Immunotherapy
For Lung Cancer

How is Immunotherapy for Lung Cancer Changing the Outlook for Patients?

Reviewed by:

Matthew Hellmann, MD
Memorial Sloan Kettering Cancer Center

Immunotherapy for lung cancer, alone or in combination with conventional treatments, can significantly improve outcomes for patients fighting lung cancer.

As the most common cancer worldwide, lung cancer impacts approximately 2.1 million people—and causes an estimated 1.7 million deaths—each year and is the leading cause of cancer-related deaths for both men and women. In the United States alone, there were an estimated 240,000 new lung cancer cases along with 130,000 deaths in 2023. Lung cancer claims more lives every year than do cancers of the breast, prostate, and colon combined.

Lung cancer is subdivided into two major types: 

• Small cell lung cancer (SCLC) comprises approximately 10-15% of all known lung cancer cases.
• Non-small cell lung cancer (NSCLC) comprises approximately 85-90% of all known lung cancers cases.
  • Adenocarcinoma arises from cells in the lung that secrete substances such as mucus (40% of lung cancers).
  • Squamous cell (epidermoid) carcinoma arises from the flat squamous cells that line the inside of the airways of the lung (25-30% of lung cancers). 
  • Large cell (undifferentiated) carcinoma typically arises from the epithelial cells that line the outer regions of the lung (10-15% of lung cancers).
• Mesothelioma arises from a thin layer of tissue that covers many organs and most commonly occurs around the lungs.

When most lung cancer patients become symptomatic and are diagnosed, the disease has already advanced to late stage (at stage 3b/4 or higher). At these stages, surgery, chemotherapy, and radiation are only minimally effective. New treatments are needed for patients facing an advanced lung cancer diagnosis. Fortunately, immune-based cancer treatments are helping to improve chances of living longer for patients with lung cancer.

Lung Cancer Treatment Options

Until recently, conventional treatment options for lung cancer included surgery, chemotherapy, and radiation. Since the majority of lung cancer patients are diagnosed with advanced disease (stage 3b/4), these treatments are unlikely to result in complete cures, though they may significantly improve survival and provide symptom relief.

In 2015, the U.S. FDA approved the first immunotherapy to treat a subset of lung cancer patients. Immunotherapy is class of treatments that helps a person’s own immune system eliminate or control cancer. Recent clinical studies treating patients with immunotherapy, either alone or in combination with other treatments, have demonstrated significant patient improvement, resulting in FDA approval of several other immunotherapy options for more lung cancer patients, including approvals to treat patients with immunotherapy as a first-line therapy instead of conventional treatments.

Targeted Antibodies

• Amivantamab (Rybrevant™): a bispecific antibody that targets EGFR and MET receptors on tumor cells; approved for subsets of patients with non–small cell lung cancer (NSCLC)
• Bevacizumab (Avastin®): a monoclonal antibody that targets the VEGF/VEGFR pathway and inhibits tumor blood vessel growth; approved for subsets of patients with advanced non-small cell lung cancer (NSCLC), including as a first-line therapy
• Necitumumab (Portrazza®): a monoclonal antibody that targets the EGFR pathway; approved for subsets of patients with advanced non-small cell lung cancer (NSCLC), including as a first-line therapy
• Ramucirumab (Cyramza®): a monoclonal antibody that targets the VEGF/VEGFR2 pathway and inhibits tumor blood vessel growth; approved for subsets of patients with non-small cell lung cancer (NSCLC), including as a first-line therapy
• Trastuzumab deruxtecan (Enhertu®): an antibody-drug conjugate that targets the HER2 pathway and delivers toxic drugs to tumors; approved for subsets of patients with advanced lung cancer

Immunomodulators

• Atezolizumab (Tecentriq®): a checkpoint inhibitor that targets the PD-1/PD-L1 pathway; approved for patients with advanced non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC), including as a first-line therapy in combination with chemotherapy.
• Cemiplimab (Libtayo®): a checkpoint inhibitor that targets the PD-1/PD-L1 pathway; approved for a subset of patients with advanced non–small cell lung cancer (NSCLC) 
• Dostarlimab (Jemperli): a checkpoint inhibitor that targets the PD-1/PD-L1 pathway; approved for subsets of patients with advanced lung cancer that has DNA mismatch repair deficiency (dMMR)
• Durvalumab (Imfinzi®): a checkpoint inhibitor that targets the PD-1/PD-L1 pathway; approved for subsets of patients with lung cancer, including in combination with tremelimumab
• Ipilimumab (Yervoy®): a checkpoint inhibitor that targets the CTLA-4 pathway; approved, in combination with nivolumab, as a first-line treatment, both with or without chemotherapy, for patients with advanced non-small cell lung cancer (NSCLC) and mesothelioma
• Nivolumab (Opdivo®): a checkpoint inhibitor that targets the PD-1/PD-L1 pathway; approved for patients with advanced non-small cell lung cancer (NSCLC) and mesothelioma in combination with ipilimumab, with or without chemotherapy; also approved for NSCLC in the neoadjuvant (pre-surgical) setting in combination with chemotherapy
• Pembrolizumab (Keytruda®): a checkpoint inhibitor that targets the PD-1/PD-L1 pathway; approved for patients with non-small cell lung cancer (NSCLC), including as a first-line therapy, an adjuvant (post-surgery) therapy, or in combination with chemotherapy
• Tremelimumab (Imjudo®): a checkpoint inhibitor that targets the CTLA-4 pathway; approved in combination with durvalumab and chemotherapy for subsets of patients with metastatic lung cancer

These checkpoint immunotherapy approvals were landmark events for the treatment of lung cancer. With these immunotherapies, many advanced-stage lung cancer patients are starting to see long-lasting remissions and longer survival rates. Several immunotherapy agents are currently being tested in lung cancer clinical trials.

CRI’s Impact in Lung Cancer

Since its founding, the Cancer Research Institute (CRI) has dedicated numerous grants and fellowships to the research of immunotherapy for lung cancer. We continue to fund the science of immune-based therapies for lung cancer, supporting the best scientists working to advance the field of this promising treatment.

CRI-funded discoveries and breakthroughs, along with ongoing studies, include: 

• The benefits of anti-PD-1 checkpoint immunotherapy prior to surgery in patients with advanced lung cancer, highlighted in a recent study led by members of the CRI-SU2C Dream Team
• The connection between the number of genetic mutations of lung tumors and patient responses to treatment with anti-PD-1 checkpoint immunotherapy, discovered by a team led by Naiyer Rizvi, MD, of Columbia University Medical Center
• A “human breathing lung-on-a-chip” device, developed by Technology Impact Award recipient Dan Huh, PhD, of the University of Pennsylvania, that is capable of mimicking normal lung biology and allowing for in-depth characterization of how various factors affect disease
• A vaccine targeting the NY-ESO-1 antigen, developed through the CRI/Ludwig Cancer Antigen Discovery Collaborative, that led to responses in lung cancer patients
• A clinical study, funded by the CRI Clinical Accelerator, that uses blood tests to detect circulating tumor DNA (ctDNA) in NSCLC patients on treatment with pembrolizumab to better understand patient response and treatment regimen

See what lung cancer-specific research we’re currently funding. With your help, we can fund more research and revolutionize the way lung cancer is treated, forever—helping more people and saving more lives.