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MANUEL Alva Bianchi



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    P2.14 - Targeted Therapy (ID 183)

    • Event: WCLC 2019
    • Type: Poster Viewing in the Exhibit Hall
    • Track: Targeted Therapy
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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      P2.14-29 - Clinical Impact of Next-Generation Sequencing (NGS) in Blood Liquid Biopsies for Treatment Decisions in Advanced NSCLC (ID 2803)

      10:15 - 18:15  |  Author(s): MANUEL Alva Bianchi

      • Abstract

      Background

      Blood-based NGS is emerging as either complementary or alternative to standard tissue genotyping in metastatic non-small-cell lung cancer (NSCLC). In cases where tissue is not enough to complete standard EGFR, ALK, and ROS1 testing, or when patients are tested as triple-negative for these genetic alterations, additional tumor genotyping can lead to the detection of further actionable mutations. Moreover, NGS provides valuable genomic information that could be used to select for immunotherapy in metastatic NSCLC.

      We aimed to describe the molecular findings obtained by liquid biopsy of a cohort of advanced NSCLC patients with unknown/negative EGFR, ALK and ROS1 and how the results modified treatment decisions.

      Method

      We performed a retrospective study of advanced NSCLC patients that were analyzed with NGS as part of a molecular pre-screening for clinicals trials in our institution in Madrid (Spain) between October 2016 and March 2019. Patients >18 years-old, PS ECOG 0-2, stage IIIC-IV NSCLC were routinely tested for EGFR, ALK, and ROS1, in addition to PD-L1 (22C3). Those wild-type for EGFR, ALK, or ROS1, or without enough tissue to perform the triple testing were considered for blood-based NGS. The different diagnostic assays for ctDNA NGS used depended on clinical trial molecular pre-screening protocol: Foundation One® Liquid or Guardant360®.

      We analyzed the frequency of oncogenic drivers, the proportion of patients treated with genotype-directed therapy, and survival.

      Result

      We analyzed 95 NSCLC pts with valid NGS results from ctDNA (blood sample).

      We detected 14 oncogenic driver mutations (15%): 5 EGFR (5.2%), 1 ALK fusion (1%), 1 BRAF V600E (1%), 2 METex14 (2.1%), 2 RET fusion (2.1%) and 3 HER2 mutations (3.2%). We also found 16 KRAS mutations (16.8%), and genetic alterations in tumor suppressor genes: 39 TP53 (41%), and 6 NF1 mutations (6.3%).

      So far 8/14 patients were treated with genotype-directed therapy (8.4%), 2 of them under clinical trial: 5 pts were treated with an anti-EGFR treatment, 2 pts received alectinib (1 pt for ALK rearrangement, 1 pt for RET rearrangement) and 1 pt with tepotinib (MET splice mutation)

      Of the 6 patients with NF1 mutations, 4 pts were women (66%), 5 pts were current smokers (83%), median age at diagnosis was 69 years (66-80), and 5 pts had non-squamous histology (83%). PDL1 tumor expression was determined in 4 patients: 2 pts >50%, 1 pt 10%, and 1 pt 0%. NF1 was co-mutated in 4 pts with RAS (66%), 1 with both RAS and TP53, and 1 HER2 A775:G776insYVMA.

      3/6 NF1 mutant patients were treated with single agent ICI: 2 pts with first-line pembrolizumab, and 1 pt second-line pembrolizumab. In addition, one patient with germline NF1 mutation was treated with 2nd line atezolizumab. All 3 pts obtained responded to ICI (1 pt with atypical response). We will present updated data on PFS and OS.

      Conclusion

      Blood-based NGS can guide treatment decisions in metastatic NSCLC, with special interest in those patients without enough tumor tissue, or wild-type to standard-tissue diagnostic tests. NF1 mutations in NSCLC could predict responses to immune-checkpoint inhibitors, and warrants further evaluation.