In a study reported in JAMA Oncology, Goodman et al found amplification of PDL1 genes in 0.7% of solid tumors, including more than 100 tumor types. Response to checkpoint inhibition was high in a small group of patients with PDL1 amplification.
Prevalence of PDL1 Amplification
The study included next-generation sequencing analysis of 118,187 tumors from a deidentified database. Overall, PDL1 amplifications were found in 843 tumors (0.7%), including more than 100 types of solid tumors. Tumor types in which PDL1 amplification was more common included mixed hepatocellular cholangiocarcinoma (10.5%), breast carcinoma (1.9%), head and neck squamous cell carcinoma (3.1%), lung squamous cell carcinoma (1.7%), and undifferentiated soft-tissue sarcoma (3.9%). Cancers with lower frequencies of PDL1 copy number alterations included melanoma and colorectal, pancreatic, and prostate cancer. Most tumors with PDL1 amplification (84.8%) had a low to intermediate tumor mutational burden (TMB) and PDL1 amplification was not always correlated with high programmed cell death-ligand 1 (PD-L1) expression.
Response to Treatment
In a group of nine patients with PDL1-amplified solid tumors treated with a checkpoint inhibitor at one center, six (66.7%) had objective responses. Median progression-free survival was 15.2 months among all patients. Among responders, progression-free survival was ≥ 5.2 months in one patient with glioblastoma, ≥ 9 and 15.2 months in two with head and neck squamous cell cancer, 3 and ≥ 24.1 months in two with metastatic basal cell cancer, and ≥ 17.8 months in one with urothelial cancer.
The investigators concluded, “The results of this study suggest that PDL1 amplification occurs in a small subset of malignant tumors. Additional large-scale, prospective studies of PDL1-amplified cancers are warranted to confirm the responses to checkpoint blockade described herein, even in the absence of microsatellite instability, high PD-L1 expression, and a high TMB.”
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