Dear Readers,
We are highlighting several key areas of clinical research in this issue of CCA News. The role of radiation therapy in locally advanced intrahepatic cholangiocarcinoma (iCCA) has been established in single-arm phase 2 trials; however, there is a lack of randomized controlled data.
The ABC-07 study led by Hawkins randomized biliary tract cancer (BTC) patients to either chemotherapy or consolidative stereotactic body radiotherapy (SBRT) after a course of induction chemotherapy. This phase 2 trial included BTC patients and reported on nonsignificant difference in progression-free survival (PFS) between the SBRT and chemotherapy-alone groups. However, there was a trend toward improved survival with radiotherapy. Notably, this study had a very small number of iCCA patients and heterogeneity could have affected the trial results.
The role of immunotherapy in the second-line setting after prior treatment with checkpoint inhibitors is currently unclear. Yoon and colleagues from Korea presented a phase 2 study of sitravatinib (multitargeted tyrosine kinase inhibitor) along with tislelizumab for advanced BTC who had been treated with prior chemo–immunotherapy. In this study of 43 patients, a 20% response rate and a PFS of 5 months were noted. Those patients who had a homologous recombination deficiency genotype appeared to have a better outcome with the combination. This raises intriguing possibilities of immune checkpoint inhibitor combinations in the second-line setting.
Erdafitinib is currently FDA approved for FGFR-altered bladder cancer. However, its role in cholangiocarcinoma (CCA) with FGFR2 genetic alterations has not been described. In the RAGNAR study, Pant and colleagues reported strong efficacy in 78 patients, the majority of whom had FGFR2 fusion with a response rate of approximately 55%. PFS noted was 8.5 months, indicating that this is a valid option for FGFR-altered CCA patients in the second-line or subsequent settings. HER2/neu-targeted therapies are a critical need in gallbladder cancer, and the DESTINY-PanTumor02 and HERIZON trials have indicated a positive signal, especially for HER2/neu 3+ gallbladder cancer with trastuzumab-deruxtecan and zanidatamab, respectively.
Nelitolimod, a TLR-9 agonist, was investigated as a hepatic arterial infusion by Lee and colleagues for iCCA and hepatocellular carcinoma in the PERIO-02 trial. This was a phase 1 study of escalating doses of the study agent with checkpoint inhibitors. Although responses occurred in a minority of patients, prolonged stable disease was noted, and the median overall survival ranged from 120 to 170 days, with immune effects including an increase in CD8/myeloid-derived suppressor cell ratio.
Heumann and colleagues presented a combination of atezolizumab along with varlilumab with or without the MEK inhibitor, cobimetinib, in the cohort of previously treated unresectable BTC. This study accrued in a rapid time course. Although the required threshold for response rate was not met, the treatment was generally tolerable and the combination with cobimetinib showed a nonsignificant improvement in PFS. These and other key areas of research are included in this September issue.
We look forward to seeing you all at the CCA Summit, October 17-19, 2024, at Hyatt Lost Pines, Bastrop, TX.
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