Horn L, et al. – Experts wanted to probe the continued use of afatinib with the addition of cetuximab after progression on afatinib in patients with epidermal growth factor receptor (EGFR) mutation–positive non–small–cell lung cancer (NSCLC) and acquired resistance to gefitinib or erlotinib. Findings outlined the predictable safety profile of sequential EGFR blockade with afatinib followed by afatinib plus cetuximab. Moreover, it exhibited modest activity in patients with EGFR mutation–positive NSCLC with resistance to erlotinib or gefitinib.

Methods

• Afatinib 40 mg daily until progression, followed by afatinib daily plus cetuximab 500 mg/m2 every 2 weeks until progression or intolerable adverse events (Aes) had been administered to patients with EGFR mutation-positive NSCLC who progressed on erlotinib or gefitinib.
• Safety, ORR, and PFS were the endpoints.

Results

• Afatinib monotherapy was given to thirty-seven patients.
• Response was noticed in two (5%) patients; median PFS was 2.7 months.
• It was noted that thirty-six patients transitioned to afatinib plus cetuximab.
• In addition, four (11%) patients responded; median PFS was 2.9 months.
• 4.9 versus 1.8 months (p=0.0354) was the median PFS with afatinib plus cetuximab for patients who received afatinib monotherapy for ≥12 versus <12 weeks, and for patients with T790M-positive versus T790M-negative tumors was 4.8 versus 1.8 months (p=0.1306).
• Drug-related grade 3/4 AEs were noticed in fifty percent of patients receiving afatinib plus cetuximab.
• Diarrhea (70%), rash (49%), and fatigue (35%) with afatinib monotherapy and rash (69%), paronychia (39%), and dry skin (36%) with afatinib plus cetuximab were the most frequent drug-related AEs (any grade).