Efficacy of gemcitabine with erlotinib in rash-positive patients selected according to eligibility for FOLFIRINOX.

Abstract

4108 Background: The efficacy and safety of gemcitabine + erlotinib has not yet been defined prospectively in patients (pts) with metastatic pancreatic cancer (mPC) selected according to the inclusion criteria defined by Conroy et al. for FOLFIRINOX (e. g. ECOG 0-1, age < 75, bilirubin < 1.5xULN). Methods: In this German phase II trial, 150 pts with histologically confirmed mPC were recruited between July 2012 and July 2015 in 20 centers. If pts showed skin rash of any grade within 4 weeks after start of treatment with gemcitabine (1000 mg/m2 weekly) and erlotinib (100 mg daily), this regimen was continued; rash-negative pts were switched to FOLFIRINOX. The primary study endpoint was the 1-year survival rate in rash-positive pts (hypothesis: ≥40%). Results: Ninety pts who were under treatment with gemcitabine + erlotinib for 4 weeks developed skin rash of any grade: the 1-year survival rate in those pts positive for skin rash was 40.0% (95%CI 29.8-50.9); median overall survival (OS) counted from day of first treatment was 10.1 months (mo) (95%CI 9.0-12.5), progression-free survival (PFS) 3.9 mo (95%CI 3.5-4.9), objective response rate (ORR) and disease control rate (DCR) were 21% and 64%, respectively. Median treatment duration with gemcitabine+erlotinib was 3.7 mo (Range 0.7-17.5). In rash-negative pts who were switched to FOLFIRINOX after 4 weeks of gemcitabine + erlotinib (n = 28) the 1-year survival rate was 46.4% (95%CI 27.5-66.1), median OS 10.6 mo (95%CI 6.6-13.6), median PFS 5.2 mo (95%CI 2.3-7.9) and the corresponding ORR and DCR rates were 29 and 54%, respectively. The rate of salvage therapy was 53% after gemcitabine+erlotinib, mostly consisting of 5-FU-based schemas (42 % 5-FU/folinic acid + irinotecan or oxaliplatin, 38% FOLFIRINOX) and 43% after FOLFIRINOX (all pts received gemcitabine, 67% in combination with nab-paclitaxel). In the Intention To Treat (ITT) population (n = 145) OS was 9.7 mon (95%CI 7.8-10.9). Conclusions: In rash-positive pts deemed fit for FOLFIRINOX first-line treatment with gemcitabine + erlotinib appears effective achieving a one-year-survival rate of 40%. Early switch to FOLFIRINOX was an effective strategy in rash-negative patients. Clinical trial information: NCT01729481.