Focus on current therapy management of NSCLC

Non-small cell lung cancer is a common cancer with generally poor prognosis. Scientific advances have led to new forms of therapy increasing the chance of survival. In particular, the development of immunotherapy with checkpoint inhibitors has revolutionized the options for NSCLC treatment.

Bronchus carcinoma (NSCLC) is one of the most common cancers worldwide, ranking 2nd in the incidence of malignancies in men and 3rd in women. Depending on the stage, locally effective therapeutic procedures such as surgery and radiotherapy, or systemically effective treatments such as chemotherapy, targeted drugs or immunotherapeutics are used. The decision regarding the optimal individual treatment regimen depends on the extent of lymph node involvement and other factors such as age, general condition and comorbidities. Therefore, a precise assessment of the disease situation in an interdisciplinary consultation is essential.

In advanced NSCLC, there were limited further treatment options for a long time after a platinum doublet. This only changed with the introduction of immunotherapy. Tumor cells evade the body’s own immune defenses. The T cell expresses on itCTLA-4 and PD-1. These inhibitory molecules prevent an exuberant immune response and are also called immune checkpoints. However, in the context of tumor diseases, they prevent an adequate effector response. This is where immunotherapy comes in, using antibodies against CTLA-4, PD-1 or their ligands to activate the immune system. The eradication of tumor cells by the patient’s own immune system is the result. NSCLC is a suitable candidate for treatment with checkpoint inhibitors due to its high mutation rate.

Effective side effect management

Compared to cytotoxic chemotherapy, immunotherapy is usually better tolerated. However, in addition to fatigue and loss of appetite, new immune-mediated side effects are emerging. The basis for this is very likely a non-specific activation of the immune system, which leads to autoimmune destruction of tissue. However, the exact pathophysiological mechanisms are not yet clear. In mild cases, a break in treatment or close clinical and laboratory monitoring while continuing therapy is often sufficient. Primarily, corticosteroids are used to treat the immune-mediated side effects. In the meantime, these new complaints can usually be managed well and are also taken into account accordingly in the current guidelines.

Prolonged overall survival

Immunotherapy is used alone or in combination with chemotherapy for tumors with stage IIIB/IIIC or IV disease. In the metastatic setting, checkpoint inhibitors were initially used in the second-line setting, where they showed prolonged overall survival compared with docetaxel treatment. In therapy-naive patients with PD-L1 expression ≥50% on tumor cells, the PD-1 inhibitor pembrolizumab can now be used as first-line palliative therapy. In contrast to platinum-containing chemotherapy, this showed a benefit in terms of progression-free survival and overall survival. In patients with PD-L1 expression <50%, immunotherapy is used in combination with cytotoxic chemotherapy.