The evolving genomic classification of lung cancer.
Bottom Line: The identification of these oncogenic drivers has led to the design of rationally targeted therapies that have produced superior clinical outcomes in tumours harbouring these mutations.These targets include FGFR1, PTEN, MET, MEK, PD-1/PD-L1, and NaPi2b.In light of the myriad new biomarkers and targeted agents, multiplex testing strategies will be invaluable in identifying the appropriate patients for each therapy and enabling targeted agents to be channelled to the patients most likely to gain benefit.
Affiliation: Genentech Inc, South San Francisco, California, USA.Show MeSH
Related in: MedlinePlus
Mentions: Lung cancer is a competitive landscape with many new drugs in development and several failed phase III clinical trials. To reduce the risk of further clinical trial failure, genomic testing of NSCLCs must be included alongside histological testing, such that candidate patients can be identified and treatment choices optimized. For example, non-mucinous bronchoalveolar carcinoma (BAC) is now classified as lepidic predominant adenocarcinoma (100% TTF1, ∼45% EGFR mutation-positive, 5% BRAF mutation-positive), while mucinous BAC is classified as mucinous invasive carcinoma (15% TTF1, ∼80–100% KRAS mutation-positive, 0% EGFR mutation-positive) 7,104. The potential impact of targeting different molecular targets or histologies within the context of historical ‘all-comer’ studies is illustrated in Figure 4; not only do the specific targeted subsets need to be considered in terms of their particular prognostic behaviour (EGFR mutation-positive patients do much better on both chemotherapy and EGFR TKIs than EGFR wild-type patients), but the impact of removing these patients from the remaining pool should also be considered if spurious interpretations of trial data are to be avoided.
Affiliation: Genentech Inc, South San Francisco, California, USA.