R Burgess

BACKGROUND: Sunitinib malate (SUTENT) has promising single-agent activity given on Schedule 4/2 (4 weeks on treatment followed by 2 weeks off treatment) in advanced non-small cell lung cancer (NSCLC). METHODS: We examined the activity of sunitinib on a continuous daily dosing (CDD) schedule in an open-label, multicentre phase II study in patients with previously treated, advanced NSCLC. Patients > or =18 years with stage IIIB/IV NSCLC after failure with platinum-based chemotherapy, received sunitinib 37.5 mg per day. The primary end point was objective response rate (ORR). Secondary end points included progression-free survival (PFS), overall survival (OS), 1-year survival rate, and safety. RESULTS: Of 47 patients receiving sunitinib, one patient achieved a confirmed partial response (ORR 2.1% (95% confidence interval (CI) 0.1, 11.3)) and 11 (23.4%) had stable disease (SD) > or =8 weeks. Five patients had SD>6 months. Median PFS was 11.9 weeks (95% CI 8.6, 14.1) and median OS was 37.1 weeks (95% CI 31.1, 69.7). The 1-year survival probability was 38.4% (95% CI 24.2, 52.5). Treatment was generally well tolerated. CONCLUSIONS: The safety profile and time-to-event analyses, albeit relatively low response rate of 2%, suggest single-agent sunitinib on a CDD schedule may be a potential therapeutic agent for patients with advanced, refractory NSCLC.

4112 Background: Axitinib is an oral, potent and selective inhibitor of VEGF receptors 1, 2, and 3 that is being assessed in a broad range of tumors. This phase I portion of the study evaluated the safety and pharmacokinetics (PK) of axitinib in combination with BV and FOLFOX (oxaliplatin/5-fluorouracil [5-FU]/leucovorin) in pts with previously treated gastrointestinal and solid tumors. Methods: Pts in cohort 1 received BV 1 mg/kg, oxaliplatin 85 mg/m2, leucovorin 400 mg/m2, 5-FU 400 mg/m2 bolus then 2,400 mg/m2 by 46–48 h infusion, and axitinib at a starting dose of 5 mg PO BID. BV and FOLFOX were administered once every 2 weeks. Following demonstration of tolerability to BV 1 mg/kg in cohort 1, BV was escalated to doses of 2 mg/kg and 5 mg/kg in cohorts 2 and 3 respectively. Patients were evaluated for potential PK interactions between BV, FOLFOX, and axitinib. Safety and tumor response were also assessed. Results: Among pts enrolled in cohorts 1, 2, and 3 (n=15), 2 patients (13%) showed a partial response and 9 patients (60%) exhibited stable disease. The most frequently reported, treatment-emergent grade 3–5 adverse events were neutropenia (n=3), hypertension (n=3), and dyspnea (n=2). PK parameters and plasma profiles of BV, oxaliplatin, and 5-FU were similar in the presence or absence of axitinib, with mean (%CV) AUCinf for platinum clearance from ultrafiltrate of 7,155 ng.h/mL (74%) and 7,702 ng.h/mL (72%), respectively (n=14). Axitinib PK profiles were similar in the presence or absence of BV/FOLFOX. Conclusions: PK data indicate no evidence of an interaction between axitinib and BV/FOLFOX. Axitinib 5 mg BID in combination with BV 1 mg/kg or 2 mg/kg and FOLFOX was well tolerated. Tolerability data for combination treatment with the 5 mg BV dose await completion of patient enrollment into cohort 3. A 3-arm, randomized phase II study of axitinib/FOLFOX vs BV/FOLFOX vs axitinib/BV/FOLFOX in pts with metastatic colorectal cancer has been initiated. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Pfizer Pfizer

The outcome of patients with aggressive refractory diffuse large B-cell lymphoma (DLCL) is generally poor. A 43-year-old female with DLCL, who relapsed after first line chemotherapy (CHOP--cyclophosphamide, doxorubicin, vincristine, and prednisone) and progressed despite salvage chemotherapy (EPOCH-etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin), was treated effectively with 8 cycles of Rituximab. She is without evidence of disease with a follow-up of 32 months. We report this case to bring to attention the possibility of sustained durable remission with single agent Rituximab in refractory DLCL.

Reply: Ongoing under-reporting of clinically relevant safety data in phase II studies of tyrosine kinase inhibitors