Lung cancer is the fifth most common cancer in Australia and the leading cause of cancer deaths, accounting for 20% of the total. There has been limited treatments for metastatic lung cancer previously, with chemotherapy being the mainstay of treatment. Five-year survival for stage IV lung cancer was 1%.
However, better understanding of lung cancer biology has resulted in many new treatments including immunotherapy and targeted treatment and as a result patient prognosis has improved.
Genetic mutations during cancer growth can lead to the initiation of neoantigens which can evade the immune system. Immune checkpoint inhibitors can amplify the host immune response to tumours, leading to durable response rates with a favourable safety profile.
Immunotherapy drugs can be used in various indications in first and second line settings. The pooled analysis of two Phase 3 trials (CheckMate-017 and -057) showed 58% of patients treated with nivolumab who achieved a complete or partial response were alive four years later. There is also emerging evidence that these drugs in combination with other drugs including chemotherapy can improve response rates in certain scenarios.
These drugs have very different side-effect profiles to chemotherapy. These side effects, termed immune mediated adverse events, arise from increased activity of the immune system and can affect any organ. If left untreated they can be life-threatening.
The most common side effects include fatigue, rash, colitis, pneumonitis, hepatitis and endocrinopathies. Corticosteroids are the mainstay of treatment for immune-mediated adverse events. Corticosteroids should be tapered over at least four to six weeks. Infliximab or mycophenolate may be considered in some toxicities that are not responding to high-dose steroids within 48-72 hours.
Some toxicities can occur even after cessation of immunotherapy. Clinicians should have a high level of suspicion of immune-mediated adverse events if new symptoms occur and early discussion with the treating oncologist is key to
Traditionally lung cancer was divided into non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC). Within NSCLC, the main subtypes are adenocarcinoma, squamous cell lung and large cell. Traditionally, this distinction has occurred to guide decisions on chemotherapy. However, there are some cancers with a driver mutation that are highly responsive to targeted treatments. These driver mutations include epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK) and receptor tyrosine kinase encoded by the ROS1 gene.
Agents targeting these mutations are oral, allowing patients the freedom to travel. These drugs often have high response rates. Over time, resistance can occur. Newer drugs, such as osimertinib, a third generation EGFR inhibitor, can overcome T790M resistance mutation following use of a first or second generation EGFR inhibitor.
- New treatment for metastatic lung cancer improves prognosis
- Be vigilant for side effects, which may be serious
- The challenge is to use these agents in earlier stages of disease
References available on request.
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Author competing interests: nil relevant disclosures.
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