502 - Association between peripheral blood lymphocyte count (PBLC) and outcome in patients with solid tumors treated with NGR-HTNF
|Date||28 September 2012|
|Event||ESMO Congress 2012|
|Topics|| Translational Research
A. Bulotta1, V. Gregorc2, G.M. Rossoni1, G. Todisco2, M.G. Viganò2, A. Lambiase3, C. Bordignon3
NGR-hTNF (asn-gly-arg-human tumor necrosis factor) induces antitumor effects by selectively damaging tumor neovasculature and increasing intratumoral infiltration of effector T cells. We investigated whether pretreatment PBLC values were associated with treatment outcomes in 5 phase II single-arm trials on 205 patients (pts) who were refractory/resistant to standard therapies.Methods
NGR-hTNF 0.8 µg/m2 was given every 3 weeks (q3w) alone in pts with malignant pleural mesothelioma (MPM n = 55), hepatocellular carcinoma (HCC n = 40), and colorectal cancer (CRC n = 45), or combined with doxorubicin in small-cell lung cancer (SCLC n = 28) and ovarian cancer (OC n = 37). Tumor assessment by RECIST was done q6w until progression. Kaplan-Meier methods and Cox models were used to determine univariate and multivariate associations between baseline PBLC and progression-free survival (PFS) and overall survival (OS).Results
Median baseline PBLC value was 1.4/mL (range 0.3-6.9; interquartile range 1.0-1.8) in 198 pts with available pretreatment counts. The first distribution quartile was used as cut-off value to dichotomize PBLC into high (≥ 1.0; n = 144, 73%) or low (< 1.0; n = 54, 27%) levels. Baseline characteristics (high v low levels): median age 65 v 65; male 51% v 52%; PS 1-2 31% v 39%, range of prior treatment lines 1-5 v 1-5. Mean number of cycles was 4.5 (range 1-24) in pts with high and 3.3 (1-13) in pts with low levels (p = .02). In univariate analyses, pts with high PBLC had significantly improved PFS (HR = 0.68 p = .02) and OS (HR = 0.51 p = .0001). Six-month PFS rates were 21% (95% CI 14-28) in the high and 9% (1-17) in the low PBLC groups (log-rank p = .02), while 1-year OS was 52% (44-60) in pts with high and 28% (16-40) in pts with low levels (p = .0001). After adjusting for major baseline factors (age, gender, PS, prior lines, and tumor type), a high PBLC remained independent predictor of longer PFS (HR = 0.60 p = .01) and OS (HR = 0.52 p = .0003). Median OS in pts stratified by PBLC < 1.0/mL, 1.0 to 1.8/mL, and > 1.8/mL were 7.7, 9.1, and 16.7 months, respectively (p < .0001 for trend).Conclusions
Pretreatment PBLC value may be used to identify which patients are likely to gain treatment benefit from NGR-hTNF.Disclosure
C. Bordignon: Employment - MolMed.
All other authors have declared no conflicts of interest.