Small cell lung cancer (SCLC) is an aggressive form of lung cancer, known for its rapid growth and early spread. For decades, treatment options offered limited improvements. However, immunotherapy has introduced a new approach, leveraging the body’s own defense mechanisms against cancer cells.
How Immunotherapy Works
The immune system naturally protects the body from foreign invaders and can also recognize and eliminate abnormal cells, including cancer cells. However, cancer cells often develop ways to evade this immune surveillance. One common evasion strategy involves “immune checkpoints,” which are proteins on immune cells that act like brakes, preventing the immune system from attacking healthy tissues.
Cancer cells can exploit these checkpoints to avoid detection and destruction by immune cells. Immunotherapy drugs, known as checkpoint inhibitors, work by blocking these proteins. For example, some drugs target PD-1 (Programmed Death-1) on immune cells or PD-L1 (Programmed Death-Ligand 1) on cancer cells. By blocking these interactions, checkpoint inhibitors release the brakes on the immune system, allowing immune cells, particularly T-cells, to recognize and attack the cancer cells more effectively.
Immunotherapy Medications for SCLC
Several immunotherapy medications are approved for use in small cell lung cancer, primarily immune checkpoint inhibitors. Atezolizumab (Tecentriq) and durvalumab (Imfinzi) are two examples, targeting the PD-L1 protein. These medications are typically administered intravenously.
Another type of immunotherapy, tarlatamab (Imdelltra), is a bispecific T-cell engager (BiTE). It connects T-cells directly to the DLL3 protein found on SCLC cells, facilitating the immune system’s attack.
When Immunotherapy is Used for SCLC
Immunotherapy is a standard treatment for extensive-stage small cell lung cancer (ES-SCLC), meaning the cancer has spread beyond one lung or one side of the chest. It is used as a first-line treatment with platinum-based chemotherapy (such as cisplatin or carboplatin and etoposide). This combination has shown improved overall survival compared to chemotherapy alone, extending survival by approximately 2-3 months.
After initial cycles of chemotherapy with immunotherapy, the immunotherapy agent may continue alone as maintenance therapy. This aims to sustain treatment benefits and prevent disease progression. For limited-stage SCLC, where the cancer is confined to one lung or one side of the chest, durvalumab has also shown promise in extending survival when given after chemotherapy and radiation.
Managing Immunotherapy Side Effects
Immunotherapy can cause unique side effects, distinct from traditional chemotherapy. These are known as immune-related adverse events (irAEs) and occur when the activated immune system mistakenly attacks healthy tissues. These side effects can affect nearly any organ system, including the skin, thyroid, lungs, and gastrointestinal tract.
Common irAEs include fatigue, skin rashes, itching, diarrhea, and inflammation of the lungs (pneumonitis) or colon (colitis). Endocrine issues, such as thyroid dysfunction (hypothyroidism or hyperthyroidism), can also occur. Patients should report any new or worsening symptoms to their healthcare team promptly, as early recognition and management are important. Management often involves corticosteroids to suppress the immune response; other immunosuppressive medications may also be needed.