Abraxane combo extends survival in advanced pancreatic cancer


Pancreatic cancer is an aggressive, hard-to-treat disease, especially once it spreads outside the pancreas. Unfortunately, about 80 percent of pancreatic tumors are diagnosed at stage 4. Because of the nature of the disease, even small gains are cause to take notice. At the 2013 Gastrointestinal Cancers Symposium, results of the MPACT study, a phase 3 international trial that examined Abraxane and gemcitabine extended overall survival by more than 7 weeks when compared with gemcitabine alone. Abraxane, called nab-paclitaxel, is a form of Taxol which is encased in a protein and is given intravenously. This formulation helps reduce side effects, such as severe allergic reaction, and the protein albumin may make it easier for the active compound paclitaxel to reach cancer cells than the camphor oil used in traditional Taxol. Daniel Von Hoff, lead investigator of the MPACT study, presented the results at the conference as a late-breaking abstract. The study included 842 patients with newly diagnosed metastatic pancreatic cancer. Researchers found that the combination increased the median overall survival by almost two months (8.5 months compared with 6.7 months), meaning that half of the patients in the Abraxane arm were alive at 8.5 months. Von Hoff noted that the benefit of the Abraxane combination over gemcitabine alone increased over time. At the one-year mark, 35 percent of patients taking Abraxane were alive compared with 22 percent in the gemcitabine-alone arm. Although only a small percentage of patients were followed to the two-year mark, the survival benefit had then doubled (9 percent versus 4 percent). The effect also stretched across various subgroups, even those with poor prognostic factors, such as extent of metastases. The poorer the prognostic factors, the more favorable the addition of Abraxane, Von Hoff said.Patients who went on to second-line therapy after progressing in the MPACT trial also did better if they had been treated in the Abraxane arm. Although side effects were seen with the combination, including fatigue and peripheral neuropathy, more patients in the Abraxane arm were able to complete their treatment, hinting that it was more tolerable than gemcitabine alone. Von Hoff predicted that the combination could become a backbone in new regimens for advanced pancreatic cancer. Philip A. Philip, an oncologist with Karmanos Cancer Institute in Detroit, led the discussion of the study and also proposed Abraxane should be considered with other combinations, as well as in earlier stages of the disease. "The rational in developing nab-paclitaxel in pancreatic cancer was based on hypothesis largely related to targeting the stroma," Philip said. Recent studies have shown that one reason pancreatic cancer may be resistant to standard treatment is the stroma, a matrix of cells and molecules that are tightly knit together around the cancer. If Abraxane can weaken the stroma, gemcitabine may have a better chance in getting to the tumor cells, which could explain the synergistic effect researchers are seeing. "I strongly encourage the investigators to grab this opportunity and go back to the lab to determine the molecular basis of this clinical benefit and its association with any biomarkers, such as SPARC." Research has shown that pancreatic cancers overexpress a protein called SPARC, which may attract Abraxane molecules and subsequently may increase tumor response to the drug. Philips called it an "invaluable opportunity" in developing future trials for this disease. Celgene, the company that produces Abraxane, is planning to submit the drug to the FDA for approval for this patient population by mid-year. Abraxane is already approved for advanced lung and breast cancers.

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