Author of

• 18739

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  P3.06 - Poster Session with Presenters Present (ID 492)

  • Event: WCLC 2016
  • Type: Poster Presenters Present
  • Track: Trial Design/Statistics
  • Presentations: 1
  • Moderators:
  • Coordinates: 12/07/2016, 14:30 - 15:45, Hall B (Poster Area)

  • 18846

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    P3.06-010 - Clinical Outcomes of Non-Small Cell Lung Cancer (NSCLC) Patients with ALK Co-Mutations (EGFR or KRAS) Receiving Tyrosine Kinase Inhibitors (TKI) (ID 4729)

    14:30 - 14:30  |  Author(s): S. Schmid
    • Abstract

    Background:
    Anaplastic lymphoma kinase (ALK) rearrangements with concurrent epidermal growth factor (EGFR) or Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations occur very rarely. Outcomes with TKI in these patients (pts) are poorly understood.
    
    Methods:
    Outcomes of pts with metastatic NSCLC and double mutations of ALK/EGFR or ALK/KRAS detected by FISH (ALK) and PCR or NGS (EGFR/KRAS) from six oncology centres in Switzerland were retrospectively analysed.
    
    Results:
    A total of 15 pts with adenocarcinoma were identified, 53% were females and tumor stages were IIIB (6%), IVA (27%) and IVB (67%). Six pts had a co-mutation of ALK/EGFR and nine ALK/KRAS. ALK/EGFR pts were younger (54 vs. 64 years) and less likely to be (ex-) smokers (34% vs. 77%). In total, 12 pts received an ALK-TKI (11x crizotinib, 1x alectinib, 2x ceritinib, 1x lorlatinib). EGFR-TKIs were given to five EGFR/ALK pts (4x afatinib, 2x osimertinib, 3x erlotinib). 33% received > 1 ALK-or EGFR-TKI. TKI were given as first-line (1L) in 40% (4x ALK/KRAS, 2x ALK/EGFR). Pts with ALK/KRAS co-mutation: Seven of eight pts (88%) were primary refractory to ALK-TKI treatment (all crizotinib). One patient has ongoing disease stabilization since 26 months. Three of six pts responded to 1L platinum-based chemotherapy with a median progression free survival (PFS) of 4.25 months (range: 1 month - NR). Pts with ALK/EGFR co-mutation: Two of four pts responded to ALK-TKI: one PR to crizotinib+erlotinib combination, one PR to alectinib and lorlatinib. Median PFS on first ALK-TKI was 3.75 months (range: 1-7months). Three of five pts (60%) achieved one or more responses to EGFR-TKI in different lines of therapy (4x PR: 3x afatinib, 1x osimertinib, CR: 1x osimertinib). Median PFS on first EGFR-TKI was 4.5 months (range: 3-7 months). Two of five pts responded to platinum-based chemotherapy (median PFS: 5.5 months (range: 0.25-10 months)).
    
    Conclusion:
    De novo concurrent ALK/KRAS alterations are associated with resistance to ALK-TKI treatment in seven out of eight pts, although one patient achieved ongoing disease stabilization for 26 months. Thus, platinum-based chemotherapy should be 1L treatment for these patients. In ALK/EGFR pts outcomes with ALK and EGFR-TKI seem inferior to what would be expected in pts with either alteration. EGFR-TKIs may potentially be more active compared to ALK-TKIs in ALK/EGFR pts. Worse outcomes to ALK-TKI may partly be related to false-positive ALK test results. Further studies are needed to clarify which patients may still benefit from the respective TKI.