Last month at the ASCO GI Symposium, Keryx and Aeterna Zentaris reported statistically significant benefit in survival from updated results of a randomized, double-blind, placebo-controlled phase II study of KRX-0401 (perifosine) for the treatment of advanced metastatic colorectal cancer.
The study was based on 35 evaluable, but heavily pre-treated patients, with relapsed or refractory metastatic colon cancer were randomized to receive capecitabine (Xeloda) from Roche at 825 mg/m2 BID on days 1 – 14 every 21 days plus either perifosine (P-CAP) or placebo at 50 mg daily (CAP).
The results showed that the P-CAP arm had 1 PR and 8 SD for an overall response rate of 64%, while the CAP arm had 0 PR and only 3 SD for a response rate of 27%.
In addition, looking at the overall survival, the data favoured the P-CAP arm a MOS of 15.3 weeks compared with 6.8 weeks for CAP alone.
Typical adverse events reported appeared to be relatively mild:
"The P-CAP combination was well-tolerated with Grade 3 and 4 adverse events of > 10% incidence for the P-CAP arm versus CAP arm as follows: anemia (15% vs. 0%), fatigue (0% vs. 11%), abdominal pain (5% vs. 11%), and hand-foot syndrome (30% vs. 0%)."
Perifosine is also being developed for the treatment of multiple myeloma, which is currently in phase III development. The compound is an inhibitor of Akt and phosphoinositide 3-kinase (PI3K), as well as other pathways such as JNK and MAPK. These pathways are associated with programmed cell death (apoptosis), cell growth, cell differentiation and cell survival as shown in the diagram below:
Source: Aeterna Zentaris
Interestingly, this morning's news brought an announcement that the FDA have granted Fast Track Designation for the perifosine in advanced, refractory colorectal cancer. Based on the phase II data, a randomised phase III trial is expected to begin this quarter based on a similar trial design.
Clearly, it will be a little while before the data is available, but definitely one to watch out for in the future given new therapy options are always needed in the refractory cancer setting.