What are you trying to do with chronic lymphocytic leukaemia?
The RESONATE study is a confirmatory… and it’s actually the first randomised phase III study to be presented with ibrutinib comparing it to a standard comparator in relapsed and refractory and hard to treat CLL patients. Now the study included 391 patients, it randomised one to one of ibrutinib, the first in class oral BTK inhibitor, against ofatumumab, a standard therapy used in CLL. The results were really striking in that when you look at the primary endpoint, progression free survival, there was a dramatic difference early on. The six month progression free survival on ibrutinib was 88% versus 65% for ofatumumab. Overall survival, despite a crossover being allowed early in the therapy, was still observed with ibrutinib and the estimated survival at one year was 90% with ibrutinib versus 81% with ofatumumab. When you look at the survival curves, at nine months in the study where the crossover was allowed the comparator ofatumumab survival plateaus so that really shows how much ibrutinib is impacting both in the response, the progression free survival and the overall survival of CLL.
What do you make of the results so far?
The results are important because they confirm the efficacy of ibrutinib compared to a standard comparator for the very first time. For me, as a doctor that takes care of CLL, it says that with the exception of the very, very rare relapse and refractory CLL patient ibrutinib should be something that we’re considering for them.
Where does this fit in with the overall study?
These data clearly support the use of ibrutinib as a second line therapy. Clinical trials right now are on-going looking at ibrutinib in first line therapy and, if the results look as good in that setting as compared to what they look in relapse, what we hope is that in the future we’ll be treating CLL with a non-chemotherapy based treatment versus chemo-immunotherapy that we’re using now.
Are there markers to determine which patients are high risk and need this therapy?
Generally CLL is treated when patients are symptomatic and so that’s the criteria we would use. There are certain markers that predict that our traditional therapies won’t work and what’s really exciting about ibrutinib, one of those is the deletion 17p and ibrutinib works better as well against that group in terms of response and producing durable responses.
You are inhibiting Bruton’s tyrosine kinase. What effect does that have?
Bruton’s tyrosine kinase is part of the B-cell receptor signalling and what it does is it essentially strangles the cell from inside and prevents it from getting nutrition from the microenvironment on the outside of it. It causes the CLL cells to both stop dividing, proliferating, and it causes them to slowly die. Ibrutinib targets BTK very effectively, so you have a good target, it’s a good drug, and together you have something that’s transformative for CLL patients.
What does this mean for the busy cancer doctor?
For the busy cancer doctor we have a new transformative patient-friendly drug for CLL that, in the great majority of our relapsed patients, we should be considering over our other older options for this disease.
What is the take home message for the oncology community?
We should be considering ibrutinib in all of our relapsed and refractory CLL patients.