A phase II study of multikinase inhibitor sorafenib in patients with relapsed non-small cell lung cancer (NSCLC)

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19084 Background: Sorafenib is a potent inhibitor of c-Raf, b-Raf VEGFR-1/2/3 and PDGFR-β. In NSCLC, proliferative signaling through the Ras/Raf/MEK/ERK pathway is often activated from K-ras mutations. We conducted a phase II study to determine the clinical and biological activity of Sorafenib in patients with relapsed NSCLC. Methods: Pts with recurrent NSCLC with measurable disease who have received no more than one prior chemotherapy regimen for metastatic disease, ECOG 0–2, and adequate organ function were eligible. Sorafenib was administered at a starting dose of 400 mg bid continuously on 28-day cycles. Dynamic contrast enhanced MRI (DCE- MRI) was performed before cycle 1 and at C1 day 15 to study early changes in tumor vascularity. Results: 15 pts enrolled, median age 64.5 yrs (range 35–84), 9 males, 6 females. Fourteen of 15 pts had only 1 prior platinum-doublet regimen; 1 pt had only prior erlotinib. No G4 toxicities have been observed. Hematological toxicity: G3 anemia (1 pt), G1–2 leukopenia (4 pts). G3 non-hematological adverse events: hyponatremia (3 pts), hypokalemia (1 pt), hypocalcemia (1 pt), hypophosphatemia (2 pt), nausea (1 pt), dyspnea/hypoxia (2 pt), syncope (1 pt), retinopathy (1 pt) and hypertension (1 pt). G1–2 non-hematological toxicities: hypertension, diarrhea, fatigue, elevated LFT’s, amylase and lipase. Skin toxicity has been seen in all pts and includes G1- 2: acne like drug-related rash (10 pts), hand-foot syndrome (7 pts), keratoacanthoma (1 pt) and vasculitis (1 pt); G3 hand-foot syndrome (2 pt). All toxicities have responded to temporary withdrawal of sorafenib and supportive care. 15 patients have completed at least 2 cycles of therapy and were evaluable for response (>8 weeks of treatment) and toxicity: 2 PR (13%) and 7 SD (46%), with a median time to progression of 5 months (range 1 -11+ months). DCE-MRI results: the DCE-MRI showed a reduction in the parameters of permeability, with decreased values in ktrans and kep, associated with reductions in the tumor size. Conclusions: Sorafenib monotherapy is well-tolerated with manageable toxicity and is active against relapsed NSCLC with only one prior line of systemic treatment. Accrual to this phase II trial continues in the second stage. No significant financial relationships to disclose.