Genetic alterations associated with immunotherapy response in advanced NSCLC


MYSTIC trial is a randomized phase III trial that compares durvalumab monotherapy (D) or durvalumab plus tremelimumab combination therapy (D+T) with platinum-based chemotherapy (CT) in treatment naïve advanced non-small cell lung cancer (NSCLC). Although the overall survival didn’t reach statistical significance, the clinical benefits were shown in subgroup analysis. Among patients with blood tumor mutational burden ≥ 20 (bTMB≥ 20), the 1-year overall survival were 48.1%, 33.8% and 19.4% in D+T, D and CT group, respectively. bTMB≥ 20 was associated with improved median overall survival (D+T vs CT: HR=0.49 [95% CI 0.32, 0.74]; D vs CT: HR=0.72 [95% CI 0.50, 1.05]). Furthermore, the results of the specific genetic analysis were reported at the 2019 World Conference on Lung Cancer (WCLC). The mutation of STK11, KEAP1 and ARID1A were analyzed in this study. In patients with STK11 or KEAP1 mutation, the median overall survival was shorter than patients with wild type STK11 or KEAP1, irrespective of treatment received. In patients who received D+T treatment, the median overall survival was longer in ARID1A mutation group than ARID1A wild type (D, 8.6 vs 13.6 m; D+T, 23.2 vs 9.8 m; CT, 10.6 vs 12.4 m). These results revealed that genetic information is associated with immunotherapy response in advanced NSCLC.

Source : Rizvi N, et al. WCLC 2019