Second-Line Chemotherapy and Beyond for Non–Small Cell Lung Cancer

The landscape for the second- and third-line treatment of advanced non–small cell lung cancer has changed dramatically over the last two decades. Immunotherapeutic agents have become a preferred choice following progression on platinum-based first-line chemotherapy. However, there remains a role for cytotoxic chemotherapy and pemetrexed and docetaxel (with or without ramucirumab) are approved for single-agent use in the second-line setting. With the discovery of new genetic alterations and the development of novel targeted drugs, the treatment of advanced non–small cell lung cancer following progression on first-line therapy continues to become more complicated as new treatment algorithms evolve.

Key points

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Docetaxel, pemetrexed, and erlotinib are approved for the second-line treatment of NSCLC.
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The discovery of targetable mutations, the increasing use of maintenance strategies, and the introduction of immunotherapies has made the choice of second-line agents much more complicated.
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Ramucirumab with docetaxel is the only combination regimen that has shown improved overall survival in the second-line setting.
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Erlotinib is the only agent approved in the third-line setting for EGFR wild-type patients.