In recent years, the treatment of advanced NSCLC has radically evolved with the introduction in clinical practice of targeted therapies against specific molecular alterations and immune checkpoint inhibitors (ICIs). About two-thirds of NSCLCs are detected at an advanced or metastatic disease stage. Histologically, non-small-cell lung cancer (NSCLC) is the most frequent lung cancer subtype, accounting for approximately 85% of diagnoses, and comprises the most common histotypes like adenocarcinoma and squamous cell carcinoma. Lung cancer is one of the most common human cancers and the leading cause of cancer-related mortality worldwide, according to data from the Global Cancer Observatory (, accessed on 10 November 2022). In addition, the two-year immunotherapy scheme in patients who benefit from first-line or subsequent treatment lines are examined, and the need for biomarkers that can predict outcomes during and after immunotherapy cessation in patients affected by NSCLC are discussed. Data regarding the duration of immunotherapy in the most impacting clinical trials were collected, along with data regarding the impact of toxicities, side effects, and costs for healthcare providers. We performed a narrative review to discuss all the aspects related to the optimal duration of immunotherapy in long survivors with NSCLC. Therefore, the optimal duration of immunotherapy in long survivors needs to be established to avoid overtreatment, side effects, and high costs and at the same time, protect them from potential disease relapse or progression. Currently, it is estimated that long-term survival can be achieved in more than 15% of NSCLC patients treated with immunotherapy. The advent of immunotherapy for the treatment of NSCLC has significantly improved overall and progression-free survival, as well as the patient’s quality of life in comparison to traditional chemotherapy. Novel therapeutic approaches, like targeted therapies against specific molecular alterations and immunotherapy, have revolutionized in the last decade the oncological outcomes in patients affected by non-small cell lung cancer (NSCLC). Lung cancer is one of the most common human malignancies and the leading cause of cancer-related death worldwide.
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