Retinoblastoma mutation predicts poor outcomes in advanced non small cell lung cancer

The retinoblastoma gene ( RB 1 ) encodes the retinoblastoma ( RB ) pocket protein that plays an important role in cell cycle progression. Here we determine the frequency and prognostic significance of RB 1 mutation in non small cell lung cancer ( NSCLC ), restricting inclusion to Stage III and IV patients with linked genomic and clinical data. The primary outcome was median overall survival ( OS ). We identified RB 1 mutation in 8.2% of NSCLC patients. The median OS for wild‐type (wt) R B 1 was 28.3 months vs 8.3 months for mutant RB 1 (Hazard Ratio = 2.59, P  =   0.002). Of special interest, RB 1 mutation also correlated with lack of response to immunotherapy. Our study focused on RB 1 mutation in locally advanced and advanced non small cell lung cancer to better facilitate comparisons with small cell lung cancer ( SCLC ). In our SCLC cohort, RB 1 mutation was identified in 75% of patients and wt RB 1 was associated with significantly shorter OS ( P  =   0.002). The different outcomes of RB 1 mutation observed among lung cancer subtypes suggest a more complicated mechanism than simple regulation of cell cycle or response to chemotherapy.