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D. Wu

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    Poster Session (ID 8)

    • Event: ACLC 2018
    • Type: Poster Session
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 11/07/2018, 00:00 - 00:00, Poster Hall
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      P011 - Concurrent ALK/EGFR Alterations in Chinese Lung Cancers: Frequency, Clinical Features, and Differential Response to Therapy (ID 152)

      00:00 - 00:00  |  Author(s): D. Wu

      • Abstract

      ALK rearrangement and EGFR alterations are oncogenic driver mutations in lung cancers. Generally considered mutually exclusive, some studies suggested that these two mutations might occur concomitantly. Limited studies have reported the underlying association of molecular features and drug response to EGFR-TKIs in lung cancers with such co-alterations. Here, we performed next-generation sequencing (NGS) analysis in Chinese lung cancer patients, and evaluated distinct features of EML4- vs. non-EML4-ALK fusions in EGFR-mutated cases.

      A retrospective review was performed on genomic profiling data from either tissue or plasma of 419 ALK-rearranged lung cancer patients, sequenced in a CLIA-certified laboratory from 2015 to 2017. Patient characteristics (n=21) and clinical outcomes of patients harboring concurrent EGFR and ALK alterations were collected.

      Among the 419 ALK-rearranged lung cancers, a total of 21 patients (5.01%) were detected harboring concurrent ALK and EGFR (exon 18-20) genomic alterations. The concomitant rate of EGFR in patients harboring EML4-ALK (3.06%, 11/359) was dramatically lower than in non-EML4-ALK patients (16.67%, 10/60, p<0.001). Four EML4-ALK and 1 non-EML4-ALK patients were found to have de novo ALK/EGFR co-mutations whereas 1 EML4-ALK and 3 non-EML4-ALK patients acquired their ALK alterations after EGFR TKI treatment. For dual-positive patients who received past EGFR-TKI with unknown ALK status before the treatment, EML4-ALK/EGFR patients (n=6) commonly had shorter PFS to EGFR-TKI as well as higher relative ALK/EGFR allele frequency compared to non-EML4-ALK/EGFR (n=6; mPFS, 5.45 vs 15 months, p=0.11; mRAF, 1.52 vs 0.41, p=0.01), suggesting that EML4-ALK was more likely to be de novo whereas non-EML4-ALK acquired after EGFR-TKI. In addition, we found that for 9 dual-positive patients who had prior first-generation EGFR-TKI treatment, the clinical efficacy of single TKI use varied greatly, and patients might benefit from combination therapy of ALK+EGFR TKIs.

      This study revealed that EML4-ALK/EGFR and non-EML4-ALK/EGFR co-alterations displayed distinct prevalence in Chinese lung cancer patients. Our analyses suggested that non-EML4-ALK might be an acquired gene alteration and function as a resistance mechanism to EGFR-TKI, which might explain the observed discrepancy in prevalence as our sequencing cohort consisted of both previously treated or untreated patients. In addition, we observed that patients with dual ALK/EGFR alterations may benefit from combinatorial TKIs therapy.