Outcome of EGFR mutant patirnts included in a clinical trial after progression on EGFR TKI.

Abstract

e20555 Background: EGFR mutant(EGFRm) NSCLC patients develop adquired resistance after 12 months on EGFR TKI. Acquired T790mutation(T790M) is the most common mechanism of resistance in around 60% of patients, followed by MET amplification in 20% of cases. Inclusion in a clinical trials at progression may have an impact in patients’ outcome. Methods: We retrospectively assessed the overall survival in EGFRm patients according to post-progression treatment on 1st/2nd generation EGFR TKI: standard vs. experimental (clinical trial). Also, we assessed the survival in the cohort of acquired T790M NSCLC patients(p). X2 test and long rank test P values are described. OS was defined since progression 1st/2nd generation EGFR TKI to death or last follow up Results: 42p EGFRm were enrolled. According to EGFRm subtype (24 p EGFR del19, 14p EGFR L858R, 1p EGFR exon18, 1 EGFR exon20 ,2p unknown). Median age was 58 (33-83) and 27 (64%) females. First-line EGFR TKI was 30% gefitinib / 58 % erlotinib /10 % afatinib/2% dacotinib At PD, in 51 biopsies (b) were performed,11p were biopsy twice.Tumor tissue for molecular determinations was available in in 86% of cases. Druggable molecular alterations were detected in 57% of cases: 20 acquired T790M and 4 MET amplification. According to these results all 24 p were enrolled in a clinical trial (NCT02108964,NCT01802632,NCT02147990,NCT02335944, NCT02151981), and 18p were screening failure; 8p (45%) of them due to abscense of adquired resistance mechanisms. 10 received platinum-based chemotherapy and 6 only received best supportive care. OS metastatic disease was 51 months for patients included in a clinical trial vs 22 months for those on standard treatment (p < 0.001; 95%CI: 14.4-47). OS was: 34 months vs 10 months for those included in a clinical trial vs standard, respectively (p < 0.001; 95%CI: 8.88-25). For T790M tumours, OS post-progression was 25 months Conclusions: Enrolling patients in clinical trials may allow personalised treatment according to mechanisms of resistance improving survival after 1st/2nd generation EGFR TK progression disease.