Gemcitabine Plus Erlotinib for Advanced Pancreatic Cancer: A Systematic Review with Meta-Analysis

<div><p>Background</p><p>This study aims to comprehensively summarize the currently available evidences on the efficacy and safety of gemcitabine plus erlotinib for treating advanced pancreatic cancer.</p> <p>Methodology/Principal Findings</p><p>PubMed, EMBASE, The Cochrane Library and abstracts of recent major conferences were systematically searched to identify relevant publications. Studies that were conducted in advanced pancreatic cancer patients treated with gemcitabine plus erlotinib (with or without comparison with gemcitabine alone) and reporting objective response rate, disease control rate, progression-free survival, time-to-progression, overall survival, 1-year survival rate and/or adverse events were included. Data on objective response rate, disease control rate, 1-year survival rate and adverse events rate, respectively, were combined mainly by using Meta-Analyst software with a random-effects model. Data on progression-free survival, time-to-progression and overall survival were summarized descriptively. Sixteen studies containing 1,308 advanced pancreatic cancer patients treated with gemcitabine plus erlotinib were included. The reported median progression-free survival (or time-to-progression), median overall survival, 1-year survival rates, objective response rates and disease control rates were 2–9.6 months, 5–12.5 months, 20%–51%, 0%–28.6% and 25.0%–83.3%, respectively. The weighted 1-year survival rate, objective response rate and disease control rate based on studies reporting robust results were 27.9%, 9.1% and 57.0%, respectively. According to the studies with relevant data, the incidences of total and severe adverse events were 96.3% and 62.9%, respectively. The most frequently reported adverse events were leucopenia, rash, diarrhea, vomitting, neutropenia, thrombocytopenia, anaemia, stomatitis, drug-induced liver injury, fatigue and fever. Compared with gemcitabine alone, the progression-free survival and overall survival with gemcitabine plus erlotinib were significantly longer, but there were also more deaths and interstitial lung disease-like syndrome related to this treatment.</p> <p>Conclusions/Significance</p><p>Gemcitabine plus erlotinib represent a new option for the treatment of advanced pancreatic cancer, with mild but clinically meaningful additive efficacy compared with gemcitabine alone. Its safety profile is generally acceptable, although careful management is needed for some specific adverse events.</p> </div

Basic characteristic of included studies.

<p>N, sample size; AE, adverse event; KFS, Karnofsky performance score; RECIST, Response Evaluation Criteria In Solid Tumors; NCI CTC, National Cancer Institute Common Terminology Criteria; GEM, gemcitabine; ERL, erlotinib; NA, not available; ECOG, Eastern Cooperative Oncology Group; RCT, randomized controlled trial.</p

Forest plot of meta-analysis on disease control rates.

<p>Legends: Group A: retrospective small studies; Group B: prospective small studies; Group C: prospective large studies.</p

Forest plot of meta-analysis on 1-year survival rates.

<p>Forest plot of meta-analysis on 1-year survival rates.</p

Results of subgroup analyses for objective response rate and disease control rate.

<p>Results of subgroup analyses for objective response rate and disease control rate.</p

Flow chart of study selection.

<p>Flow chart of study selection.</p

Selected adverse events of gemcitabine/erlotinib treatment for advanced pancreatic cancer.

<p>N, total number of patients; ILD, interstitial lung disease.</p