IS8-3 - A Randomized, Open-Label, Phase II Study of Afatinib Versus Cetuximab in Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma (HNSCC)

Abstract

ABSTRACT Background In this study, afatinib (A) (BIBW 2992), an oral, irreversible ErbB Family Blocker was compared with cetuximab (C) in patients (patients) with recurrent/metastatic (R/M) HNSCC after platinum-based therapy failure. Methods Eligible patients were randomized to A 50 mg/day or C 400 mg/m2/week loading dose, then 250 mg/m2/week, until disease progression or treatment-related AEs (Stage 1 [S1]); patients could then crossover treatment arms (stage 2 [S2]). Primary end point was tumor shrinkage (maximal reduction in sum of longest diameters [SLD] of target lesions versus baseline), according to RECIST 1.0, at end of S1. Biomarkers (p16 and EGFRvIII) are also being evaluated in this study. Results One hundered twenty-four patients (median age 58.0 years, 87.1% male) were equally randomized. S1 mean tumor shrinkage (adjusted mean change [SE] versus baseline in SLD) by investigator review (IR): A, 3.86 [3.62] mm; C, 2.37 [3.47] mm (P = 0.761); and by independent central review (ICR): A, 9.88 [4.02] mm; C, 6.77 [4.14] mm (P = 0.574). IR objective response rates (ORRs) were ITT: 16.1% A versus 6.5% C (P = 0.09); evaluable patients: 19.2% A versus 7.3% C. ICR ORRs were ITT: 8.1% A versus 9.7% C (P = 0.78); evaluable patients: 9.6% versus 11.1%. Median PFS was 15.9 weeks for A versus 15.1 weeks for C (P = 0.93) by IR; 13.0 versus 15.0 weeks (P = 0.99) by ICR. At S2, 32 patients crossed from A; 36 from C. For S2, disease control rate (DCR): 38.9% (A as second treatment) versus 18.8% (C second) by IR; 33.3% versus 18.8% by ICR. The duration of DC: 20.2 versus 20.7 weeks by IR; 17.3 versus 16.6 weeks by ICR. All tumors were EGFRvIII (-) by qPCR (25 A, 28 C); p16 status: A 9 (+), 25 (-); C 8 (+), 23 (-). p16 (-) tumors showed higher RR for A versus C, by IR (20.0% versus 8.7%). One p16 (+) tumor responded to A. Most common treatment-related AEs in S1: diarrhea (A, n = 61: 78.7%; C, n = 60: 20.2%) and rash/acne (A: 78.7%; C: 76.6%). Patients with AEs leading to dose reduction: 25.5% A versus 3.3% C; patients with AEs leading to discontinuation: 37.7% A versus 16.7% C. Conclusions Afatinib is the first EGFR-TKI to show comparable antitumor activity to cetuximab in platinum-refractory R/M HNSCC. DC with afatinib after cetuximab failure is potentially clinically meaningful. Both afatinib and cetuximab showed characteristic safety profiles; more afatinib patients experienced diarrhea.