Key takeaways
- HCC treatment has moved beyond the TKI era, with immunotherapy-based regimens from IMbrave150, HIMALAYA, and CheckMate 9DW expanding first-line options.
- Biliary tract cancer now has immunotherapy-based first-line options after years in which gemcitabine-cisplatin remained the main standard, supported by TOPAZ-1 and KEYNOTE-966.
- Somatostatin analogs remain foundational in well-differentiated GEP-NETs, particularly for somatostatin receptor-positive disease, although responses are often disease stabilization rather than tumor shrinkage.
- PRRT has expanded the treatment landscape in NETs, with NETTER-1 and NETTER-2 supporting the role of lutetium-177 dotatate in selected patients.
- More options mean more sequencing decisions, and treatment should be individualized according to patient characteristics, safety, access, tumor burden, and clinical experience.
At the Community Oncology Global Congress (COGC 2026), organized by OncoDaily, Josué J. Bravo Espinoza, Medical Oncologist at Clínica Oncosalud, Auna, Peru, reviewed how treatment has evolved across hepatocellular carcinoma (HCC), biliary tract cancer, and gastroenteropancreatic neuroendocrine tumors (GEP-NETs).
Across all three disease groups, the therapeutic landscape has widened considerably. HCC has moved beyond a long period dominated by tyrosine kinase inhibitors. Immunotherapy has entered the first-line setting in biliary tract cancer after years of limited progress. And in neuroendocrine tumors, somatostatin analogs are now part of a broader sequence that includes peptide receptor radionuclide therapy (PRRT) and targeted therapy.
The challenge is increasingly less about whether another option exists and more about which option fits the patient in front of you.
HCC Moves Beyond the TKI Era
For years, sorafenib defined systemic treatment for advanced HCC. Bravo Espinoza focused on how immunotherapy-based regimens have changed that landscape.
The IMbrave150 trial established atezolizumab plus bevacizumab as a major first-line option, with updated results showing median overall survival of 19.2 months compared with 13.4 months with sorafenib and an objective response rate close to 30%.
“For a decade, we were using TKIs, but now we have the opportunity to introduce immuno-oncology. We have different options for our patients, and we have to choose according to the stage, the status of the patient, and also the status of liver function.”
The HIMALAYA trial added another approach through STRIDE – a single priming dose of tremelimumab combined with durvalumab. At five years, overall survival was 19.6% with STRIDE compared with 9.4% with sorafenib, reinforcing the possibility of durable benefit for a subset of patients.
Bravo Espinoza repeatedly returned to the importance of selection: longer survival has to be weighed against immune-related toxicity and the underlying condition of a liver that is often already compromised by chronic disease.
A third option came from CheckMate 9DW, which compared nivolumab plus ipilimumab with investigator’s choice of lenvatinib or sorafenib. Median overall survival was 23.7 versus 20.6 months, with response rates of 36.1% and 13.2%, respectively. The regimen received FDA approval for first-line unresectable or metastatic HCC in 2025.
Rather than producing one obvious treatment for every patient, these trials have created a different clinical problem: how to choose among several effective first-line strategies while accounting for liver function, comorbidities, toxicity, and individual patient characteristics.
After a Decade of Gemcitabine and Cisplatin
The shift in biliary tract cancer has been similarly significant.
For roughly a decade, the ABC-02 regimen of gemcitabine and cisplatin remained the reference first-line treatment, with few advances capable of meaningfully altering that standard.
“Between 10 years, we didn’t have any study or protocol positive. At this time, we have introduced immunotherapy. We have positive studies that we can use, adding to our tools for our patients.”
The TOPAZ-1 trial added durvalumab to gemcitabine and cisplatin. With longer follow-up, median overall survival was 12.9 months versus 11.3 months with chemotherapy alone, while the three-year survival rates were 14.6% and 6.9%, respectively.
For Bravo Espinoza, the tail of that survival curve was particularly meaningful. Biliary tract cancer is frequently diagnosed at an advanced stage, so seeing a population of longer-term survivors represented a change from the historical picture.
KEYNOTE-966 provided another immunotherapy-based option, with pembrolizumab plus gemcitabine and cisplatin improving median overall survival to 12.7 months compared with 10.9 months with chemotherapy alone.
The result is a first-line landscape that looks very different from the one oncologists had for much of the previous decade.
The question now is not whether immunotherapy belongs in advanced biliary tract cancer, but how clinicians choose between available regimens while considering patient characteristics, safety, access, and the evidence behind each approach.
In NETs, Disease Stabilization Is No Longer the Whole Story
Bravo Espinoza then turned to well-differentiated GEP-NETs, where treatment has expanded in a different direction.
Somatostatin analogs remain foundational therapy for appropriate somatostatin receptor-positive tumors, supported by studies such as PROMID and CLARINET.
But their benefit often appears primarily as disease control rather than dramatic tumor shrinkage.
“With the somatostatin analogs, most of them will have a low response rate. The main response will be stable disease.”
PRRT changed what could be expected in selected patients.
In NETTER-1, ^177Lu-DOTATATE plus octreotide produced a major progression-free survival benefit over high-dose octreotide in patients with progressive, somatostatin receptor-positive midgut NETs. Final median overall survival was 48.0 versus 36.3 months, although that secondary endpoint did not reach statistical significance, with crossover to subsequent radioligand therapy complicating interpretation.
More recently, NETTER-2 moved PRRT earlier by evaluating ^177Lu-DOTATATE in the first-line setting for higher-grade, well-differentiated advanced GEP-NETs. The trial reported a substantial improvement in progression-free survival and an objective response rate of 43% versus 9.3% with high-dose octreotide.
For Bravo Espinoza, that progression reflects how much the field has changed:
“From 2009 until 2026, now we have more options to offer to our patients. Before, the response was mainly stable disease. Now we are also seeing partial responses.”
More Options Mean More Sequencing Decisions
The CABINET trial added another important option for previously treated progressive NETs.
Cabozantinib significantly improved progression-free survival in both pancreatic and extra-pancreatic neuroendocrine tumors. In the published trial, median PFS was 13.8 versus 4.4 months in pancreatic NETs and 8.4 versus 3.9 months in extra-pancreatic NETs.
The FDA subsequently approved cabozantinib in 2025 for previously treated, unresectable, locally advanced or metastatic well-differentiated pancreatic and extra-pancreatic NETs.
That expanding toolbox makes sequencing increasingly important. Somatostatin analogs, PRRT, targeted treatments, and chemotherapy all have a place, but not necessarily for the same patient or at the same point in the disease course.
Bravo Espinoza emphasized that chemotherapy may still be particularly relevant when greater tumor burden or more aggressive disease requires a different treatment strategy.
And that brought his presentation back to the principle connecting all three malignancies:
“Treatment should be individualized based on patient characteristics, safety profile, access and clinical experience.”
HCC, biliary tract cancer, and GEP-NETs now offer clinicians substantially more therapeutic possibilities than they did a decade ago.
The progress is clear. The harder part now is choosing and sequencing those options well.
Written by Eliz Baloyan, MD, Features Writer and Editor at OncoDaily and CancerWorld
