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Nab-paclitaxel plus gemcitabine may be new standard for metastatic pancreatic cancer
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CHICAGO — The addition of nanoparticle albumin-bound paclitaxel to gemcitabine increased response and extended OS compared with gemcitabine alone in patients with metastatic pancreatic cancer, according to results of an international randomized, phase 3 study presented at the ASCO Annual Meeting.
“Nab-paclitaxel plus gemcitabine was superior to gemcitabine [alone] across all efficacy endpoints [and] had an acceptable toxicity profile,” Daniel D. Von Hoff, MD, FACP, physician in chief and director of translational research at the Translational Genomics Research Institute in Phoenix, and colleagues wrote. “[It] is a new standard for the treatment of metastatic pancreatic cancer that could become the backbone for new regimens.”
In preclinical models of pancreatic cancer, nab-paclitaxel (Abraxane, Celgene) showed activity as a single agent and in combination with gemcitabine (Gemzar, Eli Lilly). The combination also showed promise in a previous phase 1/2 study that included patients with metastatic pancreatic cancer, according to background information provided by researchers.
The current investigation included 861 patients (median age, 63 years; range, 27-88) with metastatic disease and a Karnofsky performance status ≥70. Eighty-four percent of patients had advanced disease with liver metastases, and 46% had at least three metastatic sites. The patients were undergoing treatment at 151 academic and community centers.
Researchers randomly assigned half of the patients to nab-paclitaxel 125 mg/m2 plus gemcitabine 1,000 mg/m2 on days 1, 8 and 15 every 4 weeks. The other half received gemcitabine alone 1,000 mg/m2 weekly for 7 weeks, followed by 1 week of rest. They then received gemcitabine alone 1,000 mg/m2 on days 1, 8 and 15 every 4 weeks thereafter.
The median duration of treatment was 3.9 months among patients assigned to the combination arm and 2.8 months among those who received gemcitabine alone.
OS served as the primary endpoint. Secondary endpoints were PFS and overall response rate as confirmed by independent review.
The combination regimen was associated with longer median OS (8.5 months vs. 6.7 months; HR=0.72; 95% CI, 0.617-0.835) and median PFS (5.5 months vs. 3.7 months; HR=0.69; 95% CI, 0.581-0.821). The overall response rate was 23% among patients assigned to nab-paclitaxel plus gemcitabine compared with 7% among patients assigned to gemcitabine alone. Metabolic response determined by PET in 257 patients also was higher among those assigned to the combination treatment (63% vs. 38%; P=.000051).
Researchers reported higher rates of grade 3 or grade 4 neutropenia (38% vs. 27%), fatigue (17% vs. 7%), diarrhea (6% vs. 1%) and febrile neutropenia (3% vs. 1%) in the combination arm.
The rate of grade 3 or grade 4 peripheral neuropathy also was higher among those treated with nab-paclitaxel plus gemcitabine (17% vs. 1%). Peripheral neuropathy improved to grade 1 or less in a median 29 days, and 44% of patients resumed treatment with nab-paclitaxel, according to researchers.
For more information:
Von Hoff DD. Abstract #4005. Presented at: ASCO Annual Meeting; May 31-June 4, 2013; Chicago.
Perspective
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Tanios Bekaii-Saab, MD
These results are very encouraging and now represent an added option to patients with metastatic adenocarcinoma of the pancreas (MPCA). In a previous phase 1/2 study, high expression of SPARC (secreted protein acidic and rich in cysteine) 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. It is a welcome addition, especially that the other option — FOLFIRINOX — remains highly toxic and limited to a subgroup of high-performing patients.
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