Adjuvant therapy may benefit subsets of renal cell carcinoma patients

Chicago-Adjuvant immunotherapy with interleukin-2 (IL-2) plus interferon-alpha offers no survival advantage to the overall population of patients with resected renal cell carcinoma, but may benefit selected subgroups of patients, results of a randomized, multicenter clinical trial indicate.

"These factors can be considered predictive of benefit from adjuvant IL-2 and interferon-alpha," said Rodolfo Passalacqua, MD, an oncologist at Cremona Hospital in Cremona, Italy. "In the presence of two or more factors, adjuvant immunotherapy gives a significant reduction of recurrences. However, in the absence of these factors, adjuvant immunotherapy has a detrimental effect."

Low-dose IL-2 induces expansion of human natural killer cells and T-lymphocytes, and the combination of low-dose IL-2 and interferon-alpha has demonstrated activity in metastatic RCC. In limited clinical evaluation, the combination has led to response rates of 12% to 20% and median survival of 15 to 24 months. The results include data from a randomized trial of the combination as first-line therapy for metastatic cancer, which Dr. Passalacqua reported at the 2003 ASCO annual meeting.

The experimental regimen consisted of IL-2 administered subcutaneously at a dose of 1 million IU/m² twice daily on days 1 and 2 followed by 1 million IU/m² on days 3 to 5 plus interferon-alpha, 1.8M IU/m² , on days 3 and 5. The therapy was repeated weekly for 4 weeks, then every 4 months for 2 years, and every 6 months thereafter.

The primary endpoints of the trial were recurrence-free survival and overall survival. Secondary clinical objectives were tolerability, toxicity, and safety of the adjuvant therapy.

No significant differences

About 60% of patients in each group had stage T1-2 disease, unknown nodal status, and grade 1-2 cancer. More than 90% of patients had a radical nephrectomy, and 60% to 65% of the patients were judged to be intermediate risk by UCLA Integrated Staging System criteria.

After a median follow-up of 52 months, the two patient groups did not differ with respect to recurrence-free or overall survival. Survival curves were superimposable for approximately 5 years and then appeared to separate, resulting in a nonsignificant hazard ratio of 0.81 for the immunotherapy group. A similar pattern emerged with respect to overall survival, except the curves remained superimposed beyond 10 years. The hazard ratio of 1.07 was not significant.

An exploratory analysis of clinical and demographic variables suggested the experimental regimen might be beneficial for four patient subsets that fared better than others. Recalculation of recurrence-free survival suggested much greater benefits of adjuvant therapy in patients with those characteristics.

When Dr. Passalacqua and colleagues compared patients with two or more predictive factors versus fewer, they found a statistically significant improvement in the hazard ratio for recurrence-free survival of almost 60% with the adjuvant therapy (p<.01). In contrast, patients with fewer than two of the prognostically favorable features seemed to fare worse with the adjuvant immunotherapy, as reflected by a hazard ratio of 1.81.

"Further studies are needed to confirm these observations," Dr. Passalacqua concluded.