Clinical practice review of systemic treatment in large cell neuroendocrine carcinoma

Large cell neuroendocrine carcinomas (LCNECs) of the lung make up only 3.1% of all primary lung cancers, making them highly uncommon when compared to other primary lung cancers. For patients with stage I, II, or III LCNEC of the lung, surgery is the preferred first-line treatment. However, due to high recurrence rates, surgery alone is often insufficient to fully treat patients' disease. Adjuvant therapy utilizing platinum-based chemotherapy has been shown to improve survival in patients with LCNEC. For patients with unresectable or metastatic disease, chemotherapy is generally the first line of treatment, often a combination of either cisplatin or carboplatin with etoposide or irinotecan. However, the low response and survival rates leave room for advancement. There are several other treatments currently being investigated, which will be discussed in this review. Immunotherapy, which is often used to treat small-cell lung cancers, is yet to officially be defined as a treatment for LCNEC of the lung. Additionally, bispecific T-cell engagers (BiTEs) are also being explored in current trials as potential treatments and show promise as a potential treatment. Novel therapies such as chimeric antigen receptor T (CAR-T) cells and oncolytic viruses are being investigated. These studies are critical as patients with large cell neuroendocrine cancers tend to demonstrate poor 5-year survival rates at 35.5%, and even worse rates of 5-year recurrence-free survival at 27.4%. Given the aggressive nature and poor prognosis, further research into this disease is critical. We aim to review and summarize the current literature on systemic treatment in LCNEC.