OS outcomes to anlotinib in patients (pts) with refractory NSCLC of both wild-type (WT) and mutant EGFR

Background: Anlotinib, a novel multi-targeted TKI targeting VEGFR, FGFR, PDGFR and c-Kit, significantly prolonged OS and PFS in ALTER0303 trial (NCT02388919) Here we report the efficacy of anlotinib on pts with different EGFR status. Methods: 437 pts progressed after at least 2 lines of prior therapies were randomized 2:1 to receive anlotinib or placebo till progression or intolerable toxicity. Pts harboring driven gene mutations must had received previous TKI therapies. EGFR status was determined as a pre-stratified factor. Results: Of 437 pts, 138 (31%) exhibited EGFR mutations and 299 (69%) presented WT. Anlotinib provided more benefit in OS on mutant EGFR pts than WT pts (table 1). Of 138 EGFR mutant pts, in anlotinib arm and placebo arm pre-treated by one EGFR-TKI were 91/93 (97.85%) and 42/45 (93.33%) (P= 0.33), respectively; pre-treated by two TKIs were 13 /93 (13.97%) and 8/45 (17.78%) (P= 0.86), respectively; pervious EGFR-TKI treatment in two arms was statistically equivalent. In 18 pts with T790 mutation, mPFS of 10 pts in anlotinib and 8 pts in placebo group were 3.27 vs. 0.83 month (P< 0.0001, HR = 0.044), and 1 pts received previous osimertinib (osim) therapy. For 3 -generation TKI, 7/93 in anlotinib arm and 3/45 in placebo arm underwent osim treatment revealed statistically equivalent at baseline (P= 0.40). The PFS of 7 pts in anlotinib and 3 pts in placebo arm with previous osim treatment were 4.00 vs. 0.40 month (P= 0.0076, HR = 0.108), and OS were 10.10 vs. 2.20 month (P= 0.03, HR = 0.071), respectively. In EGFR mutant pts, 21/93 (22.60%) in anlotinib arm and 12/45 (26.70%) in placebo arm received osim treatment after the end of ALTER 0303 trial and mean duration of treatment were 13.0 vs. 12.0 month, respectively (P= 0.7219). Conclusions: (1) Anlotinib presented significant improvement in OS on pts with refractory disease (resistant to 1 -generation TKI) of mutant EGFR comparing WT EGFR. (2) Anlotinib revealed an optimistical trend in PFS than placebo in pts with T790 mutation or resistance to osim. (Table Presented) .