A systemic review and meta-analysis to evaluate the efficacy and postprogression survival of second-line chemotherapy for gemcitabine-refractory pancreatic cancer.

Abstract

e15768 Background: We previously reported positive relationship between overall survival (OS) and both of postprogression survival (PPS) and post-trial anti-cancer therapies in first-line pancreatic cancer patients. We conducted a meta-analysis to gain a better understanding of the impact of PPS and post-trial anti-cancer therapies on OS and to determine the efficacy of second-line systemic therapy. Methods: We searched randomized trials of second-line systemic therapy for pancreatic cancer patients. We evaluated the relation between OS and either progression-free survival (PFS) or PPS and calculated the pooled effect size by using random effects models. Results: Eleven randomized trials with 23 treatment arms that involved examining 2267 patients were analyzed. Median OS was strongly associated with median PPS and PFS (r = 0.908 and 0.754, respectively), but no correlation between rate of post-trial anti-cancer therapies and OS was detected (r = 0.050). Average OS, PFS and PPS were significantly longer in recent trials than in older trials, (6.08 versus 4.17 months, p < 0.001), (2.65 versus 1.95 months, p < 0.001) and (3.43 versus 2.25 months, p < 0.001), respectively. Overall, experimental therapies compared to control did not significantly improve PFS (HR, 0.83; 95% CI, 0.67-1.03; I2 = 73%) or OS (HR, 0.89; 95% CI, 0.72-1.11; I2 = 69%). When the analysis was restricted to fluoropyrimidine compared to irinotecan or oxaliplatin in combination with fluoropyrimidine, each therapy produced advantage in a term of PFS (HR, 0.65; 95% CI, 0.47-0.88; I2 = 39% for irinotecan, HR, 0.81; 95% CI, 0.67-0.98; I2 = 13% for oxaliplatin) but only irinotecan produced advantage in a term of OS (HR, 0.70; 95% CI, 0.55-0.89; I2 = 0% for irinotecan, HR, 1.04; 95% CI, 0.65-1.65; I2 = 82% for oxaliplatin). Conclusions: Although second-line treatment benefit for OS can be skewed by PPS in patients with gemcitabine-refractory pancreatic cancer, the effects of subsequent therapies are weak in the salvage setting.