Author of

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  P2.13 - Targeted Therapy (Not CME Accredited Session) (ID 962)

  • Event: WCLC 2018
  • Type: Poster Viewing in the Exhibit Hall
  • Track:
  • Presentations: 1
  • Moderators:
  • Coordinates: 9/25/2018, 16:45 - 18:00, Exhibit Hall

  • 27178

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    P2.13-06 - TP53 Status in Relation to Response to Anti-ALK Agents in Patients with EML4-ALK-Translocated NSCLC (ID 12580)

    16:45 - 18:00  |  Author(s): Maurizio Puccetti
    • Abstract
    • Slides

    Background
    

    Patients with non-small-cell lung cancer (NSCLC) carrying the EML4-ALK translocation are responsive to anti-ALK agents, such as crizotinib. However, about 30%-40% of patients show primary resistance to treatment. We previously demonstrated that TP53 mutations are associated with poorer prognosis in EGFR-mutated patients treated with tyrosine-kinase inhibitors. In the present study we analyzed the impact of TP53 mutations on response to anti-ALK treatment in EML4-ALK-translocated NSCLC

    a9ded1e5ce5d75814730bb4caaf49419 Method
    

    Eighty-three patients with EML4-ALK-translocated NSCLC identified in the Wide Catchment Area of Romagna between 2012 and 2016 were considered. TP53 status was evaluated in 61 patients on the basis of DNA availability. Of these, 28 patients received an anti-ALK agent as second-or-more-line treatment and follow-up data were available. TP53 status was analyzed in relation to disease control rate (DCR): complete response (CR), partial response (PR) or stable disease (SD).

    4c3880bb027f159e801041b1021e88e8 Result
    

    Overall, TP53 mutations were observed in 14 (23%) patients, 6 (43%) showing a mutation in exon 5, 1 (7%) in exon 6, 3 (21%) in exon 7 and 4 (28%) in exon 8. We found one insertion (7%), one deletion (7%) and 12 point mutations (86%). Of the 28 patients treated with an anti-ALK agent, 5 (20%) showed TP53 mutations, 2 (40%) in exon 5, 1 (20%) in exon 5 and 2 (40%) in exon 8. Clinical response was not evaluable in 3 patients due to rapid disease progression (2 had a stop mutation in exon 5 of TP53). DCR for the remaining 25 patients was 60% in those with TP53-mutated tumors and 92% in those with TP53 wild-type disease.

    8eea62084ca7e541d918e823422bd82e Conclusion
    

    TP53 mutations were associated with a poorer DCR in EML4-ALK-translocated NSCLC patients treated with an anti-ALK agent. These results highlight the potential role of TP53 in determining primary resistance to anti-ALK agents, and should be confirmed in a wider case series.

    6f8b794f3246b0c1e1780bb4d4d5dc53

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