High-dose interleukin-2 (HD-IL2) can be effective in selected patients with metastatic renal cell carcinoma (mRCC) pretreated with VEGF-targeted agents, according to research presented at the European Society for Medical Oncology Symposium on Immuno-Oncology 2014, in Geneva, Switzerland.

“Despite the wide and increasing range of therapies available, the management of metastatic renal cell carcinoma remains challenging. Agents targeting the vascular endothelial growth factor (VEGF) and mammalian target of rapamycin (mTOR) pathways are currently the standard of care,” said lead author Dr. Manon Evans, research fellow at the Christie Hospital in Manchester, United Kingdom. “Whilst these therapies are well tolerated and demonstrate impressive response rates, the responses seen are very rarely complete and durable.”

“High-dose interleukin-2 (HD-IL2)—a protein that activates the immune system—can induce durable complete responses in small numbers of patients with mRCC. However, due to significant toxicities, its use remains limited. To date, it has been used as an option in the treatment-naïve population only, with concerns over its efficacy and safety post-VEGF targeted agents.”

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The current study is a retrospective analysis of 180 patients treated with HD-IL2 at the Christie NHS Foundation Trust over the past 10 years. The majority were treated in the first-line setting, with a smaller cohort receiving treatment following VEGF-targeted agents. The researchers also investigated whether expression of the biomarker carbonic anhydrase IX (CAIX) correlated with outcome and could potentially be added to the selection criteria for HD-IL2 therapy.

A total of 180 patients with mRCC were treated with HD-IL2, 145 in the treatment-naïve cohort, and 35 in the pretreated cohort. Of these, a total of 158 had favorable histology, more than 45% responded with a 23% complete remission rate. Of those achieving a complete response to therapy, more than 75% are alive and disease free. The median overall survival in those achieving a complete response has not yet been reached. There was no significant difference in response or survival rate between the two treatment cohorts.

CAIX positivity correlated favorably with response and survival as did disease burden and tolerance of treatment. All patients experienced toxicity as anticipated. The incidence of treatment-related myocarditis was higher in the pretreated cohort (8.5%) compared to the treatment-naïve group (3.4%).

“Our data confirms that there remains a role for HD-IL2 in the management of mRCC and demonstrates, in a selected population, complete responses [in more than] 20%, most of which are durable. In contrast to initial reports, it can be safe and effective in carefully selected patients pretreated with VEGF-targeted agents with response rates and complete responses similar to first-line therapy. Its application should strongly be considered in both the treatment-naïve and pretreated population,” said Evans.

“Outcomes were clearly superior in patients with favorable histology (incorporating those with solid/alveolar clear cell RCC) but there were rare durable complete remissions in patients with other histologies and the role of HD-IL2 in this group is less well defined with further assessment required.”

A video interview with Prof. John Haanen, Head of Division of Medical Oncology at NKI-AVL, Amsterdam, The Netherlands, may be viewed here