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
Session Publication Only
Topics Translational Research
Presenter Alessandra Bulotta
Authors A. Bulotta1, V. Gregorc2, G.M. Rossoni1, G. Todisco2, M.G. Viganò2, A. Lambiase3, C. Bordignon3
  • 1IRCCS San Raffaele, IT-20132 - Milano/IT
  • 2Oncologia, IRCCS San Raffaele, IT-20132 - Milano/IT
  • 3Clinical Development, MolMed, 20132 - Milan/IT

Abstract

Background

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.