Triplet Regimen With Durvalumab May Increase Overall Survival of Patients with Fatal Intrahepatic Cholangiocarcinoma

Promising data suggest triplet regimens may more effectively treat patients with unresected and metastatic intrahepatic cholangiocarcinoma.

In a recent review, researchers looked at intrahepatic cholangiocarcinoma (ICC) treatment strategies, both current and future, and found that durvalumab and standard cytotoxic therapy may improve survival of patients with ICC. Further, different triplet regimens and immunotherapy may increase survival in patients with unresectable forms of the cancer.

“For the past decade, doublet chemotherapy with gemcitabine and cisplatin has been considered the most effective first-line regimen, but results from the recent use of triplet regimens and even immunotherapy may shift the paradigm,” the study authors wrote in a report published in CMS Journals.

ICC is the number 2 common primary type of liver cancer, and occurrence has increased more than 140% in the past 40 years. The deadly cancer, which has a 5-year overall survival (OS) rate of 9%, accounts for 20% of hepatic malignancies and 3% of gastrointestinal malignancies. The only cure for ICC is complete surgical resection, and it is only a cure for the 20%-30% of patients who have the resectable form of the disease.

“For patients with localized and resectable ICC, margin-negative hepatic resection and lymphadenectomy followed by adjuvant capecitabine should be considered the standard of care,” the study authors wrote.

But among patients with advanced and unresectable ICC, gemcitabine (Gem) and cisplatin (Cis) are the standard first-line treatment. In previous trials, the efficacy of triplet regimens with Gem/Cis has shown mixed results. These trials looked at the standard procedure for care on locally unresectable or metastatic biliary tract cancers, which includes the subtype ICC.

In a single-arm phase 2 trial, researchers added nab-paclitaxel to Gem/Cis in the first line setting. The results were promising, showing that median OS increased to 19.2 months in 44% of ICC subgroup patients. The trial displayed “remarkably better results” than traditional doublet regimens.

But durvalumab may have the most potential at improving ICC treatment efficacy and lifespan of patients. Durvalumab was studied in the TOPAZ-1 trial, a phase 3, randomized, double-blind, placebo-controlled study. Patients who took Gem/Cis with durvalumab had an OS that was 1.3 months longer than patients on standard Gem/Cis. The small median increase is not without large impact.

“The tail on the survival curves is encouraging, suggesting that up to 25% of patients were alive at 2 years and may see durable responses that are unprecedented with cytotoxic therapy,” the study authors wrote.

Cancer type, age, performance status, and underlying liver health should all be considered when creating an ICC management strategy. Current treatment options include surgical resection, perioperative chemotherapy, liver-directed therapies, transplantation, and systemic therapies, such as cytotoxic therapy, targeted therapy, and/or immunotherapy.

“In patients with unresectable or metastatic ICC, advancements, including…targeted therapy and immunotherapy [,] are now being increasingly used and have led to encouraging outcomes in optimally selected patients,” the investigators concluded.

Reference

Moris, Dimitrios, Palta, Manisha, Kim, Charles, et al. Advances in the treatment of intrahepatic cholangiocarcinoma: An overview of the current and future therapeutic landscape for clinicians. ACS Journals. October 19, 2022.https://doi.org/10.3322/caac.21759