No clinical benefit seen from adding perifosine to capecitabine in patients with refractory metastatic colorectal cancer
Phase III study did not reach primary endpoint despite earlier very promising data with perifosine
- Date : 20 Jun 2012
- Topic : Gastrointestinal cancers
Adding perifosine, an oral alkylphospholipid inhibitor, to oral capecitabine did not significantly change overall- or progression-free survival compared with capecitabine alone, according to data from the X-PECT study, presented by Dr Johanna Bendell of Sarah Cannon Research Institute, during the 2012 Annual Meeting of the American Society of Clinical Oncology (ASCO), 1-5 June, Chicago.
X-PECT is a phase III study that randomly assigned 468 patients with refractory colorectal cancer to receive perifosine/capecitabine (234 patients) or capecitabine (234 patients). In order to participate, patients were required to have colorectal cancer refractory to treatment with 5-fluorouracil, oxaliplatin, irinotecan, bevacizumab, and therapies that targeted wild-typeK-RAS. The primary endpoint of the study was overall survival. The median overall survival was 6.4 months and 6.9 months in two groups. The difference in overall survival was also not significant when analysed based onK-RASstatus. The difference in progression-free survival was not significantly different for patients in two arms of the study (10.9 weeks for combination therapy with perifosine and 11.4 weeks for capecitabine only). However, in a subset of patients with wild-typeK-RASwho discontinued oxaliplatin because of toxicity, combination therapy with perifosine was shown to significantly increase progression-free survival (18.1 weeks vs. 6.6 weeks; p = 0.003).
Biomarkers analysis may provide guidance on whether perifosine provides clinical benefits in a subset of patients
X-PECT study was undertaken based on very promising data observed in a small, phase II randomized study that included 38 patients. Overall survival was 17.7 months for patients receiving perifosine/capecitabine and 7.6 months for patients receiving capecitabine only (p = 0.0052). However, in that study, patients received perifosine combination as second- or third-line therapy and may not have been refractory to oxaliplatin or 5-FU. In contrast, patients enrolled in the X-PECT study had received a median between 4 and 5 prior therapies and had to be refractory to all currently available treatments. The phase II study was originally designed to test perifosine in seven tumour groups. When responses were seen in patients with refractory colorectal cancer, accrual of additional patients in the colorectal arm of the study was undertaken and the other arms of the study were closed.
New directions for treatment of patients with refractory colorectal cancer are needed. The clinical development of perifosine, which targets the AKT pathway, was undertaken based on the biology of colorectal cancer. Approximately 40% percent of patients with colorectal cancer show a deregulation of the PI3K/AKT/mTOR pathway.
The study researchers hope that an analysis of biomarkers may provide guidance on whether perifosine provides clinical benefits in a subset of patients. For the biomarker substudy, tumour biopsies before and after treatment are available from a subgroup of patients.
Thank you for rating!
You have already rated this page, you can only rate it once!