Combination Therapy for Metastatic Lung Cancer

Medically Reviewed by Melinda Ratini, DO, MS on December 07, 2021

It’s often hard to find lung cancer until it spreads to other parts of your body. (Your doctor will call this metastasized and may refer to your type of cancer as metastatic.) Most often it travels to lymph nodes near or away from the lungs, the adrenal gland, the brain, or the other lung.

This advanced form of the disease can also be harder to treat. But new medicines that work your immune system or target substances found on or in cancer cells have emerged in the last few years. Often they’re a game changer for people with one type of the disease, metastatic non-small-cell lung cancer (NSCLC).

Your immune systems work by attacking foreign or unhealthy cells. But cancer cells somehow trick it into not “seeing” them as an enemy. Immunotherapy helps your body recognize cancer cells as invaders and wage war against them.

One type of treatment, called targeted therapy, offers another way to strike cancer cells. Unlike traditional chemotherapy, which kills the cells, targeted therapy stops them from multiplying. But these drugs usually work only if there are certain changes, which your doctor will call mutations, in your genes.

So far, targeted therapy and immunotherapy don’t work for everyone. But doctors are testing ways to pair them with existing treatments for metastatic lung cancer, like chemotherapy and radiation, so that more people will benefit from them.

Combining Therapies

When doctors use two or more methods to treat cancer, they call it combination therapy. They do this for a couple of reasons:

  • One treatment alone may not make the cancer shrink or go away.
  • Adding one makes the original work better.
  • Certain therapies work better at different stages of your treatment.

If you have metastatic lung cancer, your doctor may start with something like chemotherapy, targeted therapy, or immunotherapy. They’ll choose the one they think is most likely to shrink your tumor or get rid of your cancer. If that drug doesn’t work like they expect, they might try one or more additional therapies, either at the same time or later to try to achieve the best results.

The FDA has approved several immunotherapy drugs for metastatic lung cancer for use before or after chemotherapy. Clinical trials are underway to see how well these drugs work with chemotherapy, radiation, and each other.

Targeted Therapies

These treatments can be used alone or with chemotherapy to treat lung cancer:

Checkpoint Inhibitors

The following are FDA-approved immunotherapy drugs to treat certain types of non-small-cell lung cancer. These so-called “checkpoint inhibitors” are medicines that restart your immune system so it can recognize and fight cancer. This helps shrink or slow the growth of tumors.

  • Nivolumab (Opdivo), cemiplimab (Libtayo), and pembrolizumab (Keytruda) both block a protein called PD-1 that normally keeps your immune system from attacking healthy cells and allows it to seek and destroy cancer cells. In order to get the drug, your tumor must have a substance called PD-1. The drug won’t work if it isn’t there.
  • Atezolizumab (Tecentriq), durvalumab (Imfinzi), and Ipilimumab (Yervoy) target PD-L1. These drugs are used if your cancer cells have certain genetic markers. You take all three of these drugs intravenously (through the veins) every 2 or 3 weeks.

You take these drugs intravenously (through the veins) every 2 or 3 weeks.

Immunotherapy With Chemotherapy

Chemotherapy is a standard treatment for advanced lung cancer. Different types of chemo can be used alone or with one another.

Some studies have shown using a mix of chemotherapy and immunotherapy as a first strike against NSCLC to be a good approach. It helps your immune system find and destroy cancer cells.

Immunotherapy With Radiation

Right now radiation is used mostly to ease metastatic lung cancer symptoms. Some doctors think that treating lung tumors with radiation first will spark an immune response and help immunotherapy drugs find and kill cancer cells. However, they need to do more research to figure out what types of tumors will respond best to this treatment and what doses to give and how often.

Immunotherapy Drugs Together

Early results hint that combining two checkpoint inhibitors might be more effective than using just one. Doctors are also testing immunotherapy drugs for lung cancer that have been approved to treat other types, like melanoma. One of these drugs, ipilimumab (Yervoy), is being tested in combination with nivolumab (Opdivo) to see if they work better together than chemotherapy alone.

When to Change Treatments

The goal for treatment is to limit tumor growth and stop the cancer’s spread. If chemotherapy can’t do this, your doctor may try other methods. They also may suggest that you enroll in a clinical trial where you’ll get access to drugs and therapies that are being tested. Sometimes, chemotherapy may do more harm than good. If this is the case, your doctor might turn to supportive care, which treats symptoms caused by your cancer.

Show Sources


Cancer Support Community: “Frankly Speaking about Cancer: Treatments for Advanced and Metastatic Lung Cancer.”

National Comprehensive Cancer Network: “NCCN Guidelines for Patients: Lung Cancer/Non-Small Cell Lung Cancer.”

National Cancer Institute: “Biological Therapies for Cancer,” “Lung Cancer Precision Medicine Trials: Adapting to Progress,” “More Immunotherapy Options Approved for Lung Cancer,” “SEER Training Modules: “Combination Treatments,” “Targeted Cancer Therapies.”

Translational Lung Cancer Research: “Immunotherapy in Lung Cancer.”

Memorial Sloan Kettering Cancer Center: “Combination Immunotherapy Shows New Promise for Lung Cancer.” “Non-small Cell Lung Cancer Treatment.”

Cancer Immunology Research: “Immune Checkpoint Inhibitors: Making Immunotherapy a Reality for the Treatment of Lung Cancer.”

American Cancer Society: “Immunotherapy for non-small cell lung cancer,” “Targeted therapy drugs for non-small cell lung cancer.”

Lung Cancer Alliance: “Immunotherapy for Lung Cancer: A Guide for the Patient.”

FDA: “Atezolizumab (TECENTRIQ).”

Therapeutic Advances in Medical Oncology: “Checkpoint inhibitors in lung cancer: latest developments and clinical potential.”

Cancer Treatment Reviews: “The abscopal effect of local radiotherapy: using immunology to make a rare event clinically relevant.” “When the First Treatment Doesn’t Work.”

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