Addition of Abraxane to Standard of Care May Prolong Survival for Advanced Biliary Cancers

Administration of Abraxane (nab-paclitaxel) plus gemcitabine and cisplatin may prolong survival in patients with newly-diagnosed, advanced and/or unresectable bilary tract cancers, compared to the standard-of-care administration of gemcitabine and cisplatin alone, according to phase 2 study findings published in JAMA Oncology.

To determine new treatments that offer improved survival outcomes, lead study author Dr. Rachna T. Shroff, from the Division of Hematology/Oncology in the Department of Medicine at the University of Arizona Cancer Center, and colleagues conducted the open-label, single-arm, phase 2 clinical trial — designed to evaluate the efficacy of the addition of Abraxane to standard of care in patients with biliary tract cancers.

“The goal was to see what the preliminary efficacy was, looking at (the study) in terms of how long people stay on the regimen without progressing, or what we call progression-free survival,” Shroff said in an interview with CURE^®.

The researchers enrolled 60 patients, including only those who had excellent performance status to ensure it was safe to administer three chemotherapies, explained Shroff. The average age was 58.4 years. Thirty-eight (63%) patients had intrahepatic cholangiocarcinoma, nine (15%) had extrahepatic cholangiocarcinoma, 13 (22%) had gallbladder cancer, 47 (78%) had metastatic disease and 13 (22%) had locally advanced disease.

Investigator-assessed progression-free survival — or the time from treatment to disease worsening – in the intent-to-treat population served as the primary endpoint. The researchers also looked at overall survival and overall response rate – or how much the tumors shrank.

After a median follow-up of 12.2 months, progression-free survival was 11.8 months and median overall survival was 19.2 months. In addition, the partial response rate was 45% and the disease control rate was 84%.

“If you look back at historical data, the median survival for advanced biliary cancers is right around seven to 12 months,” said Shroff. “This is somewhat unprecedented overall survival. In addition, the overall response rate, or percent of tumors that shrank, was 45%. If you look at the landmark study of gemcitabine and cisplatin, the response rate was in the 25% range. This (result) was a dramatic improvement in terms of response rate as well.”

Twelve patients (20%) who presented with unresectable biliary tract cancers at the time of their diagnosis experienced such a dramatic response to the treatment that they offered curative surgery as a result, said Shroff. “Out of those patients, two of those 12 patients had what we call a pathologic complete response, meaning there was absolutely no viable cancer left in their surgical specimen after the tumor was taken out,” she added.

Grade 3 or higher side effects occurred in 33 patients (58%). Neutropenia (an abnormally low count of a type of white blood cell) was the most common side effect, occurring in 19 patients (33%). The rate of neuropathy and other non-hematologic toxicity-related side effects was very low, Shroff noted.

Nine patients (16%) withdrew due to side effects. Twenty-six patients (46%) remained on their starting dose throughout the trial.

Patients started on Food and Drug Administration (FDA)-approved doses of the drugs, but the researchers amended the study and reduced the dosages of gemcitabine and Abraxane when the side effects occurred. The overall tolerance of the regimen improved with the lowered dosages and, therefore, those doses will be used in the upcoming phase 3 trial.

These findings will be further analyzed in a nationwide, randomized, controlled phase 3 clinical trial, sponsored by the National Cancer Institute, enrolling 268 patients to evaluate overall survival with the same regimen compared with standard of care.

“In the United States, we have never had a randomized phase 3 study in biliary cancers,” Shroff said. “This is a fantastic opportunity for our patients to be able to have a clinical trial offered to them, hopefully for an improvement in overall survival and response rate, and to be able to participate in what could potentially be a practice-changing study.”