These findings are in keeping with the phase II data, which showed first that dose escalation reduced the proportion of patients having subtherapeutic axitinib blood levels, and second that patients achieving therapeutic blood levels had progression-free survival about twice as long as that in their counterparts who did not achieve these levels.
"Dose titration with axitinib serves to normalize plasma exposure. ... We’re not increasing their drug levels above what patients at 5 mg get, but rather their drug levels are catching up to what some patients are able to achieve without titration," Dr. Rini explained.
Thus, in AXIS, "as you would expect from the pharmacokinetic data in which there is normalization of axitinib drug levels for both of these groups, they have roughly equivalent clinical outcomes, both of which were superior to sorafenib in the second-line setting."
The new analysis also showed that with axitinib, progression-free survival was essentially the same for prior sunitinib responders and nonresponders; in contrast, with sorafenib, it tended to be longer for prior sunitinib responders.
For both trial drugs, progression-free survival on prior sunitinib appeared to influence progression-free survival on the trial drug. For example, in the axitinib group, it was 40% longer for patients whose duration of prior sunitinib response was at least 9 months vs. shorter than that (6.3 vs. 4.5 months).
The Genitourinary Cancers Symposium is sponsored by the American Society of Clinical Oncology, the American Society for Radiation Oncology, and the Society of Urologic Oncology.
Pfizer sponsored the AXIS trial. Dr. Rini disclosed that he is a consultant to and receives research funding from Pfizer. Dr. Cho disclosed that he has no relevant conflicts of interest.