Study suggests erlotinib’s potential in treating HNSCC

Past trials have shown there to be little benefit from epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors in unselected patients with head-and-neck squamous cell carcinoma (HNSCC). A recent study, however, reports on a patient with stage IV-A HNSCC who received 13 days of neo-adjuvant erlotinib and experienced a near-complete histologic response.

With the objective of determining a mechanism of exceptional response to erlotinib therapy in an HNSCC case, the research team isolated a single patient with locally advanced HNSCC who received erlotinib monotherapy in a window-of-opportunity clinical trial. Whole-exome sequencing of pretreatment tumor and germline patient samples was performed at an academic medical center, and a candidate somatic variant was experimentally investigated for mediating erlotinib response.

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The researchers observed no EGFR alterations in the pre-treatment tumor DNA. Paradoxically, they write, the tumor harbored an activating MAPK1 E322K mutation, which predicts ERK activation and erlotinib resistance in EGFR-mutant lung cancer. The HNSCC cells with MAPK1 E322K exhibited enhanced EGFR phosphorylation and erlotinib sensitivity compared with wild-type MAPK1 cells.

The researchers conclude that selective erlotinib use in HNSCC cases may be informed by precision oncology approaches.

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“The most significant finding is that genetic mutations that confer sensitivity to molecular targeting agents are unlikely to be restricted to specific tumors, implying that we need to broaden our understanding of how we treat all cancers,” study author Jennifer R. Grandis, M.D., of the University of Pittsburgh School of Medicine, tells Dermatology Times. “The mutation in this patient’s tumor is only present in 1 to 2% of head-and-neck cancers but in about 10% of cervical cancers, indicating that cancers in different sites may have more in common with each other than cancers that arise in the same site.”

The study was published online March 5 in JAMA Oncology. 

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