Recent developments in understanding the biology of cancer has led to use of selective markers for determining treatment regimens in a number of tumour types, including CML, breast, lung and colorectal cancers and gastrointestinal stromal tumours. While this approach may be less good for the pharma companies if less revenues are generated in the short run, it is good news for patients who can receive tailored therapy targeted for their particular mutations without the test for a trial and error approach. So far, companies have encouraged this approach, believing that it will be a smarter strategy in the long run. The overall result is lower healthcare costs, higher response rates and hopefully, an increase in overall survival.
One of the earliest companies to realise the value of this targeted approach was Roche/Genentech, who used the HER-2 mutation to determine which patients would be most suitable for their HER-2 inhibitor, trastuzumab (Herceptin). Approximately 25-30% of women with breast cancer have the HER-2 mutation, which used to confer a poorer prognosis.
A new paper just released in the Journal of Clinical Oncology, suggests that a similar approach might be reasonable in breast cancer when determining which patients would be most likely to respond to bevacizumab (Avastin). Avastin inhibits angiogenesis, that is the formation of new tumour blood vessels that are essential for its survival.
To date, no biomarkers have been identified to predict outcome with the use of an antiangiogenesis agent for cancer. Vascular endothelial growth factor (VEGF) genetic variability has been associated with altered risk of breast cancer and variable promoter activity. The authors therefore evaluated the association of VEGF genotype with efficacy and toxicity in E2100, a phase III study comparing paclitaxel versus paclitaxel plus bevacizumab as initial chemotherapy for metastatic breast cancer.
The results were most interesting.
The researchers identified two genetic markers that appeared linked to improved survival in women with breast cancer given the medicine. Patients with genetic variations of VEGF-2578 AA and VEGF-1154 showed a better overall survival than those with alternative genotypes, according to an analysis of 363 tumor samples from a previous clinical trial.
Two other variants were linked to significantly fewer cases of high blood pressure.
Overall, the study supported an association between VEGF genotype and median overall survival as well as grade 3 or 4 hypertension when using bevacizumab (Avastin) in metastatic breast cancer.
However, the finding will need to be validated in other clinical trials. It is unclear if genetic tests might identify responders and non-responders in other tumour types (colorectal, lung, renal etc) where Avastin has activity, other than breast cancer. If the results are replicated even in breast cancer, new diagnostic tests will also need to be developed commercially to enable community oncologists to accurately determine which patients are eligible to receive Avastin therapy.