In a nutshell
This article reviewed published data concerning treatment options for patients who develop resistance to EGFR targeting drugs, such as erlotinib (Tarceva).
Some background
The EGFR gene is responsible for building a specific protein needed by cancer cells to multiply. Mutations (changes) in this gene lead to more aggressive cancers. However, these mutations also make the cancers more responsive to treatments with drugs that specifically target EGFR. These drugs are called EGFR tyrosine kinase inhibitors (EGFR TKIs) and include erlotinib (Tarceva) and gefitinib (Iressa).
In patients with EGFR mutations, EGFR TKIs are highly effective, leading to significant reductions in the size of the tumors. However, many patients develop drug resistance, with further cancer progression while undergoing treatment.
Methods & findings
The present article looked at treatment options available once drug resistance develops.
For patients with slow progression while treated with an EGFR TKI, researchers propose continuing therapy while maintaining careful clinical observation. Stopping the EGFR TKI drug may lead to a disease flare-up, with rapid tumor growth. Continuing treatment can prevent this and delay the need for chemotherapy.
In the case of brain metastases, radiation treatment was found to be especially useful, since EGFR TKI drugs only reach brain tissue in low concentrations.
Chemotherapy can be used either alone or in combination with EGFR TKI drugs. Most researchers suggest using platinum-based chemotherapy (containing cisplatin or carboplatin). This may be able to reduce the number of resistant cells and allow EGFR TKIs to maintain effectiveness. Several trials are ongoing to determine the best way to employ chemotherapy.
A number of targeted drugs are currently being developed to combat EGFR TKI resistance. These include second-generation EGFR TKIs, such as afatinib(Gilotrif) and dacomitinib, and third-generation EGFR TKIs, such as CO-1686 and AZD9291. These have shown promising results in early clinical trials.
Researchers also recommend obtaining new biopsy samples once the cancer progresses under treatment, in order to identify the reason for resistance. This may help personalize subsequent therapies.
The bottom line
There are a number of options available once resistance to EGFR TKI drugs develops. Several trials are underway to help identify the most effective strategies.
Published By :
Cancer
Date :
Apr 18, 2014
