1950P - TRANSLATE: Activation of immune response in refractory patients to standard treatment

Background

The TRANSLATE exploratory study tests changes of cytokines over treatment with metronomic cyclophosphamide, daily low dose of IL-2 every other week, and 8 Gy single fraction RT (self vaccination) in end-stage solid tumors.

Methods

Patients with end stage tumors with no further standard treatment available were eligible. A panel of 17 cytokines was analysed. Plasma concentrations were assessed at baseline (T0), day 8 (after RT) (T1), day 28 (T2), and at disease progression (PD) (T3), using Simple Plexsystem (ProteinSimple, USA). Patients were divided in two groups depending on the time of PFS (group A<3 months, group B>3 months). Values at each time points were compared and correlated to outcome. P<0.05 was considered for statistical significance.

Results

23 patients with breast, colon, kidney and prostate cancer were enrolled. IL-2 progressively increased from T0 to T2 (T_0-2 P<0.001; T_1-2 P=0.002) and decreased at T3. IL-5 progressively increased from T0 to T2 (T_0-2 P=0.005; T_1-2 P=0.049) and decreased at T3 (T_2-3 P=0.048). IL-8 remained stable along the treatment but increased at T3 (T_0-3 P=0.057; T_1-3 P=0.022; T_2-3 P=0.018). CCL-4 decreased from T1 to T2 (P=0.040) but increased at T3 (P=0.008). IFN-γ progressively decreased from T1 to T3 (T_1-3 P=0.026; T_2-3 P=0.034). VEGF performance differed between group A and B: while it remained stable in group B, increased from T0 to T1 in group A. However, considering all together, VEGF increased at T3 compared to T0 (T_0-3 P=0.022). Using ROC analysis at T0 we identified cut-off values for IL-2, IL-12, and CCL-2. Using them, we observed a significant improvement in PFS in patients with values of IL-2 and IL-12 higher than their respective cut-offs and with CCL-2 lower than its cut-off (HR 0.33, P=0.03; HR 0.32, P=0.029; HR 0.37, P=0.049; respectively). We performed a multivariate analysis coupling these three cytokines two by two. Only IL-2 and CCL-2 remained associated with PFS.

Conclusions

The small number of patients limits the interpretation of our results. However, our data suggest that IL-2 and CCL-2 might predict good and poor PFS respectively.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.