High-dose icotinib in advanced lung adenocarcinoma(LUAD) patients harboring EGFR exon 21 L858R mutation: Real-world (RW) experience in a single center.

Abstract

e21036 Background: Non-small cell lung cancer(NSCLC) patients(pts) with epidermal growth factor receptor (EGFR) exon 19 deletion have more benefit from EGFR-tyrosine kinase inhibitors(EGFR-TKIs) compared to pts with EGFR exon 21 L858R mutation. Icotinib, which is a first-generation EGFR-TKI had been approved for use in EGFR-positive advanced NSCLC pts. A phase II trial(INCREASE trial) showed that high-dose icotinib 250mg tid(ico250) can effectively prolong the progression-free survival(PFS) of NSCLC pts with exon 21 L858R mutation without increased toxicity. However, the RW evidence is lacking. Methods: In this single-center, single-arm study, data were retrospectively collected from China-Japan Friendship Hospital. Pts with advanced LUAD, harboring EGFR exon 21 L858R mutation, and who received ico250 for more than 20 days without chemotherapy or immunotherapy were reviewed. Clinical data were analyzed for PFS, objective response rate(ORR), disease control rate(DCR), overall survival(OS), duration of treatment(DoT) and adverse events(AEs). Survival factors were evaluated by univariate and multivariate Cox regression analysis. Results: In total 40 pts(14M,26F; median age 67[46-86]; smoker:20.0%; ECOG performance status 0-1/2-3: 33/7) who received ico250 between 4/2019-11/2021 were analyzed. The median line of pre-ico therapies was 1(range 0-2). At the cut-off day, 29(72.5%) pts had discontinued ico250, and 7(17.5%) pts died. Overall, ORR was 30.0%, DCR was 80.0%, median DoT was 8.0mos (95%CI, 3.4-12.6), median PFS was 12.9mos (95%CI, 8.2-17.6) and median OS was not reached. The univariate and multivariate analysis showed that there was no significant and independent factor associated with PFS(all P> 0.05). 30(75.0%) pts experienced AEs, while the most common AEs were rash(24,60.0%), dry skin(9,22.5%), paronychia(8,20.0%) and diarrhea(6,15.0%). Grade 3/4 AEs in 6(15.0%) pts included AST/ALT elevation(3,7.5%), rash(2,5%), diarrhea(1,2.5%) and mucositis(1,2.5%)(1 suffered both rash and mucositis). 5(12.5%) pts discontinued high-dose icotinib due to AEs. Conclusions: These data add to the RW evidence that the efficacy and tolerability of ico250 in advanced LUAD pts harboring EGFR exon 21 L858R mutation. The efficacy results are consistent with the previous INCREASE trial. High-dose icotinib could be considered whatever the previous treatment and basic characteristics of LUAD pts with exon 21 L858R mutation. However, the higher incidence of grade3/4 AEs deserves special attention.