gms | German Medical Science

Introduction: Sorafenib is an oral multi-kinase inhibitor that targets the Raf/MEK/ERK pathway at the level of Raf kinase, and receptor tyrosine kinases VEGFR-2 and PDGFR-β to induce effects on the tumor and vasculature. Sorafenib has been shown to have antitumor activity in clinical studies in a variety of tumor types, including RCC, HCC, melanoma, and sarcoma. This study evaluated the anticancer effects and safety of sorafenib alone in patients with relapsed or refractory advanced NSCLC.

Methods: 54 patients aged ≥18 years with histologically or cytologically confirmed stage IV NSCLC, an ECOG PS of 0–2, and documented disease progression after prior treatment with 1–2 systemic anti-cancer therapies were enrolled in this multicenter Phase II study. Sorafenib 400 mg bid was administered to 52 patients in a continuous schedule until evidence of tumor progression or unacceptable drug-related toxicity. Primary endpoint was response rate according to RECIST. Tumor evaluations were performed at baseline and every 8 weeks.

Results: Patients were predominantly Caucasian (92%), 65% were male, and 94% had Stage IV NSCLC. Median age was 60.8 years and ECOG status was 0:1:2 in 10%:85%:6% of patients. The predominant histology was adenocarcinoma (54% of patients), followed by squamous cell carcinoma (31%). All patients had received prior systemic therapy (1:2:>2 therapies in 52%:44%:4% of patients). For efficacy analyses one patient was not eligible as a pancreatic cancer was detected post-screening.

4 partial responses were seen (response rate 8%) and tumor shrinkage below 30% in 11 patients (23%). The tumor stabilization rate (PR + NC) was 70.5%. Median progression-free survival (PFS) was 11.9 weeks and median time to progression was 14.9 weeks. Patients with SD had a median PFS of 24 weeks. All 52 patients were evaluable for safety. The most frequent drug-related adverse events were diarrhea (21 [40%] patients), hand–foot skin reaction (19 [37%]), fatigue (14 [27%]), and nausea (13 [25%]).Three patients discontinued due to adverse events (HFS, elevated lipase, and myocardial infarction, all possibly drug-related).

Conclusions: This Phase II study showed that treatment with sorafenib 400 mg bid was associated with a remarkable antitumor efficacy in pretreated patients with NSCLC and an acceptable safety and tolerability profile. Further investigation of sorafenib is warranted in controlled clinical trials.