Prolonged Disease Stability with Durvalumab and Tremelimumab Rechallenge Following Prior Immune Checkpoint Inhibitors: A Case Report.

Background: Hepatocellular carcinoma (HCC) is the most common primary liver malignancy and remains a leading cause of cancer-related mortality worldwide due to frequent recurrence and early metastasis. While immune checkpoint inhibitor (ICPI)-based regimens have revolutionized the treatment landscape for advanced HCC, clinical evidence regarding the safety and efficacy of ICPI rechallenge following disease progression or severe immune-related adverse events (irAEs) remains sparse. This report describes a case of prolonged disease stability achieved through sequential immunotherapy using durvalumab and tremelimumab (Durva/Treme) after prior ICPI failure and high-grade toxicity. Case Description: A 65-year-old male with recurrent stage IV HCC and metastases to the adrenal glands and vertebral column was referred to our center after failing multiple lines of therapy, including atezolizumab/bevacizumab, sorafenib, and cabozantinib. Subsequent treatment with nivolumab plus ipilimumab was complicated by grade 3/4 immune-related hepatitis, necessitating a treatment hold and steroid intervention. Despite an initial response in hepatic lesions, imaging confirmed progression in the adrenal metastases. The patient was then transitioned to a rechallenge protocol with the STRIDE regimen (Durva/Treme). The patient completed 39 cycles of therapy over more than three years. Serial imaging demonstrated sustained stable disease (SD), and a significant reduction in alpha-fetoprotein (AFP) levels initially declined substantially during nivolumab/ipilimumab (Nivo/Ipi) therapy, rebounded prior to Durva/Treme initiation, and subsequently stabilized near baseline levels during ongoing Durva/Treme treatment. Notably, the rechallenge was well-tolerated with no recurrence of high-grade hepatotoxicity. Conclusions: This case demonstrates that ICPI rechallenge with Durva/Treme may provide durable disease control in selected patients with advanced HCC, even those with a history of severe immune-related toxicity. While the localized response was likely augmented by interval radiotherapy, the overall clinical course suggests that the STRIDE regimen may offer a feasible sequential immunotherapy option. These findings warrant further prospective investigation into the biological mechanisms of immune re-priming and the safety of immunotherapy sequencing in advanced oncology.