Treating NSCLC in clinical practice

This review aimed to provide updated guidelines on treating non-small-cell lung cancer depending on the genetic profile of the cancer. The authors conclude that in certain types of cancers with genetic mutations (changes) drugs aimed at the specific mutation could be more beneficial than chemotherapy and other treatments.

Non-small cell lung cancer (NSCLC) can be divided into two subtypes depending on the types of cells involved: squamous cell NSCLC and non-squamous cell NSCLC. Different drugs have shown different effectiveness on NSCLC depending on the subtype. Furthermore, there are common genetic mutations that contribute to cancer. These include a mutation in the epidermal growth factor receptor (EGFR) and the anaplastic lymphoma kinase (ALK) gene or the ROS1 gene joining to other genes. Specific drugs can target these mutations, increasing overall survival (time from treatment until death from any cause) and progression free survival (time from treatment until disease progression). Current studies are therefore aiming to determine the best type of treatment depending on the cancer genetic profile.

The authors reviewed several trials and discuss the current treatments for each NSCLC subtype.  

EGFR-positive mutations are common in non-squamous cell NSCLC. EGFR mutation testing is routine in clinical practice, particularly in adenocarcinomas. Current guidelines recommend EGFR tyrosine kinase inhibitors (EGFR TKI), such as erlotinib (Tarceva), as first-line treatment for this type of NSCLC. EGFR-TKIs have been shown to slow progression and improve quality of life compared to chemotherapy. EGFR-positive mutation NSCLC resistant to first-line EGFR-TKIs should be treated with third generation EGFR-TKIs, such as osimertinib (Tagrisso), combined with chemotherapy or local radiotherapy.

EGFR monoclonal antibodies, such as cetuximab (Erbitux) and necitumumab (Portazza), also inhibit EGFR. These can be considered along with chemotherapy as first-line treatment. Necitumumab combined with chemotherapy was found to increase survival in patients with EGFR-positive squamous cell NSCLC.

ALK and ROS1 mutations, commonly found in adenocarcinomas of the lung, benefit from treatment with the ALK and ROS1 inhibitor crizotinib (Xalkori).

Angiogenesis (development of new blood vessels) inhibitors, such as bevacizumab (Avastin), and immune checkpoint inhibitors (to prevent immune cells being blocked), such as ipilimumab (Yervoy), have been shown to have a survival benefit in several NSCLC. Ways to predict who will benefit most from these treatments have not yet been fully characterized.

This review concluded that the optimal treatment for NSCLC should depend on the specific genetic profile of the disease.

The authors highlighted the problems associated with tumor biopsies to provide genetic profiles and recommended further research into liquid biopsies (blood samples to detect tumor specific genetic mutations)