Furthermore, unmet needs remain in the treatment of NSCLC, including the development of resistance to targeted therapies and the fact that not all molecular subtypes are actionable to date. The availability of new therapies with differing modes of action is potentially confusing, not only for primary care physicians but also for medical oncologists. The ability to target tumours at the molecular level has led to a paradigm shift in the management of patients with these mutations. 2 The prognosis of NSCLC dramatically changed following the discovery of genetic alterations affecting oncogenes, called drivers, including epidermal growth factor (EGFR) mutations, anaplastic lymphoma kinase (ALK) rearrangement, ROS1 or RET rearrangements, MET mutations or amplification, as well as BRAF or HER2 mutations (see Figure 1). The most common class is NSCLC, accounting for 85% of all cases. Traditionally, lung cancer is subdivided based on histology: small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC) have completely different molecular and therapeutic profiles. Lung cancer is the leading cause of cancer mortality worldwide 1 and remains one of the major therapeutic challenges in oncology. Non-small cell lung cancer, targeted therapy, checkpoint inhibitors, immunotherapy Article: The challenge facing oncologists is identifying which therapy is best suited to the individual patient. Several other anti PD-L1 compounds such as atezolizumab, durvalumab and avelumab are also very advanced in clinical investigation, in monotherapy as well as in combination with immune priming phase activators anti-CTLA4 ipilimumab and tremelimumab, across all treatment lines. Immunotherapies currently available for NSCLC include the checkpoint inhibitors anti PD-1 antibodies nivolumab and pembrolizumab. More recently, immunotherapeutic approaches have been investigated in the treatment setting of NSCLC, and these may provide superior outcomes and have substantially better tolerability compared to chemotherapy. The growing availability of therapies targeting specific genetic alterations, such as epidermal growth factor (EGFR) mutations and anaplastic lymphoma kinase (ALK) rearrangements, have led to changes in the guidelines to reflect the need for molecular profiling. In the last decade, the emergence of targeted therapies has changed the treatment paradigm for non-small cell lung cancer (NSCLC).
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