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).

Abstract

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 (%) = 30:64:6; prior radiation = 93%; prior chemotherapy = 46%; ex-smoker/current smoker = 86%. In 68 pts evaluable for toxicity, treatment-related adverse events (TRAEs) led to drug discontinuation in 7 (10%), dose reduction in 19 (28%) and interruption in 26 (38%). The most frequent grade 1 and 2 TRAEs were (% of pts): diarrhea (71%), dermatitis acneiform (63%), dry skin (44%), stomatitis (32%), fatigue (31%), pruritis (28%) and hand-foot reaction (26%). Gr 3 TRAEs > 3% included: diarrhea (13%), fatigue (9%), dermatitis acneiform (7%) and hand-foot reaction (4%). Among the first 56 evaluable pts, 6 pts (11%) achieved a partial response (median duration = 4.3 months); 35 pts (63%) had stable disease, of which 6 pts (11%) maintained disease stabilization ≥ 24 weeks. Data for all 69 pts at time of submission: median PFS = 2.8 months (95% C.I. 2.6-4.1 months), 6-month PFS =15% (95% C.I. 5-29%), and median survival = 7.6 months (95% C.I. 6.4-12 months). PK and biomarker analyses will be presented. Conclusions: Primary endpoint was met and toxicity profile was manageable. Antitumor activity of PF is consistent with EGFR TKIs, with ongoing molecular characterization of EGFRvIII mutations to evaluate potential as a biomarker of clinical activity.