Characteristics and outcomes of non-small cell lung cancer (NSCLC) patients (pts) carrying epidermal growth factor receptor (EGFR) mutations who progress after initial erlotinib (E) response

Abstract

Listen

Translate article

8064 Background: Most NSCLC pts with EGFR mutations respond to E; however, resistance to this tyrosine kinase inhibitor (TKI) can be acquired. The resistant T790M mutation has been identified in 50% of progressing pts. We assessed pt characteristics and outcome to additional treatment in 55 EGFR mutated pts after progression to E. Results: Pts mean age was 59±12.5 years; 65% females; 94% never-smokers; 54 adenocarcinoma. 35 pts (63%) were PS ≤2; main metastasis sites were lung (39/71%), bone (21/38%) and liver (10/18%). 22 and 25 pts received E as first- or second-line treatment, respectively. Mutations in tumor were: 65% DelE19 (Δ746–750), 35% L858R mutation; with 31% and 20% serum detection respectively. For the complete cohort, overall response rate (ORR) with E was 78% and time to progression (TTP) was 11.2 months (m) (range, 4–29 m). After progressing to E, 8 pts were re-biopsied, of whom 2 had the T790M mutation; 9 had the T790M mutation in serum (16%). 49% received platinum-based chemotherapy, 14.5% E plus another agent (bevacizumab, fulvestrant, vorinostat), 25.5% single-agent chemotherapy and 11% a non-reversible TKI (HKI-272). ORR for first-line post-E treatments was 33% (CR 1/PR 9) and median TTP was 8 m (range, 4.1–11.8 m). There were no differences in TTP according to gender (p = 0.10), type of mutation (p = 0.63) or severity of skin toxicity (p = 0.16). 11 pts received a second-line post-E treatment with E plus chemotherapy, achieving an ORR of 40%. Median survival was 27 m for all 55 pts (range, 22.9–31.1 m). Conclusions: Pts with EGFR mutations present a biologically different disease which continued to be sensitive to other treatments after progressing to E. No significant financial relationships to disclose.