Non-small-cell lung cancer (NSCLC) treatment has changed a lot in recent years. Your doctor may check your lung cancer cells for certain DNA changes. If no DNA changes are found, it is called nonmutated NSCLC.
Many people have nonmutated NSCLC and you may wonder which of the newest treatments can help because it can be harder to treat. That's because many newer medicines target specific DNA changes in cancer cells. Still, some new medicines can work for people with nonmutated NSCLC.
Today's treatments can block extra proteins made in tumor cells to kill them. They're more precise and personalized. "These treatments can be very effective, leading to a [long-lasting] treatment response," says Lee Hong, MD, PhD, assistant clinical professor in the Department of Medical Oncology and Therapeutics Research at City of Hope in Irvine, California.
This means there's more hope if you're living with NSCLC. These breakthrough treatments have greatly improved the outlook for lung cancer, "even for people with advanced disease like stage IV," says Hong, who is also a thoracic oncologist at City of Hope Orange County Cancer Specialty Hospital.
Older chemotherapy drugs are often added to newer medicines to make personalized care plans. This guide covers the latest lung cancer treatment options.
Ways to Treat NSCLC
Your treatment plan can depend on many things, such as your:
- Cancer stage (tumor size and location)
- Other health conditions
- Tumor proteins (biomarkers)
- Tumor mutations
Your oncologist can combine therapies to treat your lung cancer. Some treatments may treat your whole body such as chemotherapy or use surgery to take a part of your lung. Sometimes, a section or whole lung may be removed, depending on the location of your lung tumor.
Other treatments include radiation, radiofrequency ablation (RFA), cryoblation, and more. Your doctor can combine these treatments with immunotherapy.
Current Therapies for NSCLC
Immunotherapy forms the backbone of NSCLC treatment today. "It helps the immune system become activated to recognize and kill the cancer cells," says Hong. They can deliver medicine or immune cells directly to your cancer cells. And for lung cancer, that most often involves checkpoint inhibitors.
Even though your immune system is designed to kill cancer cells, sometimes it can't find them. "Cancer cells fool the immune system," says Ramaswamy Govindan, MD, Anheuser-Busch Endowed Chair in Medical Oncology at the Alvin J. Siteman Cancer Center in St. Louis. "They play hide and seek."
Checkpoint protein blockers
Normally, your healthy tissues use checkpoint proteins to stop your immune system from killing them. But tumors make more checkpoint proteins to hide, such as:
- Programmed cell death protein-1 (PD-1): Found on specific immune cells (T cells)
- Programmed death-ligand 1 (PD-L1) protein: Found on T cells and some tumor cells
- Cytotoxic T-lymphocyte-associated protein 4 (CTLA-4): Also found on T cells
Doctors use immune checkpoint inhibitors to block and release the brakes at these checkpoints. This type of immunotherapy takes cancer cells out of hiding so your immune system can find and destroy lung cancer.
Treatments for low checkpoint protein (PD-L1)
If your tumor has PD-L1 protein levels that are lower than 1% and no gene mutations, treatment depends on the type of NSCLC:
Nonsquamous NSCLC. Chemo medicines such as pemetrexed (Alimta) and carboplatin combined with PD-1 inhibitor pembrolizumab (Keytruda) may help. Another option is atezolizumab (Tecentriq or Tecentriq Hybreza) with either carboplatin or paclitaxel, and bevacizumab (Avastin) — a targeted therapy to shrink the tumor's blood supply.
Advanced squamous NSCLC. Pembrolizumab combined with chemo like carboplatin and paclitaxel (Taxol) may be a good option.
Another type of advanced NSCLC. You may receive pembrolizumab with pemetrexed and a platinum-based chemo drug.
But if your tumor PD-L1 levels are a little higher than 1%, your doctor may suggest:
- Nivolumab (Opdivo and Opdivo Qvantig) to block PD-1 and ipilimumab (Yervoy) to block CTLA-4, with or without chemo
- Chemo plus tremelimumab (Imjudo), another CTLA-4 inhibitor, and the PD-L1 inhibitor called durvalumab (Imfinzi)
Treatments for high checkpoint protein (PD-L1)
If your tumor PD-L1 levels are higher than 50%, your doctor may suggest pembrolizumab or cemiplimab (Libtayo). In some cases, atezolizumab (Tecentriq), a PD-L1 inhibitor, may also help with or without chemotherapy.
Checkpoint inhibitors don't help everyone because some tumors don't respond to treatment, or do but come back again. Researchers like Hong study how to use biomarkers to predict which treatments might work better for certain tumors and prevent return.
Cutting Edge NSCLC Treatments
Rcently, many NSCLC medicines target different proteins and DNA changes in lung cancer cells. "The most exciting breakthroughs are understanding the biology of how these cancers become resistant to current therapies," says Hong.
Sometimes, your treatment can stop working --- treatment resistance. After treatment, your lung cancer cells may develop new DNA changes that can show up on testing. If this happens, some targeted medicines may work better.
Researchers hope to develop new targeted therapies to overcome this problem.
Targeted kinase inhibitors
Here are some medicines that target cancer cells by blocking certain proteins and gene changes:
- Taletrectinib (Ibtrozi) for ROS1-positive NSCLC
- Sevabertinib (Hyrnuo) for HER2-mutated NSCLC
- Sunvozertinib (Zegfrovy) for EGFR-mutated NSCLC
- Zongertinib (Hernexeos) for HER2-mutated NSCLC
- Zidesamtinib (Jideytro) for ROS1-positive NSCLC
Antibody-drug conjugates (ADCs)
These medicines combine chemotherapy with targeted delivery to quickly find your cancer cells and kill them. "They're almost like a smart bomb," Govindan says. The two newest ADCs approved include:
- Datopotamab deruxtecan (Datroway): An ADC for EGFR-mutated NSCLC
- Telisotuzumab vedotin (Emrelis): An ADC for NSCLC that makes too much c-MET protein
Bispecific antibodies
This medicine is a Y-shaped antibody that can grab two different proteins and bring them closer together. One "arm" grabs the cancer cell, while the other grabs your immune cell. By pulling them together, your immune system can quickly find and kill lung cancer cells. Here are some bispecific antibody treatments:
Clinical Trials on the Horizon for NSCLC
"Over the last 10 to 15 years, we have seen a striking number of new drugs that potentially have changed the face of this cancer," says Govindan. Some new treatments have even cured advanced cancers that were once thought to be incurable. Here are a few treatments being studied in clinical trials.
New checkpoint inhibitors
LAG-3 inhibitors. Lung cancer cells make too much LAG-3 to spread faster. Researchers are studying whether LAG-3 inhibitors alone or with a PD-1 inhibitor might help you live longer.
TIGIT inhibitors. Tiragolumab is a TIGIT inhibitor that shows promise on its own as well as in combination with a PD-1 or PD-L1 inhibitor.
TIM-3 inhibitors. Tumors make more of the TIM-3 protein to grow and spread faster. Studies are checking if blocking TIM-3 — either alone or with a PD-1/PD-L1 inhibitor — may help.
CD-47 inhibitors. CD-47 acts like a “don't eat me” signal that about 30% of NSCLC tumors use to hide. Studies are checking if CD-47 inhibitors can help your immune system find and kill treatment-resistant lung cancer.
Bispecific antibodies in clinical trial
Ivonescimab. A PD-1 and PD-L1 inhibitor as well as a vascular endothelial growth factor (VEGF) inhibitor. Studies are finding out if it helps your immune system attack lung cancer cells and shrink the blood vessels that feed your tumor.
Cadonilimab. It's a bispecific antibody that targets PD-1 and CTLA-4. Trials are going on to see if blocking both checkpoint proteins can help with advanced NSCLC.
Viral immunotherapy
Viral immunotherapy can change viruses in a lab so only your cancer cells, not healthy ones, are infected. After the cancer cells die, they release proteins that "wake up" your immune system to better find and kill cancer cells.
CAN-2409. This uses the adenovirus that causes colds to deliver the herpes simplex virus thymidine kinase (HSV-tk) gene into lung cancer cells. Now the lung cancer cells contain the HSV-tk gene, which makes the medicine toxic. Then, you can take the antiviral medicine called valacyclovir to kill your lung cancer.
Studies show that if checkpoint inhibitors aren't working, CAN-2409 may help just over a third of people with late-stage NSCLC live at least two more years.
Cancer vaccines
Cancer vaccines can "train" your immune system to find and kill cancer cells. "We take a piece of the tumor tissue, develop the vaccine based on the types of unique proteins that are in each patient's cancer, and then inject the vaccine," says Hong.
The NSCLC vaccine studies are underway, but slow. It can take many years to know if it works. With advanced cancer, the vaccines may need to be used with other treatments to work.
CAR-T cell therapy
CAR-T changes your immune cells in a lab to help them better fight cancer. It works very well against blood cancers, but not for solid tumors such as lung cancer.
That's because lung cancer is made up of many types of cells and tissues. The therapy can also cause serious side effects. "CAR-T cell therapy is still very much in the early stages of development, but it's an active area of research," Hong says.
Future Directions
The search for lung cancer medicines continues. The goal is to develop new treatments that only kill cancer cells, not healthy ones. Research has made new treatments and people make cancer research possible. Ask your oncologist whether you're eligible to join a clinical trial for NSCLC or check out the ClinicalTrials.gov website.
"The magic bullet hits the cancer, but it spares normal organs that are not affected by cancer," says Hong. "Chemotherapy was our first foray into that, but with more technological advances, we're getting even better at delivering therapy to your cancer."
