Mutations and other Biomarkers in advanced non-small cell lung Carcinoma with implications in the Philippine setting
- Author:
Joven Q. Tanchuco
1
,
2
Author Information
- Publication Type:Review
- Keywords: Targeted therapy
- MeSH: Carcinoma, Non-Small-Cell Lung; Mutation
- From: Philippine Journal of Internal Medicine 2019;57(3):175-193
- CountryPhilippines
- Language:English
- Abstract: Summary:Lung cancer remains a top cause of new cases and deaths from malignancies globally and locally. The development of targeted therapy for advanced non-small cell lung cancer (NSCLC), particularly adenocarcinoma, promises to improve survival significantly among suitable patients as compared to chemotherapy. About 50% of NSCLC patients have some driver mutations that can be treated by targeted therapy. The most common mutation is that involving EGFR which is found in as much as 90% of patients with driver mutations, most especially in those with adenocarcinoma, in women and never-smokers and those of East Asian ancestry. This is followed by patients with ALK or ROS1 rearrangements in another 5% each. Proper molecular profiling is, however necessary at the outset to identify patients who are suitable for targeted treatment. Fortunately, in the Philippines, testing for EGFR, ALK and ROS1 mutations are possible with several of the tyrosine kinase inhibitor drugs (TKIs) that target these mutations also available. A smaller proportion of patients have BRAF mutations (<5%) but the drug needed to treat this is not available commercially in our country. There are other mutations in advanced NSCLC which are considered potential drug targets for treatment. However, developing a clinically acceptable drug for use in lung cancer has been less successful. KRAS mutations, for example, can be as common as EGFR mutations (and sometimes more so) but no suitable drug for lung cancer has been identified yet. This is also true for METex14, HER2, VEGF, and others that are less common. Clinical studies continue to be done involving these target molecules. These biomarkers have sometimes found usefulness as indicators of poor prognosis and/or likelihood of developing drug resistance but for the most part, have remained in the realm of research. Immunotherapy was not included as a topic in this article. The search continues for new molecules to be used in targeted therapy for lung cancer. Development of drug resistance to TKIs, often inevitable and just a matter of time, continue to drive these development efforts. The remaining approximately 50% of NSCLC with no driver mutations also push efforts to search for appropriate drugs that will be good for them – including immunotherapy. Studies are also being done to look at various combinations of targeted therapy with chemotherapy and even immunotherapy. It will not be an overstatement to say that the future of lung cancer, especially NSCLC is rapidly evolving and will be creating data that may be very different from what we know at present. Clinicians who encounter and/or treat lung cancer should keep abreast of this rapidly changing information in properly advise their patients on suitable therapies. This is particularly true in financially constrained settings such as the Philippines where even just the cost of testing for these mutations can already be a significant barrier to whether or not to use targeted therapy.
- Full text:Mutations.pdf
