Aaron M. Goodman, MD
In a study reported in JAMA Oncology, Aaron M. Goodman, MD, of the University of California, San Diego Moores Center for Personalized Cancer Therapy, and colleagues 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.
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 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 [tumor mutational burden].” ■