A multicenter phase II study of sorafenib in combination with erlotinib in patients with advanced non-small cell lung cancer (KCSG-0806)

• Targeting angiogenesis and EGFR pathway are important in non-small-cell lung cancer.
• We examine the efficacy and safety of sorafenib and erlotinib.
• Sorafenib combined with erlotinib is well-tolerated with manageable toxicity.
• Benefit in EGFR wild type patients warrant further investigation.

ObjectivesSorafenib and erlotinib are potent, orally administered receptor tyrosine kinase inhibitors with antiproliferative and antiangiogenic activities. Given their synergistic activity in combination, we conducted a phase II study to determine the clinical activity of sorafenib in combination with erlotinib in patients with advanced non-small cell lung cancer (NSCLC).Materials and methodsPatients with advanced NSCLC who have received one or two prior chemotherapy regimens for metastatic disease, ECOG 0–2, and adequate organ function were eligible. Patients received 400 mg twice daily sorafenib and 150 mg daily erlotinib in 28-day cycles. Epidermal growth factor receptor mutation and its downstream pathways were analyzed from available tumor samples. Changes in plasma cytokine and angiogenic factors were correlated with clinical outcomes.ResultsA total of 46 patients were enrolled. Twenty patients (43%) were never smokers and 35 patients (75%) had adenocarcinoma histology. The overall response rate was 30.4%. Response to sorafenib/erlotinib was observed more commonly in patients with EGFR mutation than in those with EGFR wild type (WT) or EGFR unknown tumors (62.5% vs. 6.7% vs. 34.8%; P = 0.013). Likewise, DCR was higher among patients with EGFR mutation than in those with EGFR WT or EGFR unknown tumors (87.5% vs. 46.7% vs. 60.9%; P = 0.161). The most frequent adverse events (AEs) of all grades were hand-foot skin reaction (67.4%) followed by acneiform rash (58.7%).ConclusionSorafenib combined with erlotinib is well-tolerated with manageable toxicity and appears to be effective against advanced NSCLC with one or two prior line of systemic treatment (NCT00801385).