Stage III Non-Small Cell Lung Cancer
The standard of care for stage III non-small cell lung cancer (NSCLC – locally advanced non-resectable) has been concurrent chemotherapy and radiotherapy. With this combined modality therapy, the five-year survival rate is between 15-30%.
It was noted that chemotherapy has several immunologic effects including induction of PD-L1 expression on tumor cells, while radiation enhances the activity of immunotherapy. Based on this observation the specific study was designed to add immunotherapy to chemoradiation. The stage III unresectable NSCLC patients that successfully completed the chemoradiation were started on durvalumab, an antiprogrammed cell death ligand-1 (PD-L1) antibody. The 12-month disease-free survival was 55% for the durvalumab arm compared with 35% for the placebo arm, and the 18-month disease free survival was 44% for the durvalumab arm compared with 27% for the placebo arm.
This treatment was beneficial regardless of the PD-L1 status. The time to distant metastasis or death also favored the durvalumab group with 23 months versus 14 months for the placebo arm.
Side effects from durvalumab are not common but can be severe and include pneumonitis, hepatitis, colitis, hormone gland problems, hepatitis, and rash. Based on this study durvalumab was FDA approved for stage III lung cancer post chemoradiation.
A smaller study LUN 14-179 tested standard chemotherapy options (cisplatin etoposide, carbo paclitaxel, cisplatin pemetrexed) with concurrent radiation followed by pembrolizumab up to one year.
The rate of severe pneumonitis was rare, but grade two toxicity was 10%. At 18 months there was improvement in both disease-free survival as well as overall survival in the pembrolizumab arm.
For stage III unresectable NSCLC concurrent chemoradiation followed by durvalumab has become the standard of care.