Prospective study of single nucleotide polymorfisms in PDCD1 impact on outcomes with pembrolizumab for metastatic lung adenocarcinoma

Pembrolizumab improves outcomes in metastatic lung adenocarcinom (MLA) expressing PD-L1. A multicenter prospective study in Italy evaluated the impact of certain single nucleotide polymorphisms (SNPs) in the PDCD1 gene (the programmed cell death 1 gene) on the efficacy of pembrolizumab. Among 141 patients, 71 with PD-L1 expression ≥ 50% received pembrolizumab monotherapy, whereas 70 with lower expression received pembrolizumab plus platinum-pemetrexed chemotherapy. Median progression-free survival (PFS) was 20 months (95% CI 13-27) overall, 25 months (16-34) with pembrolizumab, and 13 months (8-23) with combination therapy. The SNP rs7421861 was significantly associated with PFS: 23 months (95% CI 8-23) in A/A, 20 months (12-29) in A/G, and 6 months (3-11) in G/G patients. Moast G/G carriers (12/13) had stable or progressive disease, and OS was also inferior. The authors conclude that the rs7421861-G allele is associated with poorer outcomes in pembrolizumab-treated MLA patients.