The addition of nab-paclitaxel to gemcitabine-cisplatin appeared to confer clinical benefit in patients with advanced biliary tract cancers compared with historical controls treated with gemcitabine-cisplatin alone, according to the results of a single-arm, open-label, phase 2 clinical trial (ClinicalTrials.gov identifier: NCT02392637). The trial results were recently published in JAMA Oncology.1

The trial included 60 adult patients with various biliary tract cancers: 63% had intrahepatic cholangiocarcinoma, 15% had extrahepatic cholangiocarcinoma, and 22% had gallbladder cancer. Eligible patients had metastatic (78%) or locally advanced disease (22%) and no prior receipt of chemotherapy, unless adjuvant chemotherapy was received more than 6 months before receiving the trial treatment.

The first 32 patients received gemcitabine 1000 mg/m2, cisplatin 25 mg/m2, and nab-paclitaxel 125 mg/m2 on day 1 and day 8 of 21-day cycles. Due to hematologic toxicity, dosing of gemcitabine was reduced to 800 mg/m2 and nab-paclitaxel to 100 mg/m2 for the subsequent 28 patients; cisplatin remained at 25 mg/m2.

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At a median follow-up of 12.2 months, the median progression-free survival (PFS) was 11.8 months (95% CI, 6.0-15.6) and median overall survival (OS) was 19.2 months (95% CI, 13.2 months-not estimable). No patients had a complete response; 45% achieved a partial response and the disease control rate was 84%.

The study authors wrote that these outcomes “appear favorable” compared with those of historical populations with advanced biliary tract cancers treated with gemcitabine-cisplatin in the first-line setting. The median PFS for the historical populations was 8.0 months and median OS was 11.7 months.

More than half of patients (58%) had grade 3 or higher adverse events, with the most common being neutropenia (33%). In all, 9 patients (16%) stopped treatment as a result of toxicity.

“A larger, randomized phase 3 clinical trial is needed to confirm the promising results of the authors’ work,” wrote the authors of a corresponding editorial.2

A phase 3 trial is currently under way (ClinicalTrials.gov identifier: NCT03768414).

Disclosure: The original JAMA Oncology study was funded by Celgene. Some of the authors disclosed relationships with the pharmaceutical industry. For a full list of disclosures, please refer to the original source.

References

  1. Shroff RT, Javle MM, Xiao L, et al. Gemcitabine, cisplatin, and nab-paclitaxel for the treatment of advanced biliary tract cancers: A phase 2 clinical trial [published online April 18, 2019]. JAMA Oncol. doi: 10.1001/jamaoncol.2019.0270
  2. Roth MT, Goff LW. Gemcitabine, cisplatin, and nab-paclitaxel for patients with advanced biliary tract cancer: closing the GAP [published online April 18, 2019]. JAMA Oncol. doi: 10.1001/jamaoncol.2019.0269