Immune checkpoint-inhibitors and chemoradiation in stage III unresectable non-small cell lung cancer

Lung cancer resulted in an estimated 1.8 million deaths worldwide in 2018 and approximately 20% of patients with non-small cell lung cancer (NSCLC) are diagnosed with stage III unresectable disease. Phase III data from the PACIFIC trial show significantly improved progression-free survival for the checkpoint-inhibitor durvalumab given as consolidation following definitive chemoradiotherapy (cCRT). Overall survival results from this study have now been reported, along with outcomes from other phase II trials. A thorough review of the efficacy and safety of checkpoint-inhibitors used in conjunction with cCRT for stage III unresectable NSCLC is needed. Published and presented literature on phase II and III data was identified using the key search terms "non-small cell lung cancer" AND "checkpoint-inhibitors" (OR respective aliases). One randomized phase III clinical trial and three phase II trials reporting outcomes of checkpoint-inhibitors in conjunction with cCRT for stage III unresectable NSCLC were identified. PACIFIC reported significantly improved overall survival for consolidation durvalumab following cCRT compared with placebo. Although discontinuation due to adverse events (AEs) was higher with durvalumab, rates of grade 3/4 pneumonitis or radiation pneumonitis were low and comparable between arms. Results from phase II trials also show promising activity for other checkpoint-inhibitors and alternative sequencing strategies, although these need to be confirmed in a randomized context. Preliminary data suggest differences in the safety profiles between PD-1 and PD-L1 inhibitors. Currently, the role of PD-L1 expression levels for patient selection in this setting remains unclear, and durvalumab should be administered on an individual basis in patients with known driver mutations. Consolidation durvalumab following cCRT significantly improves overall survival with an acceptable safety profile in patients with stage III unresectable NSCLC, now representing a new standard of care.