It’s often hard to find lung cancer until it spreads to other parts of your body. Your doctor will call this metastasized, and they may refer to your type of cancer as metastatic. Most often the disease travels to lymph nodes near or far from the lungs, the adrenal gland, the brain, or the other lung.
This advanced form of lung cancer can be harder to treat. But combining treatments can help. When doctors use two or more methods to treat cancer, they call it combination therapy.
They do this for a few reasons:
- One treatment alone may not make the cancer shrink or go away.
- Adding one makes the original work better.
- Certain treatments work better at different stages of your treatment.
The combination therapy that your doctor might recommend for you partly depends on which type of lung cancer you have. There are two main types:
- Non-small-cell lung cancer (NSCLC). Most cases of lung cancer – up to 85% – are this type.
- Small-cell lung cancer (SCLC). This type is much less common. It tends to grow and spread faster than NSCLC. Usually it has spread by the time your doctor diagnoses it.
Here are the kinds of combination therapy that doctors use for each.
Combination Therapy for Metastatic NSCLC
If you have this type of 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 others, either at the same time or later, to try to get the best results.
Doctors are testing ways to pair new medicines with existing treatments for metastatic lung cancer, like chemotherapy and radiation, so that more people will benefit from them.
Newer medicines that work on your immune system (immunotherapy) or target substances found on or in cancer cells (targeted therapy) have emerged in the last few years. Often they’re a game changer for people with metastatic non-small-cell lung cancer.
Your immune system works 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 and attack them.
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 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.
Doctors can combine many of the treatments for metastatic NSCLC in a number of ways.
Targeted therapies. Depending on the drug, these treatments can be used alone or with chemotherapy to treat lung cancer.
- Afatinib (Gilotrif), amivantamab-vmjw (Rybrevant), dacomitinib (Vizimpro), erlotinib (Tarceva), gefitinib (Iressa), mobocertinib (Exkivity), necitumumab (Portrazza), and osimertinib (Tagrisso) all target a lung cancer cell protein called EGFR. They work if you need treatment in addition to chemotherapy.
- Bevacizumab (Avastin) and ramucirumab (Cyramza) are used with chemotherapy. They stop tumor growth by cutting off the “food” -- nutrients, blood supply, and oxygen -- needed for them to grow.
- Alectinib (Alecensa), brigatinib (Alunbrig), ceritinib (Zykadia), crizotinib (Xalkori), and lorlatinib (Lorbrena) are used for cancers with a gene rearrangement called ALK.
- Adagrasib (Krazati) and sotorasib (Lumakras) target the genetic mutation called KRAS G12C.
Many new drugs target specific gene changes, and some of them can be used alone once tests help your doctor identify the mutation.
Checkpoint inhibitors. These are medicines that restart your immune system so it can recognize and fight cancer. This helps shrink or slow the growth of tumors.
The following medicines are FDA-approved immunotherapy drugs to treat certain types of non-small-cell lung cancer:
- Cemiplimab (Libtayo), nivolumab (Opdivo), and pembrolizumab (Keytruda) 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) and durvalumab (Imfinzi) target PD-L1. These drugs are used if your cancer cells have certain genetic markers.
You take these drugs intravenously (through the veins) every 2 or 6 weeks depending on the medicine and the dose.
Atezolizumab, ipilimumab (Yervoy), nivolumab, and pembrolizumab can be used along with chemotherapy.
Immunotherapy with chemotherapy. Chemo is a standard treatment for advanced lung cancer. Different types of it 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, doctors use radiation mainly 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.
But they need to do more research to figure out what types of tumors will respond best to this treatment as well as what doses to give and how often.
Immunotherapy drugs together. Early results hint that combining two checkpoint inhibitors might work better than using just one.
Doctors are also using immunotherapy drugs for lung cancer that have also been approved to treat other types of cancer, like melanoma. One of these drugs, ipilimumab (Yervoy), is approved in combination with nivolumab (Opdivo).
Surgery plus other treatments. It’s not common to have metastatic non-small-cell lung cancer that’s limited in your lungs and has only spread to one other place in your body, like the brain. But if you have this, your doctor may be able to treat it, and possibly cure it, by:
- Doing surgery and radiation therapy (or either alone) where the cancer spread
- Then treating the cancer in your lung with surgery, chemo, or radiation, or using some of these together. This part of the treatment depends on the size and extent of your lung tumor and whether the cancer has spread to nearby nodes.
Combination Therapy for Metastatic SCLC
Small-cell lung cancer has often spread by the time a doctor spots it. If you have metastatic SCLC, your doctor might also call it extensive-stage SCLC.
It’s possible for treatments to boost your quality of life and help you live longer, but this type of cancer usually comes back.
If your health is fairly good, your doctor might give you a combination of chemotherapy meds, possibly along with immunotherapy, as a first treatment. It might shrink your cancer, ease your symptoms, and help lengthen your life.
The chemo combination doctors use most commonly is etoposide plus either cisplatin or carboplatin. The immunotherapy drugs atezolizumab (Tecentriq) or durvalumab (Imfinzi) can be given along with etoposide and either cisplatin or carboplatin as a first treatment.
If the treatment works, your doctor might recommend radiation to your chest to help you live longer. They might also suggest radiation to your brain to help lower the chances of the cancer spreading there.
If you’re in poor health overall, the side effects from standard doses of chemo might be too much for you. In that case, your doctor might give you lower doses of chemo. Or they might offer you treatments that focus on easing your pain and other symptoms while keeping you as comfortable as possible.
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.
