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Ref Type | Journal Article |
PMID | (30149884) |
Authors | Oh IJ, Hur JY, Park CK, Kim YC, Kim SJ, Lee MK, Kim HJ, Lee KY, Lee JC, Choi CM |
Title | Clinical Activity of Pan-HER Inhibitors Against HER2-Mutant Lung Adenocarcinoma. |
Journal | Clinical lung cancer |
Vol | 19 |
Issue | 5 |
Date | 2018 09 |
URL | |
Abstract Text | HER2 mutations are found in 2% to 4% of non-small-cell lung cancer cases and are usually mutually exclusive with other genetic alterations. We screened a large cohort of patients from multiple institutions in Korea, described the characteristics of HER2-mutant cases, and reported on several patients who were treated with pan-HER inhibitors.The study population consisted of 360 patients diagnosed with adenocarcinoma from 4 institutions in Korea from June 2015 to September 2016. Tissue specimens from all participants were screened by direct sequencing, and next-generation sequencing was conducted only on specimens that were positive in direct sequencing. HER2-targeted therapy, either poziotinib or afatinib, was orally administrated.Next-generation sequencing was conducted in 129 patients, and finally 29 (8.1%) patients with HER2 mutation were identified. Most patients were female (58.6%), had never smoked (70.0%), and had stage IV non-small-cell lung cancer (55.2%). For all patients, the histologic type was adenocarcinoma, with no coexisting EGFR or ALK alterations. The most common type of HER2 mutation (48.3%) was c.2326_2327insTGT in exon 20. A partial response was observed in 2 patients who received poziotinib and 1 patient who received afatinib. The main toxicities of the pan-HER inhibitors were nausea, diarrhea, and mucositis.HER2 mutation was estimated at a frequency of approximately 8.1% in Korean patients with adenocarcinoma in the absence of known driver mutations. Because some of the HER2-mutant cases responded to poziotinib or afatinib, further studies are warranted. |
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Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
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ERBB2 G776delinsVC | lung adenocarcinoma | predicted - sensitive | Poziotinib | Case Reports/Case Series | Actionable | In a Phase II trial, Poziotinib (HM781-36B) treatment resulted in a partial response in one patient and stable disease in another patient with lung adenocarcinoma harboring ERBB2 (HER2) G776delinsVC (PMID: 30149884; NCT02979821). | 30149884 |
ERBB2 N813D | lung adenocarcinoma | predicted - sensitive | Afatinib | Case Reports/Case Series | Actionable | In a Phase II trial, Gilotrif (afatinib) treatment resulted in partial response in a patient with lung adenocarcinoma harboring ERBB2 (HER2) N813D (PMID: 30149884; NCT02979821). | 30149884 |
ERBB2 Y772_A775dup | lung adenocarcinoma | predicted - sensitive | Poziotinib | Case Reports/Case Series | Actionable | In a Phase II trial, Poziotinib (HM781-36B) treatment resulted in one partial response, stable disease in one patient, and progressive disease in three patients with lung adenocarcinoma harboring ERBB2 (HER2) Y772_A775dup (reported as A775_G776insYVMA) (PMID: 30149884; NCT02979821). | 30149884 |
ERBB2 E812K | lung adenocarcinoma | predicted - sensitive | Poziotinib | Case Reports/Case Series | Actionable | In a Phase II trial, Poziotinib (HM781-36B) treatment resulted in stable disease in a patient with lung adenocarcinoma harboring ERBB2 (HER2) E812K (PMID: 30149884; NCT02979821). | 30149884 |