A randomized, open-label, phase II study of afatinib versus cetuximab in patients (pts) with recurrent or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC): Analysis of stage 2 (S2) following crossover.

Abstract

6001 Background: This open-label trial assessed the efficacy of the irreversible ErbB Family Blocker afatinib (A) vs cetuximab (C) in R/M HNSCC pts following failure of platinum-containing therapy. In Stage 1 (S1), A and C had confirmed objective response rates (RECIST 1.0) of 16.1% vs 6.5% by investigator review (8.1% vs 9.7% independent central review [ICR]; Seiwert TY, et al. MHNCS 2012. Abs 235). S2 data after crossover are presented. Methods: In S1, pts were randomized 1:1 to oral A 50 mg/day or IV C 250 mg/m 2 /wk (400 mg/m 2 IV loading dose) until progressive disease (PD) or intolerable drug-related adverse events (DRAEs). Pts could then crossover to the other treatment arm (S2), with treatment given until further PD or intolerable DRAEs. Tumor response in S2 (RECIST 1.0) was evaluated at 4 wks after crossover and every 8 wks thereafter. Results: 56% of pts crossed over into S2: 32 from A to C and 36 from C to A. Of these, 88% crossed over after PD and 12% after intolerable DRAEs. Baseline characteristics of S2 pts were similar in the A and C groups and treatment duration in S1 prior to crossover was comparable (A: 3.7 [0.2–15.7] months; C: 3.5 [0.0–12.5] months). Median treatment duration in S2 was 2.1 (0.0–7.6) months for A and 1.2 (0.0–9.9) months for C. Tumor size decreases of ≥30% were observed in 1 pt in each treatment group (ICR). The disease control rate (DCR) for A was 33% vs 19% for C and the median progression-free survival time was 9.3 wks for A and 5.7 wks for C (ICR). The most frequently reported DRAEs (≥20%) for A were rash/acne (56%), diarrhea (53%) and stomatitis (22%), and for C was rash/acne (44%). DRAEs of ≥Grade 3 were seen in 47% of pts treated with A and 16% of pts treated with C. 12 A-treated patients had dose reductions to 40 mg and 1 pt had a further dose reduction to 30 mg; no C-treated pts had dose reductions. Conclusions: R/M HNSCC pts seem to benefit from sequential therapy with A/C or C/A, especially when using A treatment after C failure. Cross resistance is not universally present and further investigation of sequential treatment is warranted. Clinical trial information: NCT00514943.