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N Engl J Med. 2013 Oct 31;369(18):1691-703. doi: 10.1056/NEJMoa1304369. Epub 2013 Oct 16.

Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine.

Author information

1
From the Translational Genomics Research Institute, Phoenix, and Virginia G. Piper Cancer Center, Scottsdale - both in Arizona (D.D.V.H., R.K.R.); Cancer Specialists, Fort Myers, FL (T.E.); Arena Oncology Associates, Lake Success (F.P.A.), and Roswell Park Cancer Institute, Buffalo (W.W.M.) - both in New York; University of Washington, Seattle (E.G.C.); Sarah Cannon Research Institute-Tennessee Oncology, Nashville (J. Infante); Princess Margaret Hospital, Toronto (M.M.); Atlanta Cancer Care (T.S.) and Georgia Cancer Specialists (M.N.S.) - both in Atlanta; Blokhin Cancer Research Center, Moscow (S.A.T.); Southern Health, East Bentleigh, VIC (M.H.), Prince of Wales Hospital, Sydney (D.G.), and Bionomics, Thebarton, SA (J. Iglesias) - all in Australia; San Raffaele Scientific Institute, Milan (M.R.); Tom Baker Cancer Centre, Calgary, AB, Canada (S.D.); Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore (D.L.); University of Pittsburgh Medical Center, Pittsburgh (N.B.); Vall d'Hebron University Hospital, Universitat Autònoma de Barcelona, Barcelona (J.T.); Centro Integral Oncológico Clara Campal, Madrid (M.H.); University Hospitals Leuven and Katholieke Universiteit Leuven, Leuven, Belgium (E.V.C.); and Celgene, Summit, NJ (X.W., M.F.R.).

Abstract

BACKGROUND:

In a phase 1-2 trial of albumin-bound paclitaxel (nab-paclitaxel) plus gemcitabine, substantial clinical activity was noted in patients with advanced pancreatic cancer. We conducted a phase 3 study of the efficacy and safety of the combination versus gemcitabine monotherapy in patients with metastatic pancreatic cancer.

METHODS:

We randomly assigned patients with a Karnofsky performance-status score of 70 or more (on a scale from 0 to 100, with higher scores indicating better performance status) to nab-paclitaxel (125 mg per square meter of body-surface area) followed by gemcitabine (1000 mg per square meter) on days 1, 8, and 15 every 4 weeks or gemcitabine monotherapy (1000 mg per square meter) weekly for 7 of 8 weeks (cycle 1) and then on days 1, 8, and 15 every 4 weeks (cycle 2 and subsequent cycles). Patients received the study treatment until disease progression. The primary end point was overall survival; secondary end points were progression-free survival and overall response rate.

RESULTS:

A total of 861 patients were randomly assigned to nab-paclitaxel plus gemcitabine (431 patients) or gemcitabine (430). The median overall survival was 8.5 months in the nab-paclitaxel-gemcitabine group as compared with 6.7 months in the gemcitabine group (hazard ratio for death, 0.72; 95% confidence interval [CI], 0.62 to 0.83; P<0.001). The survival rate was 35% in the nab-paclitaxel-gemcitabine group versus 22% in the gemcitabine group at 1 year, and 9% versus 4% at 2 years. The median progression-free survival was 5.5 months in the nab-paclitaxel-gemcitabine group, as compared with 3.7 months in the gemcitabine group (hazard ratio for disease progression or death, 0.69; 95% CI, 0.58 to 0.82; P<0.001); the response rate according to independent review was 23% versus 7% in the two groups (P<0.001). The most common adverse events of grade 3 or higher were neutropenia (38% in the nab-paclitaxel-gemcitabine group vs. 27% in the gemcitabine group), fatigue (17% vs. 7%), and neuropathy (17% vs. 1%). Febrile neutropenia occurred in 3% versus 1% of the patients in the two groups. In the nab-paclitaxel-gemcitabine group, neuropathy of grade 3 or higher improved to grade 1 or lower in a median of 29 days.

CONCLUSIONS:

In patients with metastatic pancreatic adenocarcinoma, nab-paclitaxel plus gemcitabine significantly improved overall survival, progression-free survival, and response rate, but rates of peripheral neuropathy and myelosuppression were increased. (Funded by Celgene; ClinicalTrials.gov number, NCT00844649.).

PMID:
24131140
PMCID:
PMC4631139
DOI:
10.1056/NEJMoa1304369
[Indexed for MEDLINE]
Free PMC Article

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