The combination of nanoparticle albumin-bound (nab)-paclitaxel and gemcitabine may be comparable in efficacy and safety to other chemotherapy combinations as first-line therapy for advanced or metastatic cholangiocarcinoma, but a phase 2 clinical trial failed to prove that hypothesis.
Among 74 patients with cholangiocarcinoma (CCA) treated with nab-paclitaxel and gemcitabine in a multicenter study, the 6-month progression-free survival (PFS) rate was 61%, which was lower than the 70% or higher rate required to confirm the trial’s primary endpoint, reported Vaibhav Sahai, MBBS, MS, of the University of Michigan in Ann Arbor, and his colleagues.
“Although the trial did not meet its primary efficacy endpoint, the PFS and OS [overall survival] were comparable to those of the gemcitabine plus cisplatin and gemcitabine plus oxaliplatin regimens in the ABC-02 and BINGO trials, respectively. As such, we conclude that combination nab-P and gemcitabine therapy is well tolerated and may be considered as an alternative regimen to current therapeutic approaches in advanced CCA,” they wrote. The report is in JAMA Oncology.
Recent evidence has suggested that nab-paclitaxel may potentiate the activity of gemcitabine by inhibiting cytidine deaminase, a gemcitabine-metabolizing enzyme, thereby allowing active metabolites of gemcitabine to accumulate in tumors, the author noted.
To see whether this observed synergy could translate into clinical benefit, they conducted a trial with 74 patients from 23 community and academic centers in the United States and Europe. The median patient age was 62 (range 36-87) years.
The patients received a median of six treatment cycles and were followed for a median of 10.2 months. Treatment consisted of intravenous nab-paclitaxel at a dose of 125mg/m2, followed by gemcitabine 1,000 mg/m2, on days 1, 8, and 15 of each 28-day treatment cycle until disease progression or unacceptable toxicity.
The investigators explained the statistical design of the trial as follows:
“At completion, the trial required more than 43 of 67 evaluable patients to be alive and progression free at 6 months to conclude that the 6-month PFS rate was at least 70% (vs. a null hypothesis of 55%) based on historical data from the Advanced Biliary Cancer (ABC)–02 and BINGO (Gemcitabine and Oxaliplatin With or Without Cetuximab in Advanced Biliary-Tract Cancer) trials.”
As noted, the 6-month PFS rate in evaluable patients was 61%, which was not sufficient to either prove the alternative hypothesis or reject the null hypothesis.
Median PFS was 7.7 months, median time to progression was 7.7 months, and median overall survival was 12.4 months.
The confirmed best overall response rate was 30%, and the disease control rate was 66%.
In all, 72 of the 74 patients had a treatment-related adverse event, including fatigue in 52 patients, neutropenia in 50, and peripheral neuropathy in 41.
Grade 3 or greater adverse events occurred in 61 patients, with neutropenia in 32 patients as the most common treatment-related hematologic event, and grade 3 or greater fatigue in 10 patients as the most common nonhematologic event of grade 3 or greater.
“On the basis of the adverse event profile, nab-P plus gemcitabine treatment may be considered for patients who are not otherwise considered candidates for cisplatin-based therapy, specifically those with renal dysfunction,” the investigators wrote.
SOURCE: Sahai V et al. JAMA Oncol. 2018 Aug 30. doi: 10.1001/jamaoncol.2018.3277.