Gemcitabine-based Combination Therapy for Advanced Pancreatic Cancer: Modestly Superior OS but Worse Toxicities

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(ChemotherapyAdvisor) – Gemcitabine-based combination therapies for patients with advanced pancreatic cancer offer modestly but statistically-significantly improved overall survival (OS) rates -- but at the cost of increased toxicities, according to a meta-analysis of data from 34 randomized clinical trials, published in the European Journal of Cancer.

“The combination chemotherapy as compared to gemcitabine alone significantly improves OS in advanced pancreatic cancer,” Pierosandro Tagliaferri, MD, of the Medical Oncology Unit at Magna Graecia University and the Campanella Cancer Center in Catanzaro, Italy, and coauthors. “However, this advantage is marginal whereas the treatment-related toxicity is increased, suggesting the use of gemcitabine-based combination regimens only in selected patient populations.”

Adding targeted VEGF and EGFR-pathway therapeutics to gencitabine “introduced new and important toxicities, but failed to reach significant benefit,” the authors reported. Similarly, the authors cautioned that trial data show gemcitabine plus irinotecan therapy to involve unjustified toxicities, given the lack of an OS benefit, the authors reported.

The trials included in the study represented a total of 10,660 patients.

Overall, hazard ratio (HR) analysis revealed superior OS for gemcitabine plus a second agent, over gemcitabine monotherapy (pooled HR, 0.93[95% CI: 0.89-0.97]; P=0.001).

Combination therapy benefits appeared to be driven largely by oral fluoropyrimidine-based combinations, which also had the worst grade 3-4 hematological and gastrointestinal toxicities.

“(W)e found the major benefit in patients treated with fluoropyrimidine-based combinations (HR, 0.91), but no significant benefit [over gemcitabine alone] in OS for platinum-based combinations,” reported Dr. Tagliaferri and coauthors.

Tumor response rates, however, suggested advantages for platinum and fluoropyrimidine-based combinations, “suggesting that these schedules may be useful in the neoadjuvant setting, where the aim is to achieve the respectability of the disease,” the authors noted.

Patients undergoing gemcitabine-based combination therapies should be closely monitored for hematological and GI toxicities, the authors emphasized.

“New prospective trials, based on translational approaches and innovative validated biomarkers, are eagerly awaited on this topic,” they wrote.


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