A Novel KIF5B-EGFR Fusion Variant in Non-Small-Cell Lung Cancer and Response to Afatinib: A Case Report

Abstract

Epidermal growth factor receptor (EGFR) fusions are rare genomic events in non-small-cell lung cancer (NSCLC). With advances in detection technology, some uncommon genomic mutation events, including EGFR fusions, have been detected. There are no standard treatment options for NSCLC patients harboring EGFR fusion. Herein, we report a case of KIF5B-EGFR fusion in NSCLC responding to tyrosine kinase inhibitors (TKIs). A 50-year-old male underwent left upper lobectomy followed by adjuvant chemotherapy for pathological stage IA3 lung adenocarcinoma. The tumor tissue was subjected to next-generation sequencing (NGS) and showed a KIF5B-EGFR fusion. When cancer recurrence occurred thirteen months later, the patient received afatinib (40 mg qd) as second-line treatment, and a partial response was observed, which resulted in an 11-month progression-free survival (PFS). This case provides valuable information on the response to afatinib in an NSCLC patient with a novel KIF5B-EGFR fusion. The NGS assay provides a powerful tool for identifying rare or atypical EGFR gene mutations in patients with NSCLC, which should be encouraged in clinical practice.

Fusion‐positive non‐small cell lung carcinoma: Biological principles, clinical practice, and diagnostic implications

“…Many other fusions can be exceptionally detected in other genes in NSCLC patients, such as BRAF, EGFR , and FGFR fusions 111–118 . Despite the very low frequency, it may be of strong interest to look for these gene rearrangements, since targeted therapy could be administered to these NSCLC patients.…”

“…With the rapid progress in improving NGS technology, EGFR fusions have been detected in a few subsets of NSCLC patients, representing between 0.05% and 0.15% of NSCLC 111,117,123,124 . Therefore, different EGFR fusions have been identified today in these patients including KIF5B::EGFR , RAD51::EGFR , TNS3::EGFR , SEPTIN14::EGFR , ZCCHC6::EGFR , SHC1::EGFR , and PURB::EGFR fusions 111,115,125 . Interestingly, some EGFR fusions showed sensitivity (partial response or disease stabilization) to different EGFR TKIs such as erlotinib, icotinib, or afatinib 115,124–129 …”

“…111,117,123,124 Therefore, different EGFR fusions have been identified today in these patients including KIF5B::EGFR, RAD51::EGFR, TNS3::EGFR, SEPTIN14::EGFR, ZCCHC6::EGFR, SHC1::EGFR, and PURB::EGFR fusions. 111,115,125 Interestingly, some EGFR fusions showed sensitivity (partial response or disease stabilization) to different EGFR TKIs such as erlotinib, icotinib, or afatinib. 115,[124][125][126][127][128][129] Alterations in FGFR have been reported in a multitude of solid malignancies, including breast, urothelial, melanoma, cholangiocarcinoma, prostate, and lung cancers.…”

“…110 Many other fusions can be exceptionally detected in other genes in NSCLC patients, such as BRAF, EGFR, and FGFR fusions. [111][112][113][114][115][116][117][118] Despite the very low frequency, it may be of strong interest to look for these gene rearrangements, since targeted therapy could be administered to these NSCLC patients. BRAF fusions, which represent a totally different mechanism compared to BRAF mutations, can be identified in different solid tumors such as melanoma, astrocytoma, thyroid cancer, colorectal and pancreatic carcinoma, and NS-NSCLC.…”

“…111,115,125 Interestingly, some EGFR fusions showed sensitivity (partial response or disease stabilization) to different EGFR TKIs such as erlotinib, icotinib, or afatinib. 115,[124][125][126][127][128][129] Alterations in FGFR have been reported in a multitude of solid malignancies, including breast, urothelial, melanoma, cholangiocarcinoma, prostate, and lung cancers. 130 FGFR fusions have been identified in around 0.2% of NSCLC with a higher frequency in squamous cell carcinoma (0.9%) than in adenocarcinoma (0.12%).…”