The combination of two chemotherapy agents-nab-paclitaxel and gemcitabine-improves survival for patients with metastatic pancreatic cancer, according to the results of a phase III trial.
The combination of two chemotherapy agents-nab-paclitaxel and gemcitabine-improves survival for patients with metastatic pancreatic cancer. The results of the phase III trial are published in the New England Journal of Medicine. Initial results were presented at the 2013 Gastrointestinal Cancers Symposium held in San Francisco in January.
The 861-patient, international trial showed that chemotherapy-naive patients treated with the combination regimen lived 1.8 months (on average) longer compared with patients treated with gemcitabine alone.
This combination was approved by the US Food and Drug Administration (FDA) in September for the treatment of late-stage pancreatic cancer as part of the FDA’s priority review program.
Daniel Von Hoff, MD, FACP, of the Translational Genomics Research Institute in Phoenix, and colleagues showed that the median overall survival in patients receiving the combination was 8.5 months compared with 6.7 months for those receiving monotherapy chemotherapy (P < .001).
At 1 year, the survival rate was 35% in the combination treatment arm and 22% in the control arm, and 9% and 4% at 2 years, respectively.
Progression-free survival (PFS) and response rates were also improved. In the combination arm, the median PFS was 5.5 months compared with 3.7 months in the gemcitabine arm (P < .001). Response rates were 23% and 7% in the combination and control arms, respectively (P < .001). The median time to treatment failure was 5.1 months in the combination arm and 3.6 months in the gemcitabine arm (P < .001).
The proportion of patients with serious adverse events was equal in both treatment groups.
The combination increased the rates of peripheral neuropathy and myelosuppression. Neutropenia increased from 27% in the gemcitabine arm to 38% in the combination arm. Fatigue and neuropathy also increased. The toxicities of the combination therapy are manageable, according to the authors. “Fevers, incidence of infections, and pneumonitis are other side effects to watch out for,” said one of the study authors, Ramesh K. Ramanathan, MD, of the Translational Genomics Research Institute and medical director of the Virginia G. Piper Cancer Center Clinical Trials Program at Scottsdale Healthcare in Phoenix.
Pancreatic cancer is currently the fourth leading cause of death from cancer in the United States, with no targeted agents and few combination therapies that have been shown to improve survival for this mostly aggressive cancer. Gemcitabine, approved in 1997, remains the mainstay first-line treatment for patients with metastatic disease. According to the authors, the 1-year survival rate of advanced pancreatic cancer patients on a gemcitabine regimen is only 17% to 23%.
Patients were randomized one-to-one to receive weekly IV infusions of nab-paclitaxel at a dose of 125 mg2 followed by a weekly gemcitabine dose of 1,000 mg2 for 3 weeks, 1 week off, and then two more weekly doses of gemcitabine for 7 out of 8 weeks.
The median age of patients in the trial was 63 years. Ten percent of patients were over 75 years old. Fifty-eight percent of patients were male. The majority (84%) of patients had liver metastases, and 39% had lung metastases.
“Until recently, the standard treatment was one chemotherapy agent, gemcitabine,” said Ramanathan. “There have been almost 30 studies that had not shown a benefit in pancreatic cancer compared to gemcitabine.”
Another chemotherapy combination, FOLFIRINOX, was also shown to improve survival by 4.3 months compared with gemcitabine for these advanced cancer patients in phase II and III studies; however, the studies excluded patients over 75 years of age. Dr. Ramanathan noted that the nab-paclitaxel plus gemcitabine combination appears to be slightly better tolerated than FOLFIRINOX, although the two regimens have not been compared head-to-head in a trial. “The significance of the current study is that this chemotherapy combination showed that survival of patients was improved and the combination was fairly well tolerated,” said Ramanathan.
“We believe that this is a significant advance and a good treatment option for patients with good performance status and minimal symptoms,” Ramanathan added. “We now have two treatment options for pancreatic cancer patients.”