Efficacy and safety of PF299804 versus erlotinib (E): A global, randomized phase II trial in patients (pts) with advanced non-small cell lung cancer (NSCLC) after failure of chemotherapy (CT).
LBA7523 Background: PF299804, a potent, irreversible inhibitor of human epidermal growth factor receptor (HER)-1/EGFR, -2, and -4 tyrosine kinases (TK), is active in E-sensitive and -resistant preclinical models. PF299804 had clinical activity in phase I/II trials in EGFR TK inhibitor (TKI)-refractory NSCLC; a phase III trial is ongoing (BR26). The current trial compared efficacy and safety of PF299804 vs.E in pts with NSCLC after CT failure. Methods: Eligible pts (any histology, ECOG performance status [PS] 0–2, 1/2 CT regimen failures, no prior E, available tumor tissue) were randomized 1:1 to oral PF299804 45 mg or E 150 mg once daily and treated until progression/toxicity. Endpoints included progression-free survival (PFS; primary), overall survival (OS), objective response rate (ORR), safety, and KRAS/EGFR mutation (mu) status. Results: 188 pts (median age 60 years, 87% PS 0/1, 41% female, 65% adenocarcinoma (adeno), 25% East Asian, 21% non-smoker, 16% EGFR mu, 16% KRAS mu) were randomized. Baseline characteristics were balanced between arms except for PS 2 ( PF299804 , 20; E, 3 pts). Mu status determination rates were high (KRAS, 81%; EGFR, 77%). Median follow-up was 12 weeks. PF299804 showed significantly longer PFS vs. E in the overall population (p=0.017), with benefit consistent across several subgroups (SG) including EGFR wild type (wt). ORR favored PF299804 (17% vs. 4%; p=0.008). Frequent treatment-related adverse events (TRAEs) for PF299804 vs. E (grade, any/3 or 4): diarrhea (71%/11% v 48%/3%), acne (53%/7% vs. 34%/5%), and rash (26%/4% vs. 37%/2%). Eight pts discontinued due to TRAEs: PF299804 , 6; E, 2 pts. Conclusions: PF299804 showed significant improvement in PFS (primary endpoint) vs. E in all enrolled pts with NSCLC. Common EGFR TKI AEs were more frequent with PF299804. [Table: see text] [Table: see text]