Gastroenterology Xagena

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Metastatic adenocarcinoma of the pancreas: weekly Nab-paclitaxel plus Gemcitabine improves survival versus Gemcitabine alone

A phase III clinical trial of the drug Abraxane ( nanoparticle albumin-bound Paclitaxel; Nab-Paclitaxel ) in combination with current standard of care Gemcitabine ( Gemzar ) in patients with advanced pancreatic cancer has demonstrated substantially improved survival times, with double the number of patients surviving two years.

The MPACT ( Metastatic Pancreatic Adenocarcinoma Clinical Trial ) investigation involved 861 treatment naïve patients internationally.
Patients were randomised to receive either Nab-paclitaxel plus Gemcitabine ( 125 mg/m2 followed by 1000 mg/m2 Gemcitabine for 3 weeks followed by a week of rest ) or Gemcitabine alone ( 1000 mg/m2 administered weekly for 7 weeks followed by a week of rest followed by cycles of weekly administration for 3 weeks followed by one week of rest ).
The primary endpoint for the study was improvement in overall survival. Secondary endpoints were progression-free survival, and overall response rate determined by independent radiological review. Other endpoints included progression-free survival, overall response rate determined by investigator and the safety and tolerability of this combination in this patient population.

Researchers found those patients treated with Nab-Paclitaxel plus Gemcitabine had a statistically significant improvement in overall survival compared to patients receiving Gemcitabine alone ( median of 8.5 vs 6.7 months ) ( hazard ratio, HR=0.72, P=0.000015 ).
Moreover, Nab-Paclitaxel plus Gemcitabine has demonstrated a 59% increase in one-year survival ( 35% vs 22%, p=0.0002 ) and has demonstrated double the rate of survival at two years ( 9% vs 4%, p=0.02 ) as compared to Gemcitabine alone.

Nab-Paclitaxel plus Gemcitabine has also demonstrated statistically significant improvements in key secondary endpoints compared to Gemcitabine alone, including a 31% reduction in the risk of progression or death with a median progression-free survival of 5.5 vs 3.7 months ( HR=0.69, P=0.000024 ) and an overall response rate ( ORR ) of 23% compared to 7% ( response rate ratio of 3.19, p=1.1 x 10-10 ).
Another endpoint assessed included time to treatment failure, which was significantly improved with the Nab-Paclitaxel combination compared to Gemcitabine alone ( median 5.1 vs 3.6 months ) ( HR=0.70, P less than 0.0001 ).

The most common grade greater than or equal to 3 treatment-related adverse events in the study for Nab-Paclitaxel plus Gemcitabine versus Gemcitabine alone were neutropenia ( 38% vs 27% ), fatigue ( 17% vs 7% ), and neuropathy ( 17% vs 1% ).
In the Nab-Paclitaxel plus Gemcitabine arm, the median time to neuropathy improvement was 29 days. There was no difference in serious life threatening toxicity ( 4% in each arm ).

Advanced pancreatic cancer is a difficult-to-treat cancer with the lowest survival rates among all cancer types. Across all patients with pancreatic cancer, relative 5-year survival is 6% and is less than 2% for those with advanced disease. There are two main types of pancreatic cancer: adenocarcinomas, which accounts for approximately 90% of all pancreatic cancer, and neuroendocrine tumors. Pancreatic cancer is relatively uncommon with new cases accounting for only 2.1% of all newly diagnosed cancers. However, pancreatic cancer is the fourth most common cause of cancer death for men and women in the United States and Australia, and the ninth most commonly diagnosed cancer in Australia. ( Xagena )

Source: American Society of Clinical Oncology ( ASCO ) - Gastrointestinal Cancers Symposium, 2013