Atezolizumab/Bevacizumab Shown Effective Against CHC

The combination is approved to treat hepatocellular carcinoma (HCC), but this case report suggests it can also work for combined HCC and cholangiocarcinoma (CHC).

A new case report suggests that an immunotherapy combination for hepatocellular carcinoma (HCC) might also be effective in patients who have combined HCC and cholangiocarcinoma (CHC).

CHC is a rare liver cancer with features of HCC and cholangiocarcinoma. Patients with this diagnosis can potentially undergo surgical resection, but recurrence is common, often with metastatic disease.

Tecentriq (atezolizumab) is an anti–programmed death ligand-1 (PD-L1) agent, and Avastin (bevacizumab) is a humanized anti–vascular endothelial growth factor monoclonal antibody. This combination is approved by the FDA to treat patients with HCC. However, it is unclear whether the combination might also be effective against CHC.

In a new article published in Clinical Case Reports, a team from Japan’s Gunma Saiseikai Maebashi Hospital, describe the case of an 81-year-old man with diagnosed CHC who was successfully treated with atezolizumab and bevacizumab. The patient was initially referred to the hospital for liver tumor removal. Post resection, an examination of the tumor revealed elements of HCC and cholangiocarcinoma. Both regions were negative for PD-L1, and microsatellite instability status was negative. The investigators also found evidence of alcoholic liver disease.

The patient underwent adjuvant chemotherapy, but 13 months after surgery doctors found evidence of multiple lymph node metastases on enhanced CT. He was then put on systemic chemotherapy with Gemzar (gemcitabine) and Platinol (cisplatin), but the therapy had to be discontinued because of severe rash.

Next, doctors tried Lenvima (lenvatinib), which was the recommended first-line treatment for HCC at the time. However, the patient experienced grade 3 decreased appetite, prompting clinicians to discontinue that therapy.

The investigators turned to their institutional review board, and after getting patient consent, they were authorized to try atezolizumab and bevacizumab. After two 3-week cycles, CT showed mild shrinkage of the enlarged lymph nodes and otherwise stable disease. Bevacizumab was interrupted over the next 3 cycles due to the presence of ascites. After 5 cycles, CT revealed a lasting tumor response. Bevacizumab was resumed on the sixth cycle, and the patient’s disease was deemed stable after 7 cycles.

Adverse events forced a second interruption of bevacizumab for the eighth and ninth cycles, and after 10 cycles, CT showed evidence of progressive disease. Overall, the patient experienced a progression-free survival of 7.5 months, a period of time comparable to that seen in previous studies of gemcitabine plus a platinum-based regimen. Fifteen months following the start of systemic therapy, the patient remained alive.

The investigators said these results, plus a limited amount of other published literature on the subject, suggest that hepatic-directed therapies might be a viable option in cases of unresectable CHC or in cases of recurrence following resection.

They said their study’s generalizability is limited because it is a single case report. In addition, they noted that immune checkpoint inhibitors have not been thoroughly studied in biliary tract malignant tumors, and it was not clear in this case whether the features of HCC or cholangiocarcinoma were dominant. Thus, they said it is not yet known whether the therapeutic regimen will be equally successful in all cases of CHC.

Reference

Saito N, Hatanaka T, Nakano S, et al. A case of unresectable combined hepatocellular and cholangiocarcinoma treated with atezolizumab plus bevacizumab. Clin Case Rep. Published online July 25, 2022. doi:10.1002/ccr3.6129