Dr. Rachna Shroff

An expert explains what biliary tract cancers are and the current landscape of treatment as well as future advancements. 

Understanding Biliary Tract Cancer and The Current Standard of Care

In the treatment of newly diagnosed biliary tract cancer, the current standard of care involves chemotherapy in combination with immunotherapy, utilizing agents such as Imfinzi (durvalumab) or Keytruda (pembrolizumab), according to Dr. Rachna Schroff, Chief of the Division of Hematology Oncology and AGI medical oncologist at the University of Arizona Cancer Center, in an interview with CURE.

, by lead study author Shroff, indicates that the addition of nab-paclitaxel to the standard gemcitabine and cisplatin regimen (GAP) did not improve overall survival in patients with advanced biliary tract cancer compared to gemcitabine and cisplatin alone, according to study findings published in the 

She further states that ongoing research focuses on enhancing this frontline regimen by integrating additional immunotherapy agents or novel therapeutic approaches. Importantly, the addition of immunotherapy has demonstrated minimal additional toxicity, supporting the feasibility of further treatment intensification.

Overall survival: the length of time from diagnosis or treatment start that patients remain alive.

Genomic profiling: the analysis of a tumor’s genetic mutations to identify potential targets for treatment.

Given the availability of multiple Food and Drug Administration (FDA)-approved targeted therapies, comprehensive genomic profiling at diagnosis is crucial to identify actionable mutations and inform treatment decisions upon disease progression, according to Shroff. Emerging research continues to identify novel targets and therapeutic agents, expanding potential treatment options beyond currently approved therapies. Additionally, she states that studies are investigating mechanisms of resistance in patients receiving targeted treatments and exploring strategies to overcome or bypass resistance, highlighting a critical area for future therapeutic advancements.

Advanced biliary tract cancers basically comprise a heterogeneous group of cancers that includes intrahepatic cholangiocarcinoma, extra hepatic cholangiocarcinoma and gallbladder cancer. Cholangiocarcinoma is just a fancy name for bile duct cancers. These are cancers that start either inside the liver, intrahepatic, or in the larger bile ducts that sit right at the entrance of the liver or outside of the liver, and those are extrahepatic cholangiocarcinoma, and then gallbladder cancer as well. And advanced simply means that this is not something that is resectable, as we call it, or something that can have a surgery to remove the tumor. So, it can either be locally advanced or metastatic, meaning spread to multiple areas.

Transcript was edited for clarity and conciseness.

“SWOG S1815: A Phase III Randomized Trial of Gemcitabine, Cisplatin, and Nab-Paclitaxel Versus Gemcitabine and Cisplatin in Newly Diagnosed, Advanced Biliary Tract Cancers,” By Dr. Rachna T. Shroff, et al. 

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An expert explains that the GAP regimen did not improve overall survival in advanced biliary tract cancer versus the doublet and increased severe side effects.

GAP Triplet May Be Less Safe Than Doublet Chemo in Biliary Tract Cancer

, which combines gemcitabine, cisplatin and nab-paclitaxel, did not improve overall survival in patients with advanced biliary tract cancer compared to the gemcitabine and cisplatin regimen, according to study findings published in 

 Although GAP showed a slight benefit in progression-free survival for patients with gallbladder cancer, it also caused higher rates of severe side effects, including hematologic and nonhematologic toxicities.

CURE spoke with lead study author, Dr. Rachna Schroff, Chief of the Division of Hematology Oncology and AGI medical oncologist at the University of Arizona Cancer Center, to discuss more about the study's findings, including the lack of improvement in median overall survival with the addition of nab-paclitaxel, and the increased toxicity observed with the triplet chemotherapy regimen.

Hematologic toxicities: blood cell-related side effects.

Neutropenia: low white blood cell count, increased infection risk.

Thrombocytopenia: low platelet count, increased bleeding risk.

Overall survival: time from treatment start to death.

Progression-free survival: time without cancer worsening.

Schroff noted that the majority of side effects in the trial were hematologic, so growth factor use for low white blood cells was a routine part of treatment. This approach, which was also permitted by the trial, helped address issues like neutropenia and thrombocytopenia. When given on a 14-day schedule, these side effects were less common.

Shroff also highlighted the availability of novel agents to support platelet levels. While non-hematologic side effects such as neuropathy, fatigue, nausea and vomiting did occur, they were manageable and did not lead to significant dose reductions.

The other big question, of course, when we give a triplet chemotherapy regimen, is toxicity. And not surprisingly, the adding of a third chemotherapy like albumin-bound paclitaxel [nab-paclitaxel], did increase the overall toxicity in the sense that there was a higher number of what we call grade 3 [severe] treatment related adverse events, primarily hematologic toxicities, like low white blood cells, low platelet count, etc., in the GAP arm versus GemCis [gemcitabine-cisplatin]. While there was a higher number of people who had to have dose modifications on the GAP arm, importantly, even with that, their actual rate of people discontinuing treatment from toxicity was relatively similar between the GAP and the GemCis arm. So, the take home points from this large, randomized phase 3 study were that the addition of albumin-bound paclitaxel to gemcitabine and cisplatin did not statistically significantly improve median overall survival. So, GAP did not improve overall survival compared to GemCis, and that there were potentially higher rates of toxicity with a triplet chemotherapy regimen.

But there are subsets of patients that probably could and should be explored to really understand if there could be utility for the triplet chemotherapy regimen, perhaps in gallbladder cancer patients or locally advanced patients.

“SWOG S1815: A Phase III Randomized Trial of Gemcitabine, Cisplatin, and Nab-Paclitaxel Versus Gemcitabine and Cisplatin in Newly Diagnosed, Advanced Biliary Tract Cancers,” By Dr. Rachna T. Shroff, et al. 

Dr. Rachna Shroff

Understanding Biliary Tract Cancer and The Current Standard of Care

GAP Triplet May Be Less Safe Than Doublet Chemo in Biliary Tract Cancer

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