Predictive role of skin rash in advanced pancreatic cancer patients treated with gemcitabine plus erlotinib: a systematic review and meta-analysis

Minyan Zeng,1,* Qi Feng,1,* Ming Lu,2 Jun Zhou,2 Zuyao Yang,1,3 Jinling Tang1,3 1Division of Epidemiology, JC School of Public Health and Primary Care, The Chinese University of Hong Kong, Hong Kong SAR, China; 2Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of GI Medical Oncology, Peking University Cancer Hospital & Institute, Beijing, China; 3Cochrane Hong Kong, JC School of Public Health and Primary Care, The Chinese University of Hong Kong, Hong Kong SAR, China *These authors contributed equally to this work Purpose: The survival benefit from gemcitabine plus erlotinib was on average marginal for advanced pancreatic cancer (APC) patients. Skin rash developed shortly after starting treatment seemed to be associated with better efficacy and might be used to assist clinical decision-making, but the results across studies were inconsistent. Thus, we conducted a systematic review and meta-analysis. Methods: PubMed, Embase, Cochrane Central Register of Controlled Trials, three Chinese databases, and the abstracts of important conferences were searched for eligible studies. The primary outcome was overall survival (OS), and the secondary outcomes were progression-free survival (PFS) and objective response. The random-effects model was used to pool results across studies if heterogeneity was substantial. Otherwise, the fixed-effect model was used. Results: A total of 16 studies with 1,776 patients were included. Patients who developed skin rash during treatment had longer OS (8.9 vs 4.9 months, HR=0.57, 95% CI 0.50–0.64) and longer PFS (4.5 vs 2.4 months, HR=0.53, 95% CI 0.40–0.68) than those who did not. A dose–response relationship was also observed for both OS (HR=0.64 for grade-1 rash vs no rash and HR=0.46 for ≥grade-2 rash vs no rash) and PFS (HR=0.72 for grade-1 rash vs no rash and HR=0.43 for ≥grade-2 rash vs no rash). Conclusion: Skin rash was associated with better OS and PFS in APC patients treated with gemcitabine plus erlotinib. It might be used as a marker for efficacy to guide clinical decision-making toward a more precise and personalized treatment. Keywords: pancreatic neoplasms, targeted treatment, acne, prognosi