Phase II trial of the irreversible oral pan-human EGF receptor (HER) inhibitor PF-00299804 (PF) as first-line treatment in recurrent and/or metastatic (RM) squamous cell carcinoma of the head and neck (SCCHN).

摘要: 5561 Background: PF is a potent, irreversible small molecule pan-HER tyrosine kinase inhibitor (TKI) with pre-clinical antitumor activity against EGFRvIII-mutated cell lines and xenograft models resistant to reversible EGFR TKIs. Methods: Eligible patients (pts) had untreated RM SCCHN with measurable disease and no prior anti-EGFR therapy. Paired biopsies as feasible were done for biomarkers; plasma was collected for PK. PF is administered at 45 mg p.o. every day in 21-day cycles. Primary endpoint is objective response rate (ORR), assessed every 6 weeks by RECIST 1.1. A Simon 2-stage trial design with H0: ORR ≤ 5% and Ha: ORR ≥ 15% stipulated that ≥ 2 responses must be observed in first 23 evaluable pts to proceed to stage II, ≥ 6 responses in first 56 evaluable pts to meet primary objective. Results: 69 pts are enrolled: median age 62 years (range: 40-82); M:F (%)= 88:12; ECOG 0:1:2 …