Cancer of unknown primary with EGFR mutation successfully treated with targeted therapy directed by clinical next-generation sequencing: a case report

Abstract

Background Cancer of unknown primary (CUP) is usually treated with nonselective and empirical chemotherapy; however, its prognosis is generally poor, with a median survival of less than a year. Thus, clinicians eagerly await the development of more effective treatment strategies. In recent years, advances in next-generation sequencing (NGS) have made it possible to analyze comprehensively the genome of individual cancers. NGS has identified many genomic alterations, some of which are potential molecular targets of specific agents. We report a case of CUP that was successfully treated with targeted therapy directed by the genomic data obtained from an NGS-based multiplex assay. Case presentation A 52-year-old Asian woman with right hip joint pain underwent fluorodeoxyglucose-positron emission tomography/computed tomography, which showed multiple metastatic tumors in her right hip joint, thyroid gland, lung, and vertebrae. Brain magnetic resonance imaging showed multiple cerebral metastases. Additional tests, including pathology examination and conventional epidermal growth factor receptor (EGFR) gene mutation analysis (single-strand conformation polymorphism assay), could not identify the primary origin of the tumors, so the patient was diagnosed with CUP. After empirical chemotherapy for CUP, an NGS-based multiplex assay performed using a resected specimen of thyroid tumor detected the EGFR mutation c.2573 T > G p.Leu858Arg (L858R). Her treatment was changed to erlotinib, an EGFR tyrosine-kinase inhibiter, which dramatically shrank the tumors and decreased her serum carcinoembryonic antigen level. She achieved long-term disease control and survived for 2 years and 9 months from the first diagnosis. Conclusion This case might support the strategy that NGS-based multiplex assays could identify actionable molecular targets for individual patients with CUP.

Favorable Response to Olaparib in a Patient with Cancer of Unknown Primary Carrying a Germline BRCA1 R71K Mutation

“…19,20 Mitani et al reported successful treatment of a CUP patient with EGFR mutations under the guidance of NGS, achieving long-term disease control. 21 Here, we report a unique case of a CUP patient carrying a germline BRCA1 pathogenic mutation R71K, whereas the application of the PARP inhibitor olaparib has achieved good therapeutic effects. Although we performed extensive pathological examinations (eg, H&E stain and immunohistochemistry) and imaging technologies (eg, CT, MRI, and PET-CT scan), the primary site has not yet been identified, while additional workup such as direct internal organ visualization by an exploratory laparotomy may facilitate a definitive diagnosis.…”

Clinicopathological and Molecular Features of Secondary Cancer (Metastasis) to the Thyroid and Advances in Management

“…A total thyroidectomy was performed, and genetic profiling of the specimen revealed L858 and T790M EGFR mutations. Therapy was adjusted from erlotinib to osimertinib (another epidermal growth factor receptor tyrosine kinase for specific EGFR mutation) based on this, which resulted in clinical improvement [ 106 ]. In another case report, a patient with metastatic uveal melanoma to the thyroid was found to have BRAF mutation wild type [ 99 ].…”

Computational insights into the stereo-selectivity of catechins for the inhibition of the cancer therapeutic target EGFR kinase

“…The emergence of L858R as a potential biomarker holds promise for predicting the responsiveness of lung cancer models to anti-EGFR therapy ( Marrocco et al, 2023 ). Notably, the use of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) has demonstrated considerable efficacy in NSCLC patients harboring this mutation, offering a favorable side effect profile and contributing to an improved quality of life ( Mitani et al, 2020 ).…”