Page 186 - Read Online

Gim et al. Hepatoma Res 2023;9:51 https://dx.doi.org/10.20517/2394-5079.2023.90 Page 15 of 20

[118]
based on current data, hepatic resection with negative margins is considered the preferred surgical goal .
The available research data on neoadjuvant and adjuvant chemotherapy in resectable iCCA presents
challenges in drawing definitive conclusions. A study result by Buettner et al. showed similar OS and PFS
between patients with perioperative chemotherapy and those without, although this needs to be cautiously
interpreted due to low neoadjuvant treatment patient numbers and possible selection bias effect .
[119]
Conversely, more recent research indicates that neoadjuvant therapy, particularly in stage II-III disease, may
lead to enhanced OS [120-122] . Moreover, the optimal adjuvant treatment strategy for resected iCCA remains
uncertain due to limited clinical trial data supporting a standard regimen.

The efficacy of targeted therapy as neoadjuvant or adjuvant treatment for resectable disease remains an
unexplored area of research. The challenges of limited early-stage detections and infrequent actionable
mutations hinder the conduct of studies in this domain. Moreover, the effects of targeted therapy on tumor
downstaging, survival benefits, recurrence-free survival, and potential adverse events leading to unfavorable
outcomes require further elucidation.

In an attempt to address this, a clinical trial (NCT05514912) is underway to evaluate chemo-targeted
therapy for resectable intrahepatic cholangiocarcinoma using infigratinib in combination with
chemotherapy in FGFR2 fusion-positive iCCA . The study aims to provide valuable insights into the
[123]
treatment efficacy for this specific patient subset. To our knowledge, there are currently no ongoing clinical
trials investigating the efficacy of targeted therapy or combination treatments with targeted therapy in an
adjuvant setting. Additional research is needed to address these uncertainties and shed light on potential
treatment strategies.

CONCLUSION
In summary, iCCA remains a formidable challenge with historically poor outcomes. However, recent
advancements in targeted therapies and immunotherapy offer hope for improved treatment strategies and
better patient outcomes.

Targeted therapies, such as FGFR inhibitors, IDH inhibitors, and HER2 inhibitors, are demonstrating
promising results in iCCA treatment by specifically targeting genetic alterations. These therapies provide
personalized treatments, offering the potential for more effective responses and increased survival rates
among iCCA patients.

Immunotherapies, including PD-L1 inhibitors and CAR T-cell therapy, have garnered significant attention
as emerging treatment modalities in the context of BTC. Numerous ongoing research endeavors are focused
on these approaches. Immune checkpoint inhibitors have gained FDA approvals for iCCA with TMB-H
and MSI-H/dMMR, expanding the therapeutic options available for advanced or metastatic disease.

Despite these breakthroughs, challenges such as conducting large trials, overcoming acquired resistance,
and optimizing treatment sequencing remain. Addressing these areas requires ongoing research and
investigation. In conclusion, while iCCA treatment remains challenging, recent progress in targeted
therapies and immunotherapy brings optimism. By advancing scientific understanding and clinical practice,
we can pave the way for better outcomes for iCCA patients.

DECLARATIONS
Acknowledgments
I would like to acknowledge Donghyun Gim for providing assistance with creating the figure.