FROM THE LITERATURE

Monoclonal Antibody Plus Interferon for Metastatic RCC

Bevacizumab(Avastin^®) plus interferon alfa (IFN) produces superior PFS and ORR in previously untreated patients with metastatic clear cell renal cell carcinoma (RCC) compared with IFN monotherapy according to results of a phase III trial of 732 patients. The prespecified stopping rule for OS, the primary endpoint, has not yet been reached. The median PFS was 8.5 months in patients treated with the combination vs. 5.2 months in those receiving IFN monotherapy (p<0.0001; HR=0.71). Bevacizumab plus IFN had a higher ORR of 25.5% compared to 13.1% with IFN monotherapy (p<0.0001). Overall toxicity was greater for the combination vs. IFN monotherapy, including significantly more grade 3 hypertension (9% vs. 0%), anorexia (17% vs. 8%), fatigue (35% vs. 28%), and proteinuria (13% vs. 0%). This trial validates antibody-mediated inhibition of the VEGF ligand as a clinically relevant strategy in RCC. The mechanism of these two agents may not be entirely independent, as IFN has demonstrated antiangiogenic effects.

JCO Early Release, published online ahead of print Oct. 20, 2008

Cardiac Toxicity of Second Generation TKIs in Patients
with Metastatic RCC

Sunitinib(Sutent^®) and sorafenib have considerable efficacy in metastatic RCC but TKI-associated cardiotoxicity has been reported in about 10% of the patients. Detailed cardiovascular monitoring during TKI treatment may reveal early signs of myocardial damage. Oncology health care providers need to recognize the signs and symptoms of cardiac damage in patients receiving these drugs. An observational study in Vienna, Austria analyzed all patients intended for TKI treatment for coronary artery disease (CAD) risk factors, history or evidence of CAD, hypertension, rhythm disturbances, and CHF. Monitoring included assessment of symptoms, ECGs, and biochemical markers (cardiac enzymes, troponin T). Echocardiograms were done at baseline and at time of a cardiac event (increased enzymes, symptomatic arrhythmia, new left ventricular dysfunction, or acute coronary syndrome). 86 patients received either sunitinib or sorafenib and among 74 eligible patients, 33.8% had a cardiac event, 40.5% had ECG changes, and 18% were symptomatic. Seven patients (9.4%) were seriously compromised and required intermediate care and/or ICU admission. All patients recovered after cardiovascular management and were considered eligible for TKI continuation. There was no significant survival difference between patients who experienced a cardiac event and those who did not have a cardiac event. The authors conclude that their observations indicate that cardiac damage from TKI treatment is a largely underestimated phenomenon, but is manageable if patients have careful cardiovascular monitoring and cardiac treatment at the first signs of myocardial damage.

JCO, Published Ahead of Print on October 6, 2008

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