EVALUATING THE PLACE OF INTERLEUKIN-2 IN THE MANAGEMENT OF METASTATIC RENAL CELL CANCER (MRCC) IN THE ERA OF TARGETED THERAPY

Annals of Oncology(2014)

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ABSTRACT Introduction Despite the advent of targeted agents for the treatment of mRCC, HD-IL2 is the only licensed agent consistently capable of achieving durable long term remissions. Its role in treatment-naive patients is well recognised but its efficacy and feasibility after VEGF-targeted therapies is less certain. We present outcomes from our experience of HD-IL2 therapy in both treatment-naive (Group A) and patients pre-treated with VEGF-targeted therapies (Group B). Methods We provide a regional/national treatment service with HD-IL2 for selected patients with mRCC. Selection is based on clinical and histological features as described by Shablak (Shablak et al., J Immunother. 2011; 34(1):107-12). 180 patients were analysed with 145 in Group A (treated 2003-2013) and 35 in Group B (treated 2007-2013). HD-IL2 was administered as per standard dosing and schedule. Clinical records were reviewed retrospectively; survivals were analysed by Kaplan-Meir methods. Results The majority of patients had ‘Favourable’ histology with 89% in Group A and 88% in Group B. As previously reported the outcomes were clearly superior in those with favourable histology but there were rare durable complete remissions in patients with other histologies. Outcomes in patients with ‘Favourable’ histology were comparable in both populations with overall response rates (ORR) and complete response (CR) rates being 47%,23% (Group A) and 42% 19% (Group B). Most CRs are durable and Median OS in CR patients is not yet reached in either group. All patients experienced expected toxicities associated with treatment. 8 (5.5%) (Group A) and 2 (5.7%)(Group B) of patients were transferred to critical care for invasive monitoring. 5 (3.4%) patients in the treatment-naive group developed myocarditis vs 3 (8.5%) in the pre-treated group – with one treatment related death in (related to myocarditis). Conclusions Our results confirm that HD-IL2 remains an effective first-line treatment in well-selected patients with mRCC providing durable complete remissions in over 20% of patients. While cardiac toxicity appears higher in pre-treated patients, HD-IL2 in this setting is effective, tolerable and can produce durable remissions comparable to those seen in the first-line setting. With the introduction of increasing numbers of therapies (including new immune therapies) for the treatment of mRCC it is important to make the best use of all treatments and to combine / sequence therapies to maximise the chance of durable benefits for patients. Disclosure All authors have declared no conflicts of interest.
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