Profiles in courage.

Top Line: Genomic classifiers of radiation sensitivity (or the radiation sensitivity index, RSI) can be used to derive an optimal radiation dose for non-small cell lung cancer (NSCLC). What else can we optimize?

The Study: The RSI analyzes 10 index genes associated with NSCLC radiosensitivity. KEAP1 and NFE2L2 are also genes associated with radioresistance (although they aren’t in the RSI). This retrospective study of 120 patients treated with either chemoradiation (CRT) alone or CRT followed by durvalumab sought to determine if the addition of durvalumab improves locoregional failure (LRF) typically associated with KEAP1/NFE2L2 radioresistance mutations. Overall, CRT had twice the rate of LRF at 12 months compared to CRT with durvalumab (39% vs 18%). Tumor profiling revealed 37% of CRT patients and 27% of CRT with durvalumab patients had KEAP1/NFE2L2 mutations. Durvalumab appeared to counter the negative effect of KEAP1/NFE2L2 mutation. While LRF was significantly worse for patients with KEAP1/NFE2L2 mutation who received CRT alone, there was no difference in LRF among those who received durvalumab. Coupled with previous data, the question now becomes whether outcomes can be further improved by using genomic classifiers to personalize both maintenance immune checkpoint inhibition and radiation dose escalation in these patients.

TBL: Maintenance durvalumab appears to improve locoregional control in patients with radioresistant molecular phenotypes of NSCLC. | Shaverdian, J Thorac Oncol 2021