Brian Rini, MD
The tyrosine kinase inhibitor (TKI) axitinib (Inlyta) has been standard in the management of advanced renal cell carcinoma (RCC) for about 5 years now, but the emergence of new agents has made some members of the oncology community concerned that its significance will be overlooked in favor of more recently approved treatments.
At the 2016 Kidney Cancer Symposium, Brian Rini, MD, professor of Medicine, Cleveland Clinic, presented on the continued role for axitinib in kidney cancer. Rini said axitinib is distinct from other agents, in part, because it is well tolerated. The drug has a short half-life of 4 to 6 hours. This allows greater flexibility with dose adjustments, which enhances toxicity management.
Rini says tolerability is one of the key reasons why axitinib is often the “combination TKI of choice” in trials examining regimens combining TKIs with PD-1/PD-L1 inhibitors, such as pembrolizumab (Keytruda) and avelumab.
In an interview with OncLive
at the Kidney Cancer Symposium, Rini discussed the current relevance of axitinib in the RCC treatment paradigm and its likely integral role in immunotherapy combination regimens on the horizon.
OncLive: Could you provide an overview of your presentation?
: Axitinib has been approved for about 5 years now in the refractory kidney cancer space and my talk today was highlighting some of the features that make it a good drug in that setting. It is a potent and selective VEGF inhibitor that has the ability to titrate the dose up and down, which effects the efficacy, as well as the tolerability. Its pharmacologic properties allow it to be fine-tuned to each individual patient, which is relatively unique among the oral agents and I think provides some advantages.
There is clinical data supporting its efficacy in that setting—large scale, phase III clinical trials. It also has a biomarker of hypertension that can sometimes can be used to guide therapy. I think from a balance of benefit and risk—which matters since these drugs, unfortunately, aren’t curative for patients—I feel it is an ideal choice in that setting.
What are some remaining questions concerned with this agent?
The optimal way to titrate—it’s been a question that I've been interested in for about a decade and the manufacturer has done a nice job of building it into development but still, I don't think we've figured it out precisely. We've started to look at other titrating schemes, more rapidly getting people to where they need to be but also more gradually—not taking big jumps as in the label, which I think is a problem for many people. That’s an area of ongoing effort and I think we’re closer to getting it right, it’s just taking a long time.
What are your thoughts on axitinib in combination therapy?
That is probably the most exciting aspect. Axitinib is being examined in combination with both avelumab, which is a PD-L1 inhibitor, and pembrolizumab, a PD-1 inhibitor. I think one of the reasons that it’s been the combination TKI of choice is that it is very well tolerated.