The following is a summary of “Clinicopathologic and Genomic Factors Impacting Efficacy of First-Line Chemoimmunotherapy in Advanced NSCLC,” published in the June 2023 issue of the Thoracic Oncology by Alessi et al.
Although programmed cell death protein 1 and programmed death-ligand 1 (PD-L1) blockade in combination with platinum-doublet chemotherapy has become the standard first-line treatment for advanced NSCLC, the factors associated with the efficacy of chemoimmunotherapy (CIT) are not well understood. This retrospective multicenter study collected clinicopathologic and genomic data from patients with advanced NSCLC (without sensitizing genomic alterations in EGFR and ALK). It correlated with clinical responses to first-line CIT.
A worsening performance status and an increasing derived neutrophil-to-lymphocyte ratio in the blood were associated with a substantially decreased objective response rate (ORR), median progression-free survival (mPFS), and median overall survival (mOS) among 1,285 patients treated with CIT. With increasing PD-L1 tumor proportion scores of less than 1%, 1% to 49%, 50% to 89%, and greater than or equal to 90%, there was a progressive improvement in ORR (32.7% versus 37.5% versus 51.6% versus 61.7%, P< 0.001), mPFS (5.0 versus 6.1 versus 6.8 versus 13.0 mo, P < 0.001), and generally mOS (12.9 versus 14.6 versus 34.7 versus 23.1 mo, P = 0.009), respectively. Among 789 NSCLCs with comprehensive genomic data, NSCLCs with a tumor mutational burden (TMB) greater than or equal to the 90th percentile had a better ORR (53.5% versus 36.4%, P = 0.004), mPFS (10.8 versus 5.5 mo, P< 0.001), and mOS (29.2 versus 13.1 mo, P<0.001).
The presence of an STK11, KEAP1, or SMARCA4 mutation was associated with significantly worse ORR, mPFS, and mOS to CIT (all P<0.05); this was also observed in the KRAS-mutant subgroup of NSCLCs with co-occurring STK11, KEAP1, or SMARCA4 mutations (all P < 0.05). In KRAS wild-type NSCLC, KEAP1 and SMARCA4 mutations were associated with a significantly shorter mPFS and mOS to CIT (all P < 0.05), but STK11 mutation status had no significant impact on mPFS (P = 0.16) or mOS (P = 0.38). In advanced NSCLC, a superior patient performance status, a low neutrophil-to-lymphocyte ratio, increasing PD-L1 expression, a very high TMB, and STK11/KEAP1/SMARCA4 wild-type status are associated with better clinical outcomes to first-line CIT.
Source: sciencedirect.com/science/article/abs/pii/S1556086423001211