Author of

• 31932

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  EP1.04 - Immuno-oncology (ID 194)

  • Event: WCLC 2019
  • Type: E-Poster Viewing in the Exhibit Hall
  • Track: Immuno-oncology
  • Presentations: 1
  • Now Available
  • Moderators:
  • Coordinates: 9/08/2019, 08:00 - 18:00, Exhibit Hall

  • 31945

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    EP1.04-11 - Frequency of Microsatellite Instability (MSI) in Brazilian TKI Non-Treatable Non-Small Cell Lung Cancer (NSCLC) Patients  (Now Available) (ID 2304)

    08:00 - 18:00  |  Author(s): Rodrigo de Oliveira Cavagna
    • Abstract
    • Slides

    Background
    

    Lung cancer is the most common cause of cancer deaths worldwide. Personalized medicine based on driver mutations has improved tailored treatment for patients with non-small cell lung cancer (NSCLC). However, only a subset of patients is benefited with tyrosine kinase inhibitors. Non-treatable advanced NSCLC patients may be eligible for treatment with immunotherapies. Recently, microsatellite instability (MSI) phenotype was reported as a predictive biomarker of response to immunotherapy, making it a crucial biomarker for clinical management for NSCLC patients. This study aimed to determine MSI frequencies in Brazilian NSCLC patients who are not eligible for TKi therapy.

    Method
    

    522 patients diagnosed with NSCLC patients at Barretos Cancer Hospital (Brazil) were evaluated. All samples were molecularly analyzed for EGFR (exons 18, 19, 20 and 21), KRAS (codons 12/13) and BRAF (exon 11 and 15) mutations by PCR followed by Sanger direct sequencing. The molecular MSI evaluation was performed using a hexa-plex marker panel by PCR followed by fragment analysis.

    Result
    

    The mean age of the patients was 61y (22-87) and 54% were male. EGFR, KRAS, and BRAF wild-type status were identified in 62.6% (327/522) of cases. In 297 EGFR/KRAS/BRAF wild-type cases, MSI analysis was performed and we observed the presence of MSI-H in only three (1%) cases. Overall, two out of these three patients were female and one was male, the age at the diagnosis ranged from 55 to 76 years old, they were current or former smokers and all three cases were diagnosed at stage IV. Of note, one of the patients with MSI-high status received treatment with immune checkpoint inhibitor, and he is the only one out of the three patients that remains alive with 51-months survival.

    Conclusion
    

    The frequency of MSI-high status is low in Brazilian NSCLC patients, in accordance with other population literature. Nevertheless, these MSI-positive patients are eligible for immunotherapy approaches.

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• 30780

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  P2.03 - Biology (ID 162)

  • Event: WCLC 2019
  • Type: Poster Viewing in the Exhibit Hall
  • Track: Biology
  • Presentations: 1
  • Moderators:
  • Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall

  • 30787

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    P2.03-07 - Frequency of Driver Genes (EGFR, KRAS, BRAF, ALK, RET and ROS1) Alterations in Brazilian Patients with Lung Adenocarcinoma (ID 1841)

    10:15 - 18:15  |  Author(s): Rodrigo de Oliveira Cavagna
    • Abstract

    Background
    

    Lung cancer is the deadliest cancer in the world. Several oncogenic drivers are observed in non-small cell lung cancer (NSCLC) and they have been used as therapeutic targets. The frequency of the major driver genes in lung adenocarcinoma varies based on ethnicity and the impact in the Brazilian admixture population has not been explored. Thus, we aimed to investigate the presence gene mutations of EGFR, KRAS, and BRAF, and ALK, RET and ROS1 rearrangements in Brazilian lung adenocarcinoma and to associate the presence of these alterations with clinicopathological characteristics and genetic ancestry.

    Method
    

    We evaluated 444 patients diagnosed with lung adenocarcinoma at Barretos Cancer Hospital. The presence of EGFR, KRAS and BRAF mutations in hotspot regions were evaluated by direct sequencing. For EGFR/KRAS/BRAF wild-type samples, we investigated the presence of ALK, RET and ROS1 rearrangements by the NanoString platform. Genetic ancestry was assessed by a multiplexed 46-ancestry informative markers panel. Stats: X² test and Cox regression model.

    Result
    

    Overall, 232 were male (52%) and 212 female (48%) and the average mean at diagnosis was 61 years. The majority of the patients were self-reported as white (77%), smokers (68%) and most patients were diagnosed at stage IV (74%). The median overall survival in patients at stage IV was 8.8 months. The frequency of EGFR mutations was 22.7% (n=101) and they were independently associated with never-smokers and Asian ancestry. KRAS mutations were found in 20.4% (n=91) of cases and were independently associated with smoking. The frequency BRAF mutations was of 1% (n=4), being all of them non-V600 BRAF. The frequency of ALK rearrangements was 2.25% (n=10) and was associated with younger age, the presence of metastases and advanced disease stage at diagnosis. RET and ROS1 rearrangements were only observed in 0.2% each (n=1/each) of cases. All the alterations identified in the oncogenic drivers were mutually exclusive.

    Conclusion
    

    The evaluation of the major driver genes for NSCLC, EGFR, KRAS, BRAF, ALK, RET and ROS1 can guide better clinical strategies for Brazilian lung adenocarcinoma, and the frequencies observed of these genes are in line with reported in other populations.