In a phase II trial reported in JAMA Oncology, Rachna T. Shroff, MD, and colleagues found that the addition of nab-paclitaxel to standard gemcitabine and cisplatin resulted in promising outcomes in patients with unresectable locally advanced or metastatic biliary tract cancers.
Rachna T. Shroff, MD
The study included 60 patients enrolled at The University of Texas MD Anderson Cancer Center, Houston, and the Mayo Clinic, Phoenix, between April 2015 and April 2017. The first 32 patients received gemcitabine at 1,000 mg/m2, cisplatin at 25 mg/m2, and nab-paclitaxel at 125 mg/m2 on days 1 and 8 of 21-day cycles. After excess hematologic adverse events were observed among these patients, the remaining 28 patients received 800 mg/m2, 25 mg/m2, and 100 mg/m2, respectively.
Among the 60 patients, 38 (63%) had intrahepatic cholangiocarcinoma, 9 (15%) had extrahepatic cholangiocarcinoma, 13 (22%) had gallbladder cancer, 47 (78%) had metastatic disease, and 13 (22%) had locally advanced disease. The primary endpoint was investigator-assessed progression-free survival in the intent-to-treat population.
Gemcitabine plus cisplatin has previously been reported to result in median progression-free and overall survival of 8.0 and 11.7 months in this setting. In the current study, the median follow-up was 12.2 months. Median progression-free survival and overall survival were 11.8 and 19.2 months. Objective responses (all partial responses) were observed in 45% of patients, and disease control was observed in 84%.
Among 57 patients completing at least 1 cycle of treatment, grade ≥ 3 adverse events occurred in 58%, including 61% of patients in the higher-dose group and 54% in the reduced-dose group. The most common grade ≥ 3 adverse event was neutropenia, which occurred in 33% of patients, including 32% of the higher-dose group and 35% of the reduced-dose group.
The investigators concluded, “Treatment with nab-paclitaxel plus gemcitabine [and] cisplatin prolonged median progression-free survival and overall survival vs those reported for historical controls treated with gemcitabine [and] cisplatin alone. These findings will be tested in a phase III randomized clinical trial.”