Current treatment options for advanced lung cancer in SA

Dr Sze Wai Chan clears up the complexity of understanding lung cancer and its treatment. 

Lung cancer is the leading cause of death worldwide. It’s the second commonest cancer in both sexes. It falls right behind prostate cancer in men and breast cancer in women.  

When patients are diagnosed with Stage 4 lung cancer, the prognosis is usually very poor (< 1 year with traditional chemotherapy). However, in the past 10 years, the development of targeted therapy and immunotherapy has changed the survival of these patients drastically.

Most lung cancers are caused by smoking (85-90% of patients). However, ‘never smokers’ can develop lung cancer, too. Never smokers’ lung cancers are unique as the cancer often has a driver mutation (changes in the DNA sequence of genes that cause cells to become cancer cells).  

Terminology talk

A lot of lung cancer patients are perplexed by the terminology used by their doctors. If you’re referring to the flowchart (below), these are the usual terms used and it’s important to know them, as each type and subtype of lung cancer is unique and treated very differently.

Firstly, we can divide lung cancer based on what they look like broadly under the microscope into non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC). 

Under NSCLC, they can look like squamous, or non-squamous (includes adenocarcinoma, large cell carcinoma and others). Besides what they look like under the microscope, we dive even deeper and find that they also have a DNA signature, so they are divided further into driver mutation and no driver mutation.

Mutations

Driver mutation is a unique change in the DNA of the lung cancer cell which ‘drives’ the cancer to grow. Some of these mutations have names, such as EGFR mutation, ALK or ROS1 mutation. These are best treated with targeted therapy, an oral drug that binds to these changes and kills the cancer directly. Some examples are erlotinib (EGFR mutation) and crizotinib (ALK or ROS1 mutations).

It’s important to know that targeted therapy only works if there is a mutation that can be targeted, otherwise the drug is completely useless. These mutations are often found in NSCLC of the non-squamous subtype, and in patients who never smoked or smokes very little. On average, the survival of patients on targeted therapy is at least 2-3 times more than chemotherapy.

Immunotherapy

Most NSCLC have no driver mutation (80%). Immunotherapy plays a big role here, either being used alone or in combination with chemotherapy.  The deciding factor is the PD-L1 expression, which is a simple counting of PD-L1 receptors on the lung cancer cells under the microscope. If the PD-L1 receptors are ≥ 50%, then single agent immunotherapy (anti-PD1) is usually enough to control the cancer (unless there are very extensive lung cancer involvements or rapidly progressive disease, then chemotherapy may need to be added). If the PD-L1 receptors are < 50%, then anti-PD1 immunotherapy won’t be enough to control the cancer and chemotherapy will need to be added.

In simple terms, anti-PD1 immunotherapy works by restoring your own immunity to kill cancer with your own white cells. The PD-L1 receptors are being used by the cancer to fool your immune system so that the cancer appears invisible to your body, therefore the cancer flourished. The more PD-L1 receptors there are on the lung cancer cells, the better the response when using anti-PD1 immunotherapy (pembrolizumab or nivolumab).

The beauty of restoring the immune system to kill cancer by itself is the potential life-long control of the cancer, as the immune system is clever to learn and remember how to protect the body. To date, using immunotherapy alone or in combination with chemotherapy has led to roughly double the response and double the survival, with some patients achieving long-term survival and control.  

Ask your oncologist about clinical trials to access the latest treatment and be part of the future treatment development.

Header image by Freepik