The evidence supporting this protocol is provide by a phase III multicentre international randomised trial (MPACT trial) involving 861 patients comparing nab-paclitaxel 125 mg/m2 followed by gemcitabine 1000 mg/m2 on days 1, 8 and 15 every 4 weeks with gemcitabine 1000 mg/m2 weekly for 7 weeks (cycle 1) then days 1, 8, and 15 every 4 weeks (subsequent cycles) in patients with metastatic pancreatic cancer.r
The primary end point was overall survival and secondary end points were progression-free survival and overall response rate.
In the nab-paclitaxel/gemcitabine group, 41% and 47% of the patients had dose reductions in nab-paclitaxel and gemcitabine respectively. In the gemcitabine group, 33% of patients had dose reductions.r
Kim conducted a systematic review of the role of nab-paclitaxel in pancreatic cancer.r At the time of publication of the review, they had found ten studies reporting median OS for first line gemcitabine and nab-paclitaxel ranging from 8.7 to 13.5 months and 1 year survival ranging from 35 to 62%. Most of these studies were single arm trials.
MPACTr and these further studies showed that older patients receiving gemcitabine and nab-paclitaxel where not at an increased risk of toxicity.
In conclusion, multiple studies have shown that first line gemcitabine and nab-paclitaxel improves survival in patients with metastatic pancreatic cancer with an OS similar to or better than that observed in MPACT. The OS benefit holds regardless of age group or performance status.
The systematic review by Kimr shows that multiple studies have confirmed the efficacy of gemcitabine and nab-paclitaxel in the first line setting in metastatic pancreatic adenocarcinoma.
The median overall survival in the intention to treat population was 8.5 months in the nab-paclitaxel/gemcitabine group compared with 6.7 months in the gemcitabine alone group (HR for death, 0.72; 95% CI, 0.62 to 0.83; p<0.001). The 1 year survival rate in the gemcitabine plus nab-paclitaxel group was 35% compared with 22% in the gemcitabine alone group (p<0.001). The 2 year survival rate in the gemcitabine plus nab-paclitaxel group was 9% compared with 4% in the gemcitabine alone group (p=0.02).r An updated analysis of OS presented at ASCO GI 2014 showed that the survival benefit was further extended in the nab-paclitaxel/gemcitabine group, with a 2.1 month median OS improvement compared to gemcitabine alone (8.7 months vs 6.6 months; HR=0.72; p<0.0001).r
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 (HR for disease progression or death, 0.69; 95% CI, 0.58 to 0.82; p<0.001) and the response rate was 23% vs 7% in the two groups (p<0.001).r
Kaplan-Meier curve for Overall Survival (intention-to-treat population)r
© New England Journal of Medicine 2013
The most common adverse events of grade 3 or higher in the nab-paclitaxel/gemcitabine group were neutropenia, fatigue, and peripheral neuropathy. Febrile neutropenia occurred in 3% vs 1 % of patients in the nab-paclitaxel/gemcitabine and the gemcitabine groups respectively with 26% vs 15% of patients receiving growth factor support in the two groups.r
Patients over the age of 65 years may be at increased risk of adverse events including diarrhoea, decreased appetite, dehydration and epistaxis.r
(grade > 3)
|nab-Paclitaxel plus Gemcitabine