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Combination therapy extends survival among patients with advanced pancreatic cancer
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The addition of nab-paclitaxel to gemcitabine significantly improved survival in treatment-naïve patients with metastatic pancreatic cancer, according to results of the phase 3 MPACT study presented at the Gastrointestinal Cancers Symposium.
In a previous phase 1/2 study, nan-paclitaxel (Abraxane, Celgene) plus gemcitabine (Gemzar, Eli Lilly) showed promising activity in patients with advanced pancreatic cancer.
In the phase 3 study, researchers randomly assigned 861 patients to nab-paclitaxel plus gemcitabine (n=431) or gemcitabine alone (n=430). Patients in the combination therapy arm received 125 mg/m² of nab-paclitaxel followed by gemcitabine 1,000 mg/m² on days 1, 8 and 15 every 4 weeks.
Daniel D. Von Hoff, MD, FACP, director of the Translational Genomics Research Institute, and colleagues treated patients until disease progression.
The median age of patients was 63 years, and baseline characteristics were balanced between the two arms, researchers said.
OS served as the primary endpoint.
Patients assigned to the combination regimen experienced a median OS of 8.5 months, compared with 6.7 months for patients assigned to gemcitabine alone (HR=0.72; 95% CI, 0.617-0.835), study results showed.
The combination therapy was associated with higher rates of 1-year survival (35% vs. 22%; P=.0002) and 2-year survival (9% vs. 4%; P=.02).
Median PFS was 5.5 months among patients assigned to the combination regimen compared with 3.7 months for those assigned to gemcitabine alone (HR=0.69; 95% CI, 0.581-0.821). The rate of 1-year PFS also was higher among the combination arm (16% vs.9%; P=.03).
The combination therapy also significantly increased median time to treatment failure (5.1 months vs. 3.6 months; HR=0.70; 95% CI, 0.604–0.803) and overall response rate (23% vs. 7%; RR=3.19; 2.178-4.662), according to study results.
Patients assigned to the combination regimen experienced higher rates of neutropenia (38% vs. 27%), fatigue (17% vs. 7%), peripheral neuropathy (17% vs. 1%) and febrile neutropenia (3% vs. 1%).
For more information:
Von Hoff DD. Abstract #LBA148. Presented at: Gastrointestinal Cancers Symposium; Jan. 24-26, 2013; San Francisco.
Disclosure: Von Hoff reports research funding from Celgene.
Perspective
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Tanios Bekaii-Saab, MD
Protein-bound paclitaxel added to gemcitabine was found to improve all efficacy outcomes (OS, PFS and overall response rate) when compared with gemcitabine alone in patients with chemotherapy-naive metastatic adenocarcinoma of the pancreas (MPCA). These results are very encouraging and may represent an added option to patients with MPCA. However, a number of questions remain unanswered, including the rationale for the statistical changes during the ongoing accrual period, and a closer understanding of the toxicity profile and the toxicity-related deaths on study (reported to be 4% in each arm).
In a previous phase 1/2 study, high expression of secreted protein acidic and rich in cysteine (SPARC) was associated with an improved survival with the combination. The potential predictive value of SPARC needs to be further validated to help justify the use of the more expensive protein-bound paclitaxel over perhaps generic paclitaxel. This gains further relevance given the recent studies in breast cancer and adenocarcinoma of the lung that suggest no benefit from the protein-bound agent compared with the generic form of paclitaxel. Regardless of the above concerns, this is now the second study to suggest improved outcomes for patients with MPCA following many years of nihilism.
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