First-line nivolumab (anti-PD-1) monotherapy in advanced NSCLC: the story of immune checkpoint inhibitors and “the sorcerers apprentice”

Non-small cell lung cancer (NSCLC) has usually been thought to be a non-immunogenic tumor, because early studies with Bacillus Calmette-Guerin, interleukin-2, or interferon have failed to demonstrate any benefit in NSCLC. Recently, some studies indicated that immune mechanisms play a vital role in the origin and development of lung cancer, and the abnormality of immune checkpoints would be the chief culprit. Immune checkpoint-inhibitors have shown promising activity in several solid tumors, including NSCLC. But interfering with the complex immune system in tumor immunosurveillance can trigger not only long lasting responses, but also severe and sometimes irreversible immunological side effects, as seen with the first approved cytotoxic T-lymphocyte antigen-4 (CTLA-4) inhibitor ipilimumab. This reminds one of a famous German poem written by Johann Wolfgang von Goethe in the year 1797, where an apprentice takes the opportunity to “play a little” with some magic when his master wizard had gone out of the house. But the apprentice summoned some powerful spirits he couldn’t actually control.