Laura Pike

Cediranib Plus FOLFOX/CAPOX Versus Placebo Plus FOLFOX/CAPOX in Patients With Previously Untreated Metastatic Colorectal Cancer: A Randomized, Double-Blind, Phase III Study (HORIZON II)

PURPOSE Cediranib is a highly potent inhibitor of vascular endothelial growth factor (VEGF) signaling with activity against all three VEGF receptors. HORIZON II [Cediranib (AZD2171, RECENTIN) in Addition to Chemotherapy Versus Placebo Plus Chemotherapy in Patients With Untreated Metastatic Colorectal Cancer] assessed infusional fluorouracil, leucovorin, and oxaliplatin/capecitabine and oxaliplatin (FOLFOX/CAPOX) with or without cediranib in patients with previously untreated metastatic colorectal cancer (mCRC). PATIENTS AND METHODS Eligible patients were initially randomly assigned 1:1:1 to receive cediranib (20 or 30 mg per day) or placebo plus FOLFOX/CAPOX. In an early analysis of this and two other cediranib studies (HORIZON I [Cediranib Plus FOLFOX6 Versus Bevacizumab Plus FOLFOX6 in Patients With Previously Treated Metastatic Colorectal Cancer] and HORIZON III [Cediranib Plus FOLFOX6 Versus Bevacizumab Plus FOLFOX6 in Patients With Untreated Metastatic Colorectal Cancer]), the 20-mg dose met the predefined criteria for continuation. Subsequent patients were randomly assigned 2:1 to the cediranib 20 mg or placebo arms. Progression-free survival (PFS) and overall survival (OS) were coprimary end points. RESULTS In all, 860 patients received cediranib 20 mg (n = 502) or placebo (n = 358). The addition of cediranib to FOLFOX/CAPOX resulted in PFS prolongation (hazard ratio [HR], 0.84; 95% CI, 0.73 to 0.98; P = .0121; median PFS, 8.6 months for cediranib v 8.3 months for placebo) but had no impact on OS (HR, 0.94; 95% CI, 0.79 to 1.12; P = .5707; median OS, 19.7 months for cediranib v 18.9 months for placebo). There were no significant differences in the secondary end points of objective response rate, duration of response, or liver resection rate. Median chemotherapy dose-intensity was decreased by approximately 10% in patients treated with cediranib. Adverse events (AEs) associated with cediranib were manageable. CONCLUSION Addition of cediranib 20 mg to FOLFOX/CAPOX resulted in a modest PFS prolongation, but no significant difference in OS. The cediranib AE profile was consistent with those from previous studies. Because of the lack of improvement in OS, cediranib plus an oxaliplatin-based regimen cannot be recommended as a treatment for patients with mCRC.

Cediranib monotherapy in patients with advanced renal cell carcinoma: Results of a randomised phase II study

BACKGROUND Cediranib is a highly potent vascular endothelial growth factor (VEGF) signalling inhibitor with activity against VEGF receptors 1, 2 and 3. This Phase II, randomised, double-blind, parallel-group study compared the efficacy of cediranib with placebo in patients with metastatic or recurrent clear cell renal cell carcinoma who had not previously received a VEGF signalling inhibitor. METHODS Patients were randomised (3:1) to cediranib 45 mg/day or placebo. The primary objective was comparison of change from baseline in tumour size after 12 weeks of therapy. Secondary objectives included response rate and duration, progression-free survival (PFS) and safety and tolerability. Patients in the placebo group could cross over to open-label cediranib at 12 weeks or earlier if their disease had progressed. This study has been completed and is registered with ClinicalTrials.gov, number NCT00423332. FINDINGS Patients (n=71) were randomised to receive cediranib (n=53) or placebo (n=18). The primary study outcome revealed that, after 12weeks of therapy, there was a significant difference in mean percentage change from baseline in tumour size between the cediranib (-20%) and placebo (+20%) arms (p<0.0001). Eighteen patients (34%) on cediranib achieved a partial response and 25 (47%) experienced stable disease. Cediranib treatment prolonged PFS significantly compared with placebo (hazard ratio (HR)=0.45, 90%confidence interval: 0.26-0.76, p=0.017; median PFS 12.1 versus 2.8 months). The most common adverse events in patients receiving cediranib were diarrhoea (74%), hypertension (64%), fatigue (58%) and dysphonia (58%). INTERPRETATION Cediranib monotherapy demonstrated significant evidence of antitumour activity in patients with advanced renal cell carcinoma. The adverse event profile was consistent with previous studies of cediranib 45 mg.

Stage I of a phase 2 study assessing the efficacy, safety, and tolerability of barasertib (AZD1152) versus low-dose cytosine arabinoside in elderly patients with acute myeloid leukemia

In this phase 2 study, the authors evaluated the efficacy, safety, and tolerability of the Aurora B kinase inhibitor barasertib compared with low‐dose cytosine arabinoside (LDAC) in patients aged ≥60 years with acute myeloid leukemia (AML).

Stage I of a phase 2 study assessing the efficacy, safety, and tolerability of barasertib (AZD1152) versus low-dose cytosine arabinoside in elderly patients with acute myeloid leukemia: Barasertib vs LDAC in AML

In this phase 2 study, the authors evaluated the efficacy, safety, and tolerability of the Aurora B kinase inhibitor barasertib compared with low‐dose cytosine arabinoside (LDAC) in patients aged ≥60 years with acute myeloid leukemia (AML).

Stage I of Phase II study assessing efficacy, safety and tolerability of barasertib (AZD1152) versus LDAC in elderly AML patients

In this phase 2 study, the authors evaluated the efficacy, safety, and tolerability of the Aurora B kinase inhibitor barasertib compared with low‐dose cytosine arabinoside (LDAC) in patients aged ≥60 years with acute myeloid leukemia (AML).