Virtual Library

Start Your Search

Angelica Rigutto

Author of

  • +

    P1.13 - Targeted Therapy (Not CME Accredited Session) (ID 945)

    • Event: WCLC 2018
    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/24/2018, 16:45 - 18:00, Exhibit Hall
    • +

      P1.13-20 - MET Protein Expression and Activation During Targeted Therapy in EGFR Mutated Lung Adenocarcinoma (ID 13478)

      16:45 - 18:00  |  Author(s): Angelica Rigutto

      • Abstract
      • Slides


      In EGFR mutated (EGFRm) lung adenocarcinoma (ADC) the tyrosine kinase (TK) receptor MET is involved in acquired resistance to anti-EGFR treatment. We analyzed MET protein expression and activation in EGFRm lung ADC treated with TK inhibitors (TKI).

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Patients with advanced EGFRm lung ADC, treated at the Oncology Department - San Luigi Hospital, who underwent tissue biopsy for diagnosis and tissue re-biopsy at disease progression for T790M test (after a negative liquid biopsy) were selected. c-MET (clone SP44) and phosphorylated (p-) MET (Tyr1234/1235, D26) expression was analyzed by immunohistochemistry and evaluated as H-Score (HS).

      4c3880bb027f159e801041b1021e88e8 Result

      Tumor tissues from 18 advanced EGFRm patients (12 female and 6 male; mean age 59 years) were available. On April 2018, 10 patients were alive and 8 were died. 11/18 (61%) cases harbored a T790M point mutation (T790M+) detected at tissue re-biopsy.

      At the baseline tumor tissue, lower c-MET expression levels were found in T790M+ (mean HS value= 135, range 40-250) compared to the T790M negative (T790M-) group (mean HS value= 226, range 100-300) (p=0.02). Furthermore, in T790M+ patients p-MET was expressed in 2/11 cases (18%, HS values=5 and 60) while in the T790M- group p-MET was expressed in 3/7 (43%, HS values=5, 240 and 240) cases (although with no significant p value).

      After first line TKI treatment, in the T790M+ group c-MET expression (mean HS value=140, range 5-300) was augmented in 7 and reduced in 4 cases, while p-MET was positive in 2/11 cases (HS values of 300 and 30). No significant differences in survival were found.

      In the T790M- group the c-MET mean HS value was 152 (range 30-300) and the 4/7 cases with higher c-MET expression levels (HS> 152) had a significant shorter PFS (p=0.02, HR=0.3, median survival: 7.5 vs 24 months). Furthermore, in this group p-MET positivity was maintained in the same 3 cases (with HS values= 240, 180, 10) and the two patients with higher MET activation had short PFS (9 and 6 months) at first line TKI treatment.

      8eea62084ca7e541d918e823422bd82e Conclusion

      Our preliminary analyses suggest that a strong expression of basal c-MET receptor in advanced EGFRm ADC may predict a T790M negative status at disease progression. Furthermore MET higher expression and activation may play a role in acquired resistance to TKI, although a limited number of cases have been analyzed. Thereby, we propose to monitor MET status along treatment and to reconsider MET-directed therapies for a well-selected subset of EGFRm lung ADC patients.


      Only Active Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login or select "Add to Cart" and proceed to checkout.