This is the fifth part of our series about the condition based on our patient booklet “Fast Facts for Patients: Non-small Cell Lung Cancer with KRAS Mutation”. This article explains KRAS-targeted therapies and how they work in non-small cell lung cancer (NSCLC).

If you have an NSCLC that has a KRAS mutation, this information will tell your doctor which treatment option is likely to work best for you. This section tells you more about KRAS-targeted treatment and other treatment options that are in development for KRAS-positive NSCLC.

KRAS-Targeted Therapies

At the time of writing there are two KRAS-targeted therapies that are approved for treating NSCLCs with a G12C KRAS mutation. These therapies are sotorasib and adagrasib. To have this treatment, you must have:

• an NSCLC with the G12C KRAS mutation
• cancer that has spread from the lung into nearby body tissues or to somewhere else in the body
• already tried at least one other type of ‘systemic’ treatment for your cancer spread (such as chemotherapy or immunotherapy).

Treatments that target other less-common types of KRAS mutations are also being researched. There are also ‘universal’ KRAS-targeted therapies in development. These may work across several different types of KRAS mutation. If you don’t have a G12C mutation in your lung cancer cells, your doctor may suggest having one of these treatments as part of a clinical trial.

How KRAS-Targeted Treatment Works

To understand how this type of treatment works, it may help to think of it as a switch that turns off the cancer’s ability to grow.

As we’ve seen, the cancer cells produce an abnormal form of the KRAS protein. This permanently switches on the cells’ drive to divide and multiply, causing the cancer to grow.

KRAS-targeted treatment acts as a block on the abnormal protein. It attaches (binds) to it and stops it from delivering the message telling the cancer cells to divide.

Commonly Used Words

You may hear your doctor talk about systemic therapy.

A systemic therapy is one that circulates through the bloodstream and treats cancer wherever it is in the body. Any treatment you take as a tablet or have through a drip (IV [intravenous] infusion) into a vein is systemic.

In cancer care, chemotherapy, hormone therapy, immunotherapy, and targeted therapies given by mouth or by injection are called ‘systemic’.

Cancers that have spread are generally treated with systemic therapies because they can reach the cancer cells wherever they are in the body.

How KRAS-Targeted Treatment Is Helping

Before treatments were developed, people with KRAS-positive advanced NSCLC didn’t do as well as those without a KRAS mutation in their tumors. But KRAS-targeted treatment may change that.

Clinical trials have looked at treating advanced NSCLC with the G12C mutation. More than 1 in 3 (33%) patients who participated in the trials had their cancer shrink or stop growing for a few months. These were early Phase I and II trials. Research is ongoing in later-phase randomized trials.

Sadly, we know that the treatment currently available will not permanently stop advanced lung cancer from growing. In these trials, the treatment controlled advanced disease for approximately 6 to 7 months.

Important: Statistics apply to the overall population of trial participants and can’t predict what will happen in your case. They can only be a general guide to what may help you. It’s best to discuss this with your own specialist, who has all the test results that apply to you.

Trials are now looking into whether KRAS-targeted therapy may help when combined with other types of treatment, such as chemotherapy or immunotherapy.

So far, we only know that KRAS-targeting treatments can help with advanced disease. But now researchers are starting to look into whether the treatment could help people with early-stage lung cancer.

KRAS Vaccines and Genetic Engineering

Researchers are currently looking into creating vaccines that target KRAS mutations in people with advanced lung cancer and at modifying a patient’s own immune system cells to help them target cancer cells. Both these types of treatment are still in the early stages of research.

Information based on Fast Facts for Patients: Non-small Cell Lung Cancer with KRAS Mutation (Karger, 2023).