The progress that has been made in the last decades in the treatment of stage IV non-small cell lung cancer (NSCLC) has overall not been translated in the curative setting of stage I to III disease. In fact, the list of failed clinical trials aimed at improving the cure rates in this setting is long. The recent successes with immune checkpoint inhibition in stage IV NSCLC formed the basis to also study these agents in the curative setting. The first clinical trials to yield results in this setting evaluate immune checkpoint inhibition as consolidation treatment following chemoradiotherapy in locally advanced, unresectable NSCLC. The PACIFIC trial demonstrated that consolidation therapy with PD-L1 inhibitor durvalumab significantly prolongs both the progression-free (PFS) and overall survival (OS) compared to placebo in patients with disease control after chemoradiotherapy for stage III unresectable NSCLC. These findings have recently led to the EMA indication of durvalumab as a treatment of locally advanced, unresectable NSCLC patients whose tumors express PD-L1 on ≥1% of tumor cells and whose disease has not progressed following platinum-based chemoradiation therapy. In addition to this, recent phase II data show that consolidation pembrolizumab following concurrent chemoradiotherapy substantially prolongs the time to metastasis or death in patients with inoperable stage III NSCLC. Finally, the phase II ETOP NICOLAS trial demonstrated that the addition of nivolumab to concurrent chemoradiotherapy is safe and tolerable in stage III NSCLC with promising efficacy signals. Together all these data support the further exploration of immune checkpoint inhibition in the curative NSCLC setting. Several trials are currently ongoing, including studies on the potential of adjuvant immune checkpoint inhibition in stage II and IIIA disease and trials in the pre-operative setting.
