Durvalumab and Tremelimumab Plus Ablative Therapy Disappoints Among Patients With Liver-Predominant Metastatic Colorectal Cancer

According to results from the phase 2 EORTC 1560 trial, durvalumab and tremelimumab plus liver-directed partial local ablative treatment did not lead to radiological response in untreated metastases among patients with liver-predominant metastatic colorectal cancer (mCRC). 

“Treatment strategies for mCRC patients with unresectable liver metastases include systemic therapy and local ablative treatments,” stated Jenny Seligmann, MD, PhD, St James’s Hospital, Leeds, United Kingdom, and coauthors. “While immunotherapy outcomes in patients with microsatellite stable mCRC have been disappointing, [local ablative treatments] may induce local immune activation and potentially prime the tumor microenvironment for a systemic immunotherapy response.” 

In this open-label study, researchers enrolled 20 patients with unresectable, liver-predominant mCRC with stable disease after completion of 3 to 6 months of first- or second-line chemotherapy. Patients received 1500 mg of durvalumab plus 75 mg of tremelimumab once every 4 weeks for up to 4 cycles followed by durvalumab alone for up to 8 months with either radiofrequency ablation (n = 12) or stereotactic body radiotherapy (n = 8). The primary end point was objective response rate (ORR) in untreated lesions. Key secondary end points included progression-free survival (PFS), overall survival (OS), and safety. 

At analysis, ORR was not achieved in untreated lesions. The best response was stable disease in 45% of patients and disease progression in 55% of patients. The median PFS was 2.2 months overall, with a median PFS of 2.2 months among patients who received radiofrequency ablation and 2.8 months among patients who received stereotactic body radiotherapy. The median OS was 16.1 months overall, with a median OS of 14.1 months among patients who received radiofrequency ablation and 16.1 months among patients who received stereotactic body radiotherapy. With a median follow-up duration of 17.1 months, 55% of patients died. The most frequent cause of death was disease progression (81.8%). 

Dr Seligmann et al, concluded,  “These findings highlight the urgent need for alternative therapeutic strategies for this patient population… [and] further studies should prioritize immunotherapeutic approaches guided by tumor location, novel agents, and biomarker-driven patient selection to enhance treatment response in this challenging clinical setting.” 

Source:

Seligmann J, Koessler T, Mauer M, et al. Durvalumab and tremelimumab plus local partial tumour ablation (radiofrequency ablation or stereotactic radiotherapy) in patients with unresectable liver metastases from metastatic colorectal cancer: Results of the EORTC-1560-GITCG multicentre, single-arm phase II study (ILOC). ESMO Open. Published online: July 23, 2025. doi: 10.1016/j.esmoop.2025.105508