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Citation: European Journal of Cancer Supplements, Vol 7 No 2, September 2009, Page 395
A. Santoro1, G. Citterio2, T. Pressiani1, V. Gregorc2, L. Rimassa1, F.G. De Braud3, G. Rossoni2, F. Caligaris Cappio2, A. Lambiase4, C. Bordignon4
1Istituto Clinico Humanitas, Department of Oncology, Milan, Italy
2Istituto Scientifico San Raffaele, Department of Oncology, Milan, Italy
3Istituto Europeo di Oncologia, Clinical Pharmacology and New Drugs, Milan, Italy
4MolMed, Clinical Development, Milan, Italy
Background: HCC is a highly vascularised tumor with a median survival of 6 months reported in untreated pts with advanced disease class C according to Barcelona Clinic Liver Cancer (BCLC) staging. NGR-hTNF is a VTA consisting of TNF-a fused to the tumor-homing peptide NGR, which binds an aminopeptidase N overexpressed on tumor vessels.
Methods: Advanced-stage HCC pts received NGR-hTNF 0.8 μg/m2 infused over 1-hour every 3 weeks (q3w). Progression-free survival (PFS) was the primary study aim with restaging performed q6w. A two-stage design was used with 16 and 27 pts to be enrolled. Subsequently, an additional 12 pts were treated with 0.8 μg/m2 on a weekly basis (weekly cohort).
Results: Pts with documented progression after loco-regional treatments (59%), systemic therapies (56%; range, 1–3 regimens), or both (33%) received 90 cycles (range, 1–18+). Pt characteristics were: median age 65 years (range, 34–79); M/F 21/6; PS 0/1 18/9; Child-Pugh (C-P) A/B 21/6, BCLC B/C 5/22. No grade 3–4 drug-related toxicities were observed. Main grade 1–2 toxicities were short-lived, infusion-related chills (55%). The median PFS was 2.3 months (95% CI, 1.7–2.9). The disease control rate (DCR) was 30% and the confirmed response rate was 8%. A complete response (4%) lasting 11.5+ months was observed in a 76-year-old sorafenib-refractory, C-P B pt. A partial response (4%) with a 78% tumor reduction was reported in a further C-P B pt. Additionally, a 28% tumor shrinkage was detected in one out of 6 patients (22%) experiencing stable disease. Pts who achieved disease control received a median of 5 cycles (range, 4–18+) and had a median PFS of 4.3 months (range, 3.0–12.8+). With a median follow-up of 14.0 months (95% CI, 12.7–15.3), 8 pts (30%) were still alive and the median overall survival (OS) time was 9.1 months (range, 1.3–21.3+). The survival rates at 12 and 18 months were 34% and 22%, respectively. In the weekly cohort, there was no worsening of toxicity and the DCR was 33%. The subset of 12 sorafenib-pretreated pts reported a response rate of 8% and a DCR of 33%, whereas the median PFS and OS were 2.3 and 9.5 months, respectively.
Conclusions: NGR-hTNF is well tolerated and appears to have promising antitumor activity in previously treated HCC patients. The drug will be further developed in this setting.
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