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P1.13 - Targeted Therapy (Not CME Accredited Session) (ID 945)
- Event: WCLC 2018
- Type: Poster Viewing in the Exhibit Hall
- Presentations: 1
- 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): Alessandro D'Aveni
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.6f8b794f3246b0c1e1780bb4d4d5dc53