(CHICAGO, IL) – Adding perifosine to capecitabine does not prolong overall survival (OS) among refractory metastatic colorectal cancer patients, according to results of a double-blind, placebo-controlled phase 3 study reported at the 2012 American Society of Clinical Oncology Annual Meeting.
Despite promising randomized phase 2 study data, the results of the randomized, double-blind, placebo-controlled phase 3 X-PECT trial, “shows no benefit in overall survival adding perifosine to capecitabine” for these patients, said lead author Johanna C. Bendell, MD, Sarah Cannon Research Institute, Tennessee Oncology, Nashville, TN.
Perifosine is an oral synthetic alklphospholipid that inhibits or modulates AKT, NFkB and JNK signal transduction pathways. An earlier trial had suggested that adding it to capecitabine may increase overall survival, prompting the phase 3 study, in which patients were randomized to receive capecitabine (1000mg/m2 orally twice daily for Days 1-14) with either perifosine (50mg orally daily; n=234) or placebo (n=234). Cycles were 21 days.
At a median follow-up of 6.6 months, the median Overall Survival (OS) was 6.4 months for the perifosine-arm patients and 6.9 months among placebo-arm patients; the difference was not statistically significant (HR=1.11;P=0.315, log-rank). Median progression free survival (PFS) was not significantly different between the perifosine and placebo arms (10.9 weeks vs 11.4 weeks;P=.75). Non-response rates in both study arms were 97%. K-RAS mutation status did not affect OS or PFS between the two study arms, Dr. Bendell said.
Grade 3/4 toxicities for patients taking perifosine were rare and included diarrhea (6.0%), anemia (2.1% ), neutropenia (0.2%) and thrombocytopenia (0.2%).
Biomarker analysis will be undertaken to determine if other subgroups of patients may benefit, Dr. Bendell said.