As is known, immune checkpoint inhibition plays only a limited role after failure of EGFR- or ALK-targeted treatment in patients with advanced NSCLC; this applies to both monotherapy and combinations with chemotherapy as demonstrated by the CheckMate 722 and KEYNOTE-789 trials.

In the setting of EGFR-mutated NSCLC, the third-generation EGFR TKI osimer­tinib is the current first-line standard of care, although eventual progression is virtually inevitable. Secondary EGFR and MET alterations have been found to account for 25 % to 50 % of cases of resistance.

The highly selective and potent RET kinase inhibitor selpercatinib has been implemented in the treatment of lung cancer harboring RET gene fusions. At the same time, the combination of platinum, pemetrexed and pembrolizumab is an established first-line standard of care for patients without EGFR or ALK alterations. The aim of the randomized, open-label, phase III LIBRETTO-431 study was to define the optimal first-line regimen for patients with RET-fusion–positive NSCLC.

Approximately 30 % to 40 % of patients with non–small-cell lung cancer (NSCLC) are diagnosed with resectable disease. Depending on the stage, the risk of disease recurrence remains high in spite of treatment, which calls for more effective strategies. For patients with resectable ALK-positive NSCLC, the guidelines recommend adjuvant platinum-based chemotherapy, while immunotherapy is not recommended.