Three First-line Therapies for Pancreatic Cancer

Increased Survival in Pancreatic Cancer With nab-Paclitaxel Plus Gemcitabine

Von Hoff DD, Ervin T, Arena FP, et al
N Engl J Med. 2013;369:1691-1703

Study Summary

The authors evaluated the efficacy of a doublet regimen of gemcitabine with nab-paclitaxel in the treatment of advanced pancreatic cancer in the first-line setting. A total of 861 patients in this phase 3 trial were randomly assigned to nab-paclitaxel and gemcitabine or gemcitabine alone. Patients assigned to the doublet received nab-paclitaxel (125 mg/m²) followed by gemcitabine (1000 mg /m²) on days 1, 8, and 15 every 4 weeks; those assigned to monotherapy received gemcitabine weekly for 7 of 8 weeks (cycle 1) and then on days 1, 8, and 15 every 4 weeks (cycle 2 onwards).

The primary endpoint was overall survival. Median survival was 8.5 months in the nab-paclitaxel-gemcitabine group as compared with 6.7 months in the gemcitabine-alone arm (hazard ratio, 0.72; 95% confidence interval, 0.62-0.83; P < .001). One-year survival was 35% in the nab-paclitaxel-gemcitabine group vs 22% in the gemcitabine-alone group; response rate was 23% vs 7%, respectively (P < .001). The doublet regimen was associated with more adverse effects, including neutropenia (38% vs 27%), fatigue (17% vs 7%), and neuropathy (17% vs 1%). Neuropathy resolved in most patients.

Viewpoint

Pancreatic cancer is a lethal disease, and despite its relatively low incidence, this illness contributes significantly to the public health burden of cancer-related mortality. New approaches to treatment are urgently needed. This trial establishes the safety and efficacy of a doublet regimen in this setting and is important, particularly given the failure of dozens of "gem-plus" randomized studies.

However, results of this trial must be interpreted in light of the FOLFIRINOX study, which reported a response rate of 31.6% and median survival of 11.1 months, both substantially higher than the doublet gemcitabine/nab-paclitaxel regimen.^[1] However, the FOLFIRINOX study excluded patients > 75 years of age whereas 10% of the study population in the Von Hoff trial was ≥ 75 years. Thus, there are now competing standards of care for patients with advanced pancreatic cancer: FOLFIRINOX for younger, healthy patients who are accepting of an "aggressive" regimen with significant toxicity; gem/nab-paclitaxel for patients who have good or moderate performance status and some comorbidities; and gemcitabine alone for patients with marginal performance status or significant comorbid conditions who would not be expected to tolerate combination regimens.

Abstract

Cite this: Three First-line Therapies for Pancreatic Cancer - Medscape - Nov 22, 2013.

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