Tremelimumab plus TACE, RFA, or Cryoablation in Hepatocellular Carcinoma or Biliary Tract Carcinoma
Tremelimumab is a fully human monoclonal antibody that binds to CTLA-4 expressed on the surface of activated T lymphocytes and results in inhibition of B7-CTLA-4â€“mediated downregulation of T-cell activation, and has previously been shown to be safe in patients with hepatocellular carcinoma (HCC) when administered as a single agent.1 Transcatheter arterial chemoembolization (TACE), radiofrequency ablation (RFA), and cryoablation (CA) have been shown to induce a peripheral immune response that may enhance the effect of antiâ€“CTLA-4 treatment in patients with advanced hepatocellular carcinoma (HCC). In a presentation by Duffy and colleagues, patients with HCC [Childs Pugh A/B7; BCLC B/C; ECOG 0/1; post-sorafenib (BCLC stage C only)] or refractory biliary tract carcinoma (BTC) were enrolled in a study of tremelimumab combined with subtotal TACE, RFA, or CA performed on week 6.2 All BTC patients received RFA as the immunostimulant in combination with tremelimumab.
A total of 41 patients have been treated so far (32 HCC, 9 BTC) in the trial; of the HCC patients, 14 patients received TACE, 10 underwent RFA, and 5 underwent CA, all during week 6 of tremelimumab therapy. Two patients did not receive an ablative procedure. No dose-limiting toxicities were encountered, with the most common adverse event being pruritus. One patient developed pulmonitis and was taken off study but remained disease-free at 16 months. Of 31 patients evaluable for response outside of TACE/RFA-treated lesion, 5 (16%) achieved a confirmed partial responses, and 12 (39%) had stable disease; 8 of 9 patients with quantifiable HCV experienced a marked reduction in viral load. The 6-week tumor biopsies showed immune cell infiltration on all evaluable patients. Median progression-free survival for the evaluable HCC population (N = 25) was 5.7 months. The authors concluded that tremelimumab in combination with subtotal TACE, RFA, or CA in patients with advanced HCC and BTC is safe and feasible, with encouraging clinical activity observed in HCC.
- Sangro B, et al. J Hepatol. 2013;59:81-8.
- Duffy AG, et al. ASCO 2016 Gastrointestinal Cancers Symposium. Abstract 270.