in the germline or in the tumour. The second cohort was to look at all patients who had homologous recombination deficiency which includes the patients who have a BRCA mutation but also have a non-BRCA alteration showing the tumour having homologous recombination deficiency. Then the third population is the intent to treat population, so everybody.
In the trial we randomised 757 patients between those two arms. They were equally balanced on a number of our prognostic features. What we found was that the efficacy in each of those subgroup cohorts I just mentioned was positive. It was strongest in the BRCA patient population where the hazard ratio was 0.44. It was intermediately but very significantly positive in the patients who had HRD at a hazard ratio of 0.57. Then in the patient population which included all comers it was 0.68. So this is, as I mentioned, the first phase III randomised trial to actually show that you can give a PARP inhibitor with chemotherapy and when you continue it during maintenance therapy you benefitted all women who had an initial diagnosis of stage 3 and 4 primary cytoreduction and neoadjuvant chemotherapy followed by interval cytoreduction patients with ovarian cancer.
And to summarise, a message for doctors watching this?
Do what now?
A message to doctors?
Yes. The message from this meeting today is that the frontline standard is going to change again, which we’re very excited to see. The message from this particular study is that consideration of a PARP inhibitor at the time of initial diagnosis should be made and these data help to show that it’s safe and effective to do so.
PARP inhibitors for a long time have been known as single agents to have what we call a class effect on GI toxicity and a slightly differential effect on haematological toxicity. What we saw in the study was that where that was given as a single agent as maintenance we saw a very similar profile to all the other PARP inhibitors that have been given in multiple different clinical disease settings. What was interesting was that we gave it with chemotherapy; unlike our previous experiences with doing PARP with chemotherapy we were able to achieve clinically relevant, essentially full dose, chemotherapy in combination with the PARP inhibitor. What we saw during that time-point to say it’s safe was that we looked at the hematologic toxicity, which is one of the things you’d be most concerned about with PARP inhibition given during chemotherapy, and we saw that essentially in all of the parameters it was about the same with the exception of thrombocytopenia which was higher, although it was a low frequency it was higher and of greater grade. So we still have that particular aspect to consider. But when we looked at the total treatment discontinuations and the total number of dose reductions we didn’t see a difference between the three arms of the trial.