Current Standards and Clinical Trials in Systemic Therapy for Stage III Lung Cancer: What Is New?

Patients with stage III non-small cell lung cancer (NSCLC) comprise a heterogeneous group, some of whom have curable disease. Although surgery plays a role for some patients, the majority of fit patients will be treated with chemotherapy and radiation alone. The optimal therapy for all patients remains undefined, but certain principles of care are widely accepted. Specifically, concurrent chemoradiation is the standard of care for patients who are able to tolerate such therapy, namely those with a good performance status, minimal or no weight loss, and adequate end-organ function, including pulmonary reserve. The most commonly used chemotherapy regimens given in combination with radiation therapy are cisplatin/etoposide or carboplatin/paclitaxel. Studies incorporating newer agents have not improved outcomes when compared to these older regimens. The merits of chemotherapy administered beyond the conclusion of radiation therapy continue to be debated, but thus far randomized phase III trials have not provided supporting evidence for this strategy. Incorporating antiangiogenics with chemoradiation has proven to be ineffective in some cases and unsafe in others. Studies with targeted agents in unselected patient populations with stage III disease have also been disappointing. Despite these recent setbacks, however, there remains a sound rationale for incorporating molecularly targeted agents into chemoradiation regimens in select patient groups or consolidating chemoradiation with immunotherapy. Studies that incorporate drugs targeting EGFR, ALK, RAS, programmed cell death 1 (PD-1), and programmed death ligand 1 (PD-L1) into the management of patients with stage III NSCLC will be reviewed.