Anti–PD-1 Therapy Likely Leads to Responses in Advanced ICC

The therapy for intrahepatic cholangiocarcinoma (ICC) led to responses in about a quarter of patients and disease control in 85%.

A new retrospective analysis of real-world intrahepatic cholangiocarcinoma (ICC) outcomes suggests anti–programmed cell death protein-1 (anti–PD-1) therapies can be a meaningful treatment option.

The report, published in Annals of Medicine, is based on a single-center retrospective analysis of advanced cases of ICC. The study authors noted that people with ICC face a poor prognosis and that most are not candidates for curative resection.

“Especially for patients with advanced ICC, few effective therapies can improve the clinical prognosis,” they said. “Consequently, more efficient treatments are urgently needed for ICC patients.”

In other malignancies, immune checkpoint inhibitors (ICIs) targeting PD-1 and programmed death-ligand 1 (PD-L1) have shown promise. Yet, the investigators said ICIs “are still rarely applied” to ICC and there is no clear data as to the therapies’ efficacy in real-world scenarios. “Noticeably, immunotherapy seems to have therapeutic prospects in biliary tract cancer, but more studies are needed to confirm it,” they wrote.

In the new study, they retrospectively analyzed the cases of 42 people with advanced ICC who were treated with anti–PD-1 therapies between August 2018 and December 2020. The patients were followed for a median of 12.1 months, and their median time of treatment was 6.7 months.

The investigators calculated an overall response rate of 23.8% and a disease control rate of 85.7%. For the entire cohort, the median overall survival was 19.3 months and the median progression-free survival and time to tumor progression were 11.6 months each.

“Our single-center retrospective study proved that PD-1–targeted immunotherapy exhibited promising efficacy and slight toxicity in a real-world cohort of patients with advanced ICC,” the authors wrote.

Pain (6 cases) was the most common adverse event, followed by anorexia and hypertension (4 cases each). Pyrexia, cough, and hypothyroidism were reported in 3 cases each.

The authors noted that outcomes varied based on liver function, as patients with albumin-bilirubin grade 2 cases had somewhat shorter median OS compared with those classified as albumin-bilirubin grade 1 (14.7 vs 19.3 months). They said that although their study adds important real-world information to the question of whether ICIs are a useful treatment for patients with ICC, it still leaves several questions.

For example, they said their sample size was not sufficient to make comparisons between different ICIs. In addition, the patients in this study did not undergo genetic testing.

“Since it is a trend to combine molecular markers to predict efficacy, molecular markers may better indicate the efficacy of immune or targeted therapy and suggest more suitable combination therapies,” they wrote, adding that additional studies should look at whether ICIs should be paired with other types of therapy, dubbing that question a “hot spot worthy of attention.”

Despite those limitations, the investigators said their experience shows that anti–PD-1 immunotherapy can lead to meaningful responses in a patient area with a significant unmet need.

“In conclusion, PD-1–targeted immunotherapy is a safe and effective treatment for advanced ICC patients and provides another therapeutic strategy for these patients,” they said.


Deng M, Li S, Wang Q, et al. Real-world outcomes of patients with advanced intrahepatic cholangiocarcinoma treated with programmed cell death protein-1-targeted immunotherapy. Ann Med. 2022;54(1):803-811. doi:10.1080/07853890.2022.2048416