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With the evolving landscape of metastatic non-small cell lung cancer (NSCLC) treatment, standardized guidelines are invaluable in patient management. Current treatment strategies depend on the presence or absence of underlying oncogenic driver mutations. Patients with driver mutations are generally treated with first-line targeted therapies, with few exceptions. Those without driver mutations typically receive either combination chemo-immunotherapy or single-agent immunotherapy, depending on their PD-L1 status and overall health.

The review by Nikolaj Frost and Martin Reck in the delves into the treatment of non-oncogenic addicted metastatic NSCLC, supported by clinical trials. Despite ongoing development of targeted therapies, most metastatic NSCLC cases still lack targetable mutations, making chemo-immunotherapy the mainstay of treatment. Patients with high PD-L1 expression may be treated with immune checkpoint inhibitors (ICIs) alone, but most eventually develop resistance. Post-ICI resistance treatment is not well-established and is the topic of ongoing debate.

The paper addresses pertinent clinical questions: the optimal approach for PD-L1 high expressers, the significance of dual checkpoint blockade, and discontinuation strategies for long-term responders. It also explores second-line treatment after ICI failure and provides an overview of ongoing clinical trials that may reshape the first-line standard of care.

Arun Kumar, MD, is a hematology/oncology fellow PGY-6 at Medstar Georgetown University Hospital in Washington, D.C.; Raj Kanwal, MBBS, is an internal medicine residency applicant in the U.S.; and Zeeshan Solangi, MD, is a clinical instructor of medicine at Yale University Hospital in New Haven, Connecticut.

Read the review here and a Q&A related to it here.