Immunotherapy and Targeted Therapy for Lung Cancer

• Small molecules: These can enter cells effortlessly, so they are utilized for intracellular targeting.
• Monoclonal antibodies: These are proteins synthesized in the lab with varying techniques. Some are made to mark cancer cells to be recognized by the immune system and destroyed, others can stop cancer cells from growing or cause them to self-destruct, and then some are loaded with toxic drugs to directly project them into cancer cells. This last form is called an antibody drug conjugate and there have been many new exciting advancements with this type f therapy.

"Using a patient's own immune cells is a very complex way to treat a cancer," says Dr. Rosenberg. His team has developed methods for genetically modifying a patient's own immune cells "to recognize the cancer in a new way" and to kill it.

Types of immunotherapy for lung cancer

One type of immunotherapy  for lung cancer, a form of immunotherapy called ipilimumab, was approved by the FDA in 2011. It works by blocking a protein called CTLA-4 on immune cells and preventing them from turning off T cells that attack tumors. It’s currently used as an additional treatment in combination with chemotherapy for patients whose tumors have not responded to other drugs.

Another immunotherapy for lung cancer is nivolumab (Opdivo), which blocks PD-1 receptors on immune cells and prevents them from stopping T cells from attacking tumors. It was approved by the FDA in 2014 and has since been shown to improve survival rates when used with chemotherapy in patients with advanced lung cancer who had previously been treated with chemotherapy or radiation therapy.

Additionally, there’s pembrolizumab (Keytruda), which binds to PD-1 receptors on immune cells and stops cancer.

Keytruda cancer treatment

Keytruda cancer treatment is one of the most widely used forms of immunotherapy for lung cancer and has been approved by the FDA since 2016. It works by targeting a protein called PD-1 on tumor cells so that they can be destroyed by your immune system. In addition to its treatment effectiveness for lung cancer, Keytruda has also shown promise in fighting other forms of cancer, including melanoma and bladder cancer. When used alone or in combination with chemotherapy drugs (such as cisplatin), Keytruda has been shown to improve survival rates by an average of six months over standard chemotherapy.

Side effects of targeted and immune-therapy

Targeted therapy and immunotherapy can have fewer side effects since they only target cancer cells as opposed to chemotherapy or radiation therapy, damaging both cancer and healthy cells. Nevertheless, every patient will experience side effects differently.

Furthermore, side effects are remarkably diverse and will vary depending on:

• Type of targeted drug or immunotherapy
• Dose of the drug
• If there are any treatment combinations
• Overall health
• Method of administration

Here's a list of some of the most common side effects of targeted therapies that you can experience during or after treatment:

• Fatigue or tiredness
• Low immune cells count (white blood cells)
• Breathing difficulties
• Coughing
• Diarrhea
• Constipation
• Change in taste
• Loss of appetite
• Flu-like symptoms
• Nausea
• Weight gain
• Skin reactions (ex. rashes or itching)
• Eye problems (ex., light sensitivity, dryness, redness, or impaired vision)

However, be sure to always consult your doctor about what to expect when undergoing targeted treatment for your cancer because some targeted therapies cause other serious side effects.

Targeted therapy drugs for lung cancer

At this time, researchers have successfully produced many non-small cell lung cancer targeted drugs that are specific for changes in genes and proteins found within cancer cells. These include the following targeted therapies:

• Targeting blood vessel growth (also known as the angiogenesis process)

Because tumors need blood vessels for nutrition to grow, angiogenesis inhibitors directly target them to stop their growth. Drugs that fall under this category are generally combined with chemotherapy to treat late-stage non-small cell non-squamous lung cancer. They can be accompanied by some serious adverse events like blood clotting, intestinal perforation (holes in the intestines), severe bleeding, and heart problems. Available angiogenesis inhibitor drugs are Bevacizumab (Avastin) or Ramucirumab (Cyramza).

• Targeting KRAS gene mutations

Gene mutations in KRAS can be one of the risk factors for developing non-small cell lung cancer. Thus, KRAS inhibitors are used to stop cancer cells with this mutation from growing. They can be accompanied by some serious side effects, including liver damage and lung scarring. Available KRAS inhibitor drugs are Sotorasib (Lumakras).

• Targeting EGFR mutations

Under normal circumstances, EGFR is a protein that helps cells grow, but when it turns into a cancer cell, it needs to be stopped. Available EGFR inhibitors include Erlotinib (Tarceva), Afatinib (Gilotrif), Gefitinib (Iressa), Osimertinib (Tagrisso), and Dacomitinib (Vizimpro). Some of them may be used to treat the initial stages of the disease, while others treat the late stages of the disease. The more serious side effects caused by these medications are infections, allergic reactions, eye problems, serious lung disease, blood deficiencies, and damage to the heart muscle.

EGFR inhibitor treatments usually don't work forever as patients tend to develop other mutations. So, it's important to follow up with your doctor to change the plan of treatment when this happens.

• Targeting ALK gene mutations

Five percent of non-small cell lung cancer (NSCLC) patients are caused by ALK gene mutations. Some of these drugs include Crizotinib (Xalkori), Ceritinib (Zykadia), Alectinib (Alecensa), Brigatinib (Alunbrig), and Lorlatinib (Lorbrena). Other serious side effects include nerve damage, liver damage, and heart rhythm problems.

• Targeting ROS1 gene mutations

ROS1 inhibitors can reduce the size of tumors. These ROS1 inhibitors drugs are Crizotinib (Xalkori), Ceritinib (Zykadia), Lorlatinib (Lorbrena), and Entrectinib (Rozlytrek). Some of the more serious side effects include lung swelling, liver damage, and heart problems.

• Targeting BRAF gene mutations

Some of the drugs that target BRAF gene changes include Dabrafenib (Tafinlar). Among some of the serious side effects are increased blood sugar, severe allergic reaction, and lung problems.

RET inhibitors, MET inhibitors, and NTRK inhibitors are also available drugs that target gene mutations causing lung cancer. Similarly, they can bring about serious side effects. Thus, it's imperative to discuss with your healthcare provider all the information about the drugs before taking them.

Dr. Ronald Natale, a Medical Oncologist with 48 years of experience in the field, shared his thoughts with SurvivorNet by saying, "Erlotinib (Tarceva) and gefitinib (Iressa) were among the first targeted drugs approved to treat lung cancer. These and other similar drugs given as pills target epidermal growth factor receptor (EGFR), a protein that, when overreactive, makes cancer cells grow and divide. These mutations are more common in people with lung cancer who are female or who have never smoked."

Targeted and immunotherapy VS. Chemotherapy

There are many differences between chemotherapy, immunotherapy, and targeted therapies. Oftentimes, targeted therapy and immunotherapy can be more effective compared with traditional cytotoxic chemotherapies Some of the main differences between these three therapies include:

• High accuracy (they target only cancer cells without damaging neighboring healthy cells.)
• Reduced side effects when compared with other treatments.
• Appropriate for elder or weak patients who can't tolerate chemotherapy.
• Very effective.

If you have lung cancer and get targeted therapy, you’ll still need to be regularly monitored for:

• Signs that cancer may be growing again.
• Check cancer's response to the drug.
• Be monitored for any symptoms or side effects from therapy

Nonetheless, if your lung cancer isn’t responding to the targeted therapy, you must tell your doctor right away so they can switch you over to another type of targeted therapy or chemotherapy.

As Dr. Natale puts it, "These drugs have had success in prolonging the time that cancer does not worsen, both alone and in combination with chemotherapy. If cancer does not respond to inhibitor therapy, a wide variety of options exist and include using radiation, continuing the current therapy, adding other targeted treatments, or changing to chemotherapy."

The Bottom Line

Lung cancer can be a scary diagnosis, and it’s especially scary if you’re in the late stages. But with the arrival of these targeted new treatments there is renewed hope for further advancements and improvements in outcomes.

Next to lung cancer, targeted and immuno therapy has been effective in several types of other cancers, including breast cancer, colon cancer, head and neck squamous cell carcinoma (HNSCC), melanoma, prostate cancer, and renal cell carcinoma.

It’s important to note that the drug isn’t meant to replace chemotherapy or radiotherapy; it’s just another option for treating lung cancer that can work alongside theose other methods. We’ll know more about how well this treatment works once further studies are completed, but for now, it looks promising!

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