7190 Background: Erlotinib is an orally active and selective inhibitor of HER1/EGFR tyrosine kinase. In the BR.21 phase III trial, erlotinib significantly prolonged survival, delayed symptom progression, and improved quality of life in NSCLC patients (pts) (Shepherd et al, NEJM, 2005;353:123). The EAP is an open label, non-randomized, multicentre phase IV trial.
METHODS: Eligibility criteria included stage III/IV NSCLC pts who failed or were unsuitable for chemotherapy. Pts were given oral erlotinib, 150 mg/d, for as long as treatment provided clinical benefit without unacceptable toxicity. Pts were monitored monthly.
RESULTS: In Dec 05, data were available for 1,140 pts from 25 countries, median age 64 y (range 25-91). Key base-line characteristics (% pts) were: males 58%; Caucasian/Oriental 82/15; non-smoker/former or current-smoker 26/73. The % pts with ECOG PS 0/1/2/3 were 20/52/20/8. Most pts (55%) had adenocarcinoma. The % pts receiving erlotinib as 1st/2nd/3rd-line treatment were 12/47/40. As expected, rash was a common adverse event (AE: any grade [gr]: 65%; gr 3/4: 9%). Full safety data were available for 581 pts. Unexpected erlotinib-related AEs were only seen in <2% pts. Erlotinib-related AEs leading to treatment discontinuation were GI disorders in 21 pts (12 pts had gr 3/4 AEs) and skin disorders in 14 pts (6 pts had gr 3/4 rash). Only 10% of pts had dose reductions, mainly due to rash (66%; gr 3 in 8 pts) and diarrhea (17%; gr 3 in 2 pts). The median daily dose of erlotinib was 150mg. Serious erlotinib-related AEs were GI disorders (19 AEs; 11 gr 3/4), mainly diarrhea (8 AEs, 5 were gr 3). Pt accrual and analyses of response, survival data and assessment of various predictive biomarkers are ongoing. Response and survival data will be presented.
CONCLUSIONS: These interim safety results of erlotinib in the real-life clinical setting in a large number of unselected pts with advanced NSCLC confirm the good tolerability observed in clinical trials. To date, the trial demonstrates that erlotinib is well tolerated, thus, allowing full dose administration to most pts. [Table: see text].
CONCLUSION: As expected, all stratification factors were prognostic, with LDH being the most important factor (HR 2.2). The addition of Obl to DTIC treatment improved outcomes for all efficacy end points. A statistical interaction between Obl treatment and LDH was found for survival. Multivariate analysis was significant in all efficacy end points. Patients with abnormal baseline LDH, already understood to have a poor prognosis, were unlikely to benefit from this therapy and should not be included in future trials of combination oblimersen treatments. [Table: see text] No significant financial relationships to disclose.