Dr. Rachna Shroff

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.

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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Dr. Rachna Shroff

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

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