Biliary Tract and Gallbladder Cancer Landmark Atlas

What did the researchers want to learn?

In biliary tract or gallbladder cancer removed by surgery, does oral capecitabine prolong survival?

What did this study change?

Adjuvant capecitabine became an option in suitable patients; the ITT uncertainty is stated openly.

Benefit for patients

Relevant to the adjuvant capecitabine decision in surgically removed biliary tract cancer.

What did the research find?

The primary intention-to-treat (ITT) analysis did not reach statistical significance; per-protocol, sensitivity and long-term analyses provide support in favor of capecitabine. ITT / per-protocol (PP) / sensitivity analyses are read separately.

Who does this apply to?

The same benefit in all patients, or superiority over all other adjuvant treatments, has not been proven. The gallbladder cancer (GBC) subgroup is not an independent superiority claim.

What did the researchers want to learn?

In cancers of the part of the bile duct outside the liver that have been operated on, does gemcitabine after surgery prolong survival or the time before the cancer comes back?

What did this study change?

It did not support routine use of gemcitabine alone after surgery.

Benefit for patients

Relevant to patients with resected biliary cancer.

What did the research find?

No significant superiority could be shown in survival or in the time before the cancer came back; that is, the main goal of the study was not met.

Who does this apply to?

The study focuses on extrahepatic bile duct cancers; it should not be equated with all bile duct cancers.

What did the researchers want to learn?

After biliary tract cancer surgery, does GEMOX chemotherapy prolong the time before the cancer comes back or survival?

What did this study change?

It did not support GEMOX being used as standard treatment after surgery.

Benefit for patients

Relevant to patients with resected biliary cancer.

What did the research find?

No statistically significant superiority could be shown in the time before the cancer came back or in survival; that is, the main goal of the study was not met.

Who does this apply to?

It is not a regimen-for-regimen comparison with the BILCAP or ASCOT studies; the results therefore cannot be compared directly with those studies.

What did the researchers want to learn?

In operated bile duct and gallbladder cancers, does S-1 after surgery prolong survival compared with observation alone?

What did this study change?

It showed a survival benefit for S-1 after surgery; these data come from Japanese patients.

Benefit for patients

Relevant to patients with resected biliary cancer.

What did the research find?

In the first analysis, the three-year survival rate was 77.1% and 67.6% (hazard ratio 0.69). In the current 2026 five-year analysis, the rates were 64% and 52% (hazard ratio 0.72).

Who does this apply to?

The Japanese patient group, access to S-1 and regional practice must be taken into account. It is not a regimen-for-regimen comparison with the BILCAP study.

What did the researchers want to learn?

In advanced biliary tract cancer, does giving gemcitabine together with cisplatin prolong survival compared with gemcitabine alone?

What did this study change?

In advanced biliary cancers, the gemcitabine–cisplatin combination became the basic chemotherapy standard; later immunotherapy studies were built on this foundation.

Benefit for patients

Relevant to the first-line GemCis decision in advanced/metastatic biliary cancer.

What did the research find?

Median overall survival (OS) was 11.7 vs 8.1 months (hazard ratio [HR] 0.64). It cannot be applied directly to adjuvant (postoperative) treatment.

Who does this apply to?

For advanced / unresectable biliary cancer. It should not be confused with postoperative adjuvant decisions.

What did the researchers want to learn?

In advanced biliary tract cancer, does adding durvalumab to chemotherapy prolong survival?

What did this study change?

Immunotherapy plus chemotherapy became one of the first-line options for suitable patients.

Benefit for patients

Relevant to the decision to add durvalumab to GemCis in advanced biliary cancer.

What did the research find?

Adding durvalumab to GemCis (gemcitabine plus cisplatin) improved overall survival (OS) (interim analysis and updated OS are separate). Immunotherapy is not mandatory for all early-stage / resected patients.

Who does this apply to?

No head-to-head superiority claim can be made versus KEYNOTE-966 (different agent / protocol).

What did the researchers want to learn?

In previously untreated advanced biliary tract cancer, does adding pembrolizumab to gemcitabine-cisplatin chemotherapy prolong survival?

What did this study change?

It broadened first-line immunotherapy options in advanced biliary tract cancer.

Benefit for patients

Relevant to the pembrolizumab + chemotherapy option in advanced biliary cancer.

What did the research find?

Median overall survival (OS) 12.7 vs 10.9 months (hazard ratio [HR] 0.83). It has not been proven that pembrolizumab is superior to durvalumab (not a head-to-head study).

Who does this apply to?

A different agent / protocol from TOPAZ-1; there is no direct comparison. The gallbladder cancer (GBC) subgroup is not an independent superiority claim.

What did the researchers want to learn?

In biliary tract cancer that has progressed after first chemotherapy (gemcitabine-cisplatin), does second-line FOLFOX prolong survival compared with supportive care alone?

What did this study change?

It provided randomized survival evidence for FOLFOX in the second line.

Benefit for patients

Relevant to the second-line FOLFOX decision in advanced biliary cancer.

What did the research find?

Median overall survival (OS) 6.2 vs 5.3 months (hazard ratio [HR] 0.69). It has not been shown that every patient should receive second-line FOLFOX.

Who does this apply to?

General condition, previous treatments and molecular features are important.

What did the researchers want to learn?

In advanced biliary tract cancer with an IDH1 gene alteration, does ivosidenib prolong the time before the disease progresses?

What did this study change?

It showed that the IDH1 mutation can be used in treatment selection.

Benefit for patients

Relevant to patients with IDH1-mutant advanced cholangiocarcinoma.

What did the research find?

Median progression-free survival (time before the disease progressed) was 2.7 months and 1.4 months (hazard ratio 0.37). Because patients crossed over from the control group to treatment, it is difficult to interpret overall survival.

Who does this apply to?

Crossover makes the interpretation of survival difficult. IDH1 alterations are not seen with the same frequency in all biliary tract cancers; it applies only to patients who test positive.

What did the researchers want to learn?

In previously treated advanced biliary tract cancer with an FGFR2 gene fusion or rearrangement, does pemigatinib shrink the tumor?

What did this study change?

It showed the clinical importance of FGFR2 molecular testing.

Benefit for patients

Relevant to patients with FGFR2-altered advanced cholangiocarcinoma.

What did the research find?

In the subgroup with an FGFR2 alteration, the tumor shrinkage (response) rate was found to be about 35.5%. There is no comparison group.

Who does this apply to?

It is a single-arm study without a comparison group; a survival advantage over standard chemotherapy has not been shown. Valid only for patients with an FGFR2 alteration.

What did the researchers want to learn?

In advanced biliary tract cancer with an FGFR2 gene fusion or rearrangement, does futibatinib shrink the tumor?

What did this study change?

It broadened FGFR2-targeted treatment options.

Benefit for patients

Relevant to patients with FGFR2 fusion-positive cholangiocarcinoma.

What did the research find?

The tumor shrinkage (response) rate was 42%, and the median duration of response was about 9.7 months.

Who does this apply to?

It is a single-arm study without a comparison group and covers a selected molecular patient group; a survival advantage has not been shown.

What did the researchers want to learn?

In advanced biliary tract cancer with an FGFR2 alteration, previously treated with at least one therapy and not treated with an FGFR inhibitor, does lirafugratinib produce confirmed tumor shrinkage?

What did this study change?

In selected patients not treated with an FGFR inhibitor, it provided single-arm efficacy evidence for a new-generation FGFR2-targeted option.

Benefit for patients

Relevant to patients with FGFR-altered biliary cancer.

What did the research find?

On independent review, in the main efficacy group (114 patients), a tumor shrinkage rate of 46.5%, a median duration of response of 11.8 months, a median progression-free survival of 11.3 months and a median survival of 22.8 months were reported. Because there is no comparison group, this does not mean a survival advantage.

Who does this apply to?

It is a single-arm study; there is no randomized survival comparison against standard treatment. Molecular eligibility is required; access and licensing may vary by country.

What did the researchers want to learn?

In previously treated HER2-positive advanced biliary tract cancer, does zanidatamab shrink the tumor?

What did this study change?

It showed the importance of HER2-targeted therapy in biliary tract cancer.

Benefit for patients

Relevant to patients with HER2-positive advanced biliary cancer.

What did the research find?

In the main efficacy group with HER2 immunohistochemistry (IHC) 2+/3+ and gene amplification, a confirmed tumor shrinkage rate of 41.3% was found.

Who does this apply to?

HER2 protein and gene status are important. Because it is a single-arm study, it does not mean a randomized survival advantage.

What did the researchers want to learn?

In HER2-positive advanced biliary tract cancer, do tucatinib and trastuzumab together shrink the tumor?

What did this study change?

It supported the investigation of HER2-targeted combinations in this disease.

Benefit for patients

Relevant to patients with HER2-positive biliary cancer.

What did the research find?

In the biliary tract group evaluated, a tumor shrinkage rate of about 46.7% was found.

Who does this apply to?

There is no randomized comparison; access to the drug and licensing vary by country. Valid only for selected HER2-positive patients.

What did the researchers want to learn?

Does gemcitabine-cisplatin chemotherapy after surgery prolong the time before the cancer comes back compared with capecitabine?

What did this study change?

It did not make gemcitabine-cisplatin the standard treatment after surgery; it could not show a proven superiority over capecitabine.

Benefit for patients

Relevant to patients with resected biliary cancer.

What did the research find?

In the 2026 final analysis, the median time before the cancer came back was 25.7 months with gemcitabine-cisplatin and 17.9 months with capecitabine; however, the statistical difference was not significant (p=0.097), that is, the main goal of the study was not met. Survival did not improve significantly, and gemcitabine-cisplatin had more side effects.

Who does this apply to?

Additional analyses were performed because the proportional hazards assumption was violated; these do not replace the main analysis. Subgroup signals are exploratory.