O-0006 Dose Escalation to Rash for Erlotinib Plus Gemcitabine in Patients with Metastatic Pancreatic Cancer: The Phase II RACHEL (BO21128) Study

ABSTRACT Introduction Evidence suggests that skin rash may be a surrogate marker for epidermal growth factor receptor (EGFR) inhibitor efficacy. In the PA.3 study, rash (grade ≥2) was predictive of longer survival with gemcitabine plus erlotinib. The phase II, open-label, multicentre, randomised, RACHEL (BO21128) dose-escalation study evaluated whether metastatic pancreatic cancer patients with grade 0/1 rash after 4 weeks of gemcitabine/erlotinib therapy derived benefit from increasing the erlotinib dose beyond the standard 100mg/day, and whether dose escalation could induce rash or increase rash severity. Methods Eligible patients had histologically/cytologically confirmed metastatic pancreatic cancer, no prior systemic therapy for metastatic disease, and performance status 0–1. After a 4-week run-in period of gemcitabine (1000mg/m2, once-weekly) plus erlotinib (100mg/day), patients meeting all eligibility criteria were randomised to gemcitabine (1000mg/m2, days 1, 8, 15, 4-weekly cycle) plus erlotinib (100mg/day) or to gemcitabine (same dose) plus erlotinib dose-escalation (150mg starting dose, increasing by 50mg every 2 weeks to 250mg/day maximum until development of grade 2 rash or other dose-limiting toxicity). Patients who developed grade ≥2 rash during run-in were not randomised and received standard gemcitabine/erlotinib. Primary endpoint: overall survival (OS) between randomised arms; secondary endpoints: progression-free survival (PFS), incidence of grade ≥2 rash, response rate and safety. Results Of 467 enrolled patients, 36 withdrew during run-in and were excluded from the study; 179 had grade 0/1 rash but were ineligible for randomisation; 106 developed grade ≥2 rash during run-in and received standard gemcitabine/erlotinib without randomisation; 146 were eligible for randomisation (75 to standard erlotinib and 71 to dose-escalation erlotinib). Dose-escalation induced grade ≥2 rash in 29 patients (41.4%) versus 7 patients (9.3%) with standard-dose, a difference of 32.1% (95% CI 18.0–46.2; p Conclusion The erlotinib dose-escalation strategy induced rash in 41% of patients, but was not associated with increased clinical benefit compared with the standard erlotinib dose of 100mg/day. Table 1 .