Results of a phase III trial of erlotinib (OSI-774) combined with cisplatin and gemcitabine (GC) chemotherapy in advanced non-small cell lung cancer (NSCLC)

Abstract

7010 Background: Oral erlotinib is a potent HER1/EGFR tyrosine kinase-phosphorylation inhibitor with single-agent antitumor activity and has shown additive effects when added to chemotherapy in preclinical models. TALENT was a placebo-controlled study in patients (pts) with previously untreated advanced NSCLC to receive erlotinib at 150mg/d or placebo (PBO) with 6 cycles of gemcitabine and cisplatin (GC) followed by monotherapy. The primary endpoint was duration of survival with secondary efficacy endpoints of: time to progression, response rate, duration of response (using RECIST); pharmacokinetic and pharmacodynamic parameters; quality of life (using the Lung Cancer Symptom Scale). EGFR and HER2 expression rates were also assessed. A standard safety analysis was done. Methods: Chemotherapy was given for a maximum of 6 cycles after which patients continued on study drug until disease progression (PD). Treatment with study drug beyond PD was permitted. Eligibility criteria for both parts of the study included: chemo-naive patients with unresectable stage III or IV NSCLC; age ≥18 years and ECOG PS of 0–1. Results: A total of 1172 pts were enrolled from 164 sites worldwide. The demographic and disease characteristics were well balanced across the two treatment groups. There were no statistically significant differences in overall survival (OS), time to progression (TTP) as described in the table below and quality of life (time to symptomatic progression [TSP]). The toxicity profile of erlotinib combined with GC was not significantly inferior to GC alone, with the exception of increased incidences of grade 3/4 diarrhea (<1% placebo vs. 6% erlotinib) and grade 3/4 skin rash (<1% placebo vs. 10% erlotinib). Conclusions: Erlotinib in combination with GC did not improve survival or other treatment outcomes in patients with advanced NSCLC. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Roche Lilly AstraZeneca Merck; Eli Lilly; AstraZeneca; Bristol-Myers Squibb