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A randomized , phase II study of afatinib versus cetuximab in metastatic or recurrent squamous cell carcinoma of the head and neck . BACKGROUND Afatinib is an oral , irreversible ErbB family blocker that has shown activity in epidermal growth factor receptor ( EGFR ) -mutated lung cancer . We hypothesized that the agent would have greater antitumor activity compared with cetuximab in recurrent or metastatic ( R/M ) head and neck squamous cell carcinoma ( HNSCC ) patients , whose disease has progressed after platinum-containing therapy . PATIENTS AND METHODS An open-label , randomized , phase II trial was conducted in 43 centers ; 124 patients were randomized ( 1 : 1 ) to either afatinib ( 50 mg/day ) or cetuximab ( 250 mg/m ( 2 ) /week ) until disease progression or intolerable adverse events ( AEs ) ( stage I ) , with optional crossover ( stage II ) . The primary end point was tumor shrinkage before crossover assessed by investigator ( IR ) and independent central review ( ICR ) . RESULTS A total of 121 patients were treated ( 61 afatinib , 60 cetuximab ) and 68 crossed over to stage II ( 32 and 36 respectively ) . In stage I , mean tumor shrinkage by IR/ICR was 10.4 % /16.6 % with afatinib and 5.4 % /10.1 % with cetuximab ( P = 0.46/0.30 ) . Objective response rate was 16.1 % /8.1 % with afatinib and 6.5 % /9.7 % with cetuximab ( IR/ICR ) . Comparable disease control rates were observed with afatinib ( 50 % ) and cetuximab ( 56.5 % ) by IR ; similar results were seen by ICR . Most common grade ≥3 drug-related AEs ( DRAEs ) were rash/acne ( 18 % versus 8.3 % ) , diarrhea ( 14.8 % versus 0 % ) , and stomatitis/mucositis ( 11.5 % versus 0 % ) with afatinib and cetuximab , respectively . Patients with DRAEs leading to treatment discontinuation were 23 % with afatinib and 5 % with cetuximab . In stage II , disease control rate ( IR/ICR ) was 38.9 % /33.3 % with afatinib and 18.8 % /18.8 % with cetuximab . CONCLUSION Afatinib showed antitumor activity comparable to cetuximab in R/M HNSCC in this exploratory phase II trial , although more patients on afatinib discontinued treatment due to AEs . Sequential EGFR/ErbB treatment with afatinib and cetuximab provided sustained clinical benefit in patients after crossover , suggesting a lack of cross-resistance .
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Intervention_Pharmacological
afatinib
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Intervention_Pharmacological
cetuximab
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Outcome_Physical
antitumor activity
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Outcome_Other
tumor shrinkage before crossover assessed by investigator
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Outcome_Other
independent central review ( ICR )
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Outcome_Physical
mean tumor shrinkage by IR/ICR
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Outcome_Other
Comparable disease control rates
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Participant_Condition
metastatic or recurrent squamous cell carcinoma of the head and neck
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Participant_Condition
recurrent or metastatic ( R/M ) head and neck squamous cell carcinoma ( HNSCC ) patients
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Participant_Condition
disease has progressed after platinum-containing therapy
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Participant_Sample-size
124 patients
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Participant_Sample-size
121 patients
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Participant_Sample-size
61 afatinib
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Participant_Sample-size
60 cetuximab
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Participant_Sample-size
68 crossed over to stage II
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Participant_Sample-size
32
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Participant_Sample-size
36