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Testing for PIK3CA feasible; targeting treatment at pathway yielded good response
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International Conference on Molecular Targets and Cancer Therapeutics
Testing patients with cancer for mutations to the PI3K gene is feasible and may allow targeted treatment of the PI3K signaling pathway, according to the results of a study presented at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics.
“The implications of this study are twofold,” said Filip Janku, MD, PhD, a clinical research fellow of the University of Texas M.D. Anderson Cancer Center’s department of investigational cancer therapeutics. “We demonstrated that PIK3CA testing is feasible and may contribute to the decision-making process when offering a patient a clinical trial. Although this study suffers from low numbers, the response rate observed in patients treated with inhibitors of PI3K/AKT/mTOR pathway based on their mutational status was well above what we usually see in phase-1 clinical trials.”
PI3K is an enzyme that helps control cell growth; mutations to PI3KCA, the gene encoding the catalytic subunit of PI3K, have been found in many types of cancers. These mutations activate the PI3K-AKY-mTOR pathway.
Janku and colleagues conducted a mutational analysis of exon 9 and exon 20 of the PI3KCA gene using DNA from the tumors of patients referred for clinical trials using targeted therapies.
One hundred and seventeen samples were analyzed. The mutations were found in 12% of patients. In those cancer types with more than five tumors samples tested the mutations were most frequent in endometrial (43%), ovarian (22%), squamous head and neck (14%), breast (18%) and colon cancer (15%). No mutations were found in those patients with melanoma or cervical cancer.
Ten of the 14 patients found to have the PI3KCA mutation were treated with a drug that targeted the PI3K-AKT-mTOR pathway. Forty percent had a partial response to treatment. These responses only occurred in patients with endometrial, ovarian and breast cancers.
“These results are intriguing but at this point should be interpreted with caution,” said Janku. “The promising response rate needs to be confirmed in larger groups of patients. We expect to learn more as this project continues to offer PIK3CA screening to patients considering a phase-1 clinical trial.”
For more information:
- Janku F. #B134. Presented at: AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics; Nov. 15-19, 2009; Boston.
