Abstract 5900
Background
Although the dramatic activity of EGFR TKIs for EGFR-mutant ANSCLC, nearly 20% of pts do progress rapidly. Poor prognosis was demonstrated to be associated with TH, which may be mirrored by the co-existance of concomitant mutant drivers, such as PTEN. The aim of this analysis was to investigate the correlation between the loss of function of PTEN (as a mirror of TH), and the activity/efficacy of EGFR-TKIs for advanced EGFR mutant ANSCLC pts.
Methods
FFPE-tumor blocks of EGFR-mutant ANSCLC pts undergone upfront TKIs from 2015 to 2017 were retrospectively collected (follow-up >18 mo. was required for maturity). The status of 4 genes (PTEN, TP53, c-MET, IGFR) was evaluated by immunohistochemistry (IHC) and it was correlated with objective response rate (ORR), overall- and progression-free-survival (OS/PFS). Kaplan-Maier (KM) analysis was performed for independent factors at multivariate analysis.
Results
Forty-two EGFR-mutant ANSCLC pts were included [median age 65 yrs (42-86); M/F: 45/55%; current/former/never smoker: 13.5/35/51.5%; PS (ECOG) 0/1/2/3: 30/55/12.5/2.5%; GEF/AFA/ERL: 72.5/25/2.5%; del19/L858R/rare: 60/35/5%]. At multivariate analysis, PTEN loss (HR 6.02, 95% CI 2.48-14.5, p < 0.0001) and metastatic sites >2 (HR 2.38, 95% CI 1.01-5.62, p = 0.048) were significantly associated with shorter PFS. At KM analysis, pts with PTEN loss (13) had a median PFS of 2.0 mo. (95% CI 0-5.4) and a 1-year PFS of 7.7%, in comparison with pts without (27), median PFS 18.3 mo. (95% CI 16.5-20.1), 1-year PFS 69.6% (log-rank p < 0.0001). Coherently, at the multivariate analysis, PTEN loss (HR 5.11, 95% CI 2.06-12.6, p < 0.0001) and PS of 2-3 (HR 6.57, 95% CI 2.01-21.5, p < 0.002) were significantly associated with shorter OS. Pts with PTEN loss had a median OS of 4.5 mo. (95% CI 0.2-8.9) and a 1-year PFS of 15.4%, in comparison with pts without, median OS 26.9 mo. (95% CI 16.7-37.1), 1-year OS 81.5% (log-rank p < 0.0001).
Conclusions
A low-cost and reproducible IHC assay for PTEN-loss analysis represents a potential tool for identifying TH of EGFR-mutant ANSCLC pts. A powered clinical validation is currently ongoing.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Emilio Bria.
Funding
Comprehensive Cancer Center, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Università Cattolica del Sacro Cuore, Rome, Italy.
Disclosure
E. Bria: Advisory / Consultancy: Roche; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: MSD; Research grant / Funding (institution): AstraZeneca. All other authors have declared no conflicts of interest.
Resources from the same session
2935 - Correlation of progression free survival-2 and overall survival in solid tumors
Presenter: Paul Mainwaring
Session: Poster Display session 1
Resources:
Abstract
2273 - High performance of serial tumor biopsies in first in human (FIH) phase I trials.
Presenter: Jun Sato
Session: Poster Display session 1
Resources:
Abstract
5933 - Response rates and lesion-level progression patterns of solid tumor patients in an academic phase 1 program: implications for tumor heterogeneity
Presenter: Christopher Chen
Session: Poster Display session 1
Resources:
Abstract
3569 - Clinical Benefit and Response Rate in Early Phase Clinical Trials: First Report from a Single-Institution Study
Presenter: Antonio Marra
Session: Poster Display session 1
Resources:
Abstract
4139 - Patient (pt) selection for immunotherapeutic early-phase clinical trials (ieCTs): a single Phase I Unit experience
Presenter: Matteo Simonelli
Session: Poster Display session 1
Resources:
Abstract
4451 - Improving patient selection for immuno-oncology phase 1 trials: an external validation of five prognostic scores at Claudius Regaud Institute of Toulouse, Oncopôle (IUCT-O).
Presenter: Ghassan Al Darazi
Session: Poster Display session 1
Resources:
Abstract
1696 - Demonstrating the Changing Trends in Phase 1 Clinical Trials
Presenter: Christina Guo
Session: Poster Display session 1
Resources:
Abstract
3202 - Participation of Women in phase 1 oncology clinical trials
Presenter: Laura Vidal
Session: Poster Display session 1
Resources:
Abstract
4518 - Predictors for early trial discontinuation of patients with cancer participating in phase I clinical trials
Presenter: Joeri Douma
Session: Poster Display session 1
Resources:
Abstract
4368 - Safety of Tumor Treating Fields delivery to the torso: Meta analysis from TTFields clinical trials
Presenter: Federica Grosso
Session: Poster Display session 1
Resources:
Abstract