No difference in survival between combination and single therapy in renal cell carcinoma, but some patients could benefit from combination therapy

Combination therapy for renal cell carcinoma does not improve overall or progression-free survival compared with single therapy using interferon alfa-2a alone. However, the combined regimen might still have a role because it can produce remissions that are of clinically relevant length in some patients. Thus identification of these patients is crucial. These are the conclusions of an article published in an upcoming edition of The Lancet, written by Professor Martin E Gore, Department of Medicine, Royal Marsden Hospital NHS Trust, London, and colleagues.

Renal cell carcinomas account for 2% of all malignant tumours in adults. 30% of patients with renal cell carcinoma present with metastatic disease (secondary tumours), and half of those who apparently have localised disease at diagnosis subsequently develop metastases. Median survival for patients with advanced disease is 10 months and 5-year survival is 15%. The immunotherapy regimen that has been associated with the highest response rates in metastatic renal cell carcinoma is a combination of interferon alfa-2a, interleukin-2, and fluorouracil. In this study, the authors compared interferon alfa-2a alone—with combined interferon alfa-2a, interleukin-2, and fluorouracil.

This randomised trial was undertaken in 50 centres across eight countries. 1006 treatment-naive patients diagnosed with advanced metastatic renal cell carcinoma were assigned to receive interferon alfa-2a alone or combination therapy with interferon alfa-2a, interleukin-2, and fluorouracil. The primary endpoint was overall survival.

A total of 502 patients were randomly assigned to receive interferon alfa-2a and 504 to receive combined treatment. Median follow-up was just over three years. Median overall survival was 18·8 months for patients receiving interferon alfa-2a versus 18·6 months for those receiving combination therapy. Overall survival did not differ between the two groups. Serious adverse events were reported in 113 (23%) patients receiving interferon alfa-2a and 131 (26%) of those receiving combined treatment.

Professor Gore says: “Although combination therapy does not improve overall or progression-free survival compared with interferon alfa-2a alone, immunotherapy might still have a role because it can produce long remissions in a small number of patients. Identification of these patients is of considerable importance.”

He adds: “The individualisation of cancer therapies based on identifying predictive markers within tumours is important. This particularly applies to immunotherapy for kidney cancer where there can be considerable benefit but only for a small percentage of patients.”


Source: The Lancet