Correlation of skin rash and overall survival in patients with pancreatic cancer treated with gemcitabine and erlotinib - results from a non-interventional multi-center study

BackgroundGemcitabine/erlotinib treatment offers limited benefit in unselected patients with pancreatic ductal adenocarcinoma (PDAC). Development of skin rash has been associated with favorable outcomes in patients treated with gemcitabine/erlotinib. This study aimed to extend knowledge on the effectiveness of gemcitabine/erlotinib in metastatic PDAC in the context of clinical practice and with focus on skin rash.MethodsThis multicenter, non-interventional study enrolled 376 patients with metastatic PDAC receiving gemcitabine/erlotinib. The primary endpoint was overall survival (OS) in patients with skin rash versus no skin rash. Secondary endpoints included progression-free survival (PFS), treatment satisfaction and safety. All data were analyzed using descriptive statistics. Survival time and time to disease progression were estimated using the Kaplan-Meier method. Effectiveness endpoints were analyzed for subgroups by skin rash grade (no rash, rash grade 1, rash grade >= 2), duration of erlotinib treatment (<= 8weeks, >8weeks), Eastern Cooperative Oncology Group (ECOG) performance status at baseline (0-1, 2) and age (<= 65years, >65years).ResultsWithin the full analysis set (FAS; N=270), 48 patients (17.8%) developed grade 1 rash, 51 patients (18.9%) grade >= 2 rash, while 171 patients (63.3%) did not develop a rash. Median OS of all patients was 9.11months with an OS of 9.93months in rash-positive and 8.68months in rash-negative patients. Median PFS was 5.06months for rash-positive and 4.11months for rash-negative patients. PFS was longer in patients with rash grade >= 2 and in older patients (>65years). Examination using a multivariate Cox proportional model revealed that an age>65years was associated with longer OS (hazard ratio 0.640; p=0.0327) and PFS (hazard ratio 0.642; p=0.0026). Out of the 338 patients in the SAF, 310 patients (91.7%) experienced at least one AE, and 176 patients (52.1%) experienced skin-related side effects, all of which were CTC grade 1 to 3.ConclusionsComparing rash-positive with rash-negative patients showed no significant difference in survival. While patients with rash grade >= 2 and older patients (independent of skin reactions) showed longer PFS, this did not translate into prolonged OS. The study did not reveal new safety signals.Trial registrationClinicalTrials.gov Identifier: NCT01782690, retrospectively registered on 4 February 2013.