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  P1.01 - Advanced NSCLC (Not CME Accredited Session) (ID 933)

  • Event: WCLC 2018
  • Type: Poster Viewing in the Exhibit Hall
  • Track:
  • Presentations: 1
  • Moderators:
  • Coordinates: 9/24/2018, 16:45 - 18:00, Exhibit Hall

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    P1.01-56 - Concurrent Mutations in Chinese Lung Cancer Patients Carrying HER2 Genomic Aberrations (ID 13756)

    16:45 - 18:00  |  Author(s): YUE Li
    • Abstract
    • Slides

    Background
    

    Although human epidermal growth factor receptor 2 (HER2, ERBB2) genomic aberration has been identified as therapeutic targets, clinical trials of HER2-directed therapies have disappointing results in lung cancer. We hypothesize that the concurrent alterations might be one of the reasons, thus the aim of this study was to describe frequent concurrent alterations in Chinese lung cancer patients harboring HER2 mutations.

    a9ded1e5ce5d75814730bb4caaf49419 Method
    

    A total of 147 cancer patients with HER2 mutations were enrolled in the study. Tumor biopsy, ctDNA and pleural effusion samples were collected for detection alterations using hybridization capture based next-generation sequencing (NGS), which enables the simultaneous detection of single-nucleotide variants, insertions/deletions, rearrangements, and copy-number alterations of at least 59 genes (59-1021).

    4c3880bb027f159e801041b1021e88e8 Result
    

    Sixty-two of 147 patients with HER2 genomic aberrations were diagnosed as lung cancer. The HER2 gene was amplified in 11 (18%) patients, whereas HER2 mutations were detected in 48 patients, co-occurrence of HER2 amplification and mutations were in 3 patients. Thirty of the 62 patients (48.39%) had concurrent actionable mutations across 18 genes, which involved in RTK-PIK3CA-mTOR signaling pathways, cell-cycle pathway, DNA repair pathway, RAS-RAF-MAPK pathway and some others (details in table). Moreover, 7 patients had more than 2 concurrent mutations besides HER2 mutation/amplification.

    Table 1. concurrent genetic alterations in HER2-altered lung cancer patients

    Signaling pathway	Concurrent actionable mutations	Number of patients
    RTK-PIK3CA-mTOR	EGFR	11
    	PIK3CA	4
    	STK11	2
    	FBXW7	1
    	TSC1	1
    	FLCN	1
    	C11orf30	1
    Cell-cycle	CDKN2A	5
    	CCND1	2
    	RB1	1
    DNA repair	BRCA2	1
    	ATM	1
    RAS-RAF-MAPK	BRAF	1
    	KRAS	1
    Others	MDM2	2
    	JAK2	2
    	SMARCA4	2
    	PTCH1	1

    8eea62084ca7e541d918e823422bd82e Conclusion
    

    Concurrent of actionable genetic alterations in HER2-altered Chinese lung cancer patients was common. The complex molecular profiles elucidate the importance of comprehensive analysis of genetic mutations when considering anti-HER2 targeted therapy.

    6f8b794f3246b0c1e1780bb4d4d5dc53

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