article307

MPACT

"Nab-Paclitaxel plus Gemcitabine for Metastatic Pancreatic Cancer". The New England Journal of Medicine. 2013.

Clinical Question

In patients with metastatic pancreatic cancer, does the addition of nab-paclitaxel to gemcitabine improve survival compared with gemcitabine monotherapy?

Bottom Line

In patients with metastatic pancreatic adenocarcinoma, the addition of nab-paclitaxel to gemcitabine resulted in significantly enhanced overall survival, progression-free survival, and response rate, albeit with elevated rates of peripheral neuropathy and myelosuppression.

Major Points

A phase 3 study showed that the combination of nab-paclitaxel and gemcitabine led to a notable survival advantage for patients with metastatic pancreatic cancer over treatment with gemcitabine alone. Key findings included improved median overall survival by 1.8 months and a doubling in the 2-year survival rate with the combination therapy.

Guidelines

As of 2013, there are no specific guidelines that reference the results of this trial.

Design

- Multicenter, open-label, randomized, phase 3 trial.
- N=861 patients with metastatic pancreatic cancer.
- Nab-paclitaxel plus gemcitabine (n=431) versus gemcitabine (n=430).
- Setting: 151 community and academic centers in 11 countries.
- Enrollment: May 2009 to April 2012.
- Analysis: Intention-to-treat.
- Primary outcome: Overall survival.

Population

- Adults (≥18 years) with metastatic adenocarcinoma of the pancreas.
- Karnofsky performance-status score of 70 or more required.
- Patients had not previously received chemotherapy for metastatic disease.

Interventions

- Nab-paclitaxel (125 mg per square meter) followed by gemcitabine (1000 mg per square meter) on days 1, 8, and 15 every 4 weeks.
- Gemcitabine monotherapy (1000 mg per square meter) weekly for 7 of 8 weeks (cycle 1) and on days 1, 8, and 15 every 4 weeks (cycle 2 and subsequent cycles).

Outcomes

- Median overall survival: Nab-paclitaxel–gemcitabine group 8.5 months, gemcitabine group 6.7 months (HR 0.72, 95% CI, 0.62 to 0.83; P<0.001).
- Median progression-free survival: 5.5 months in the nab-paclitaxel–gemcitabine group versus 3.7 months in the gemcitabine group (HR 0.69, 95% CI, 0.58 to 0.82; P<0.001).
- Overall response rate (independent review): 23% in the nab-paclitaxel–gemcitabine group versus 7% in the gemcitabine group (P<0.001).

Criticisms

- Quality of life was not measured.
- The study's open-label design might have influenced assessments.

Funding

Supported by Celgene.