Study Finds Erlotinib Superior to Conventional Chemotherapy in Treatment of EGFR-Mutated Advanced NSCLC

Progression-free survival (PFS) improved significantly in patients with epidermal growth factor receptor (EGFR)—mutated advanced non–small cell lung cancer (NSCLC) treated first line with erlotinib versus platinum-based chemotherapy, according to results of a multicenter European trial presented in June at the ASCO meeting.

Patients treated with EGFR inhibitor had a median PFS of 9.7 months compared with 5.2 months for patients who received chemotherapy. An extensive preplanned subgroup analysis showed a consistent advantage for treatment with erlotinib.

“The study confirms the significant benefit in progression-free survival of erlotinib over standard chemotherapy,” said Rafael Rosell, MD, PhD, head of medical oncology at Catalan Institute of Oncology in Badalona, Spain. “We observed a 63% reduction in the risk of progression or death. The overall survival [OS] data are immature, and there is a high level of known crossover. No new safety findings were seen, as the tolerability of erlotinib was consistent with previous studies.”

The findings came from the final analysis of the phase III European Erlotinib Versus Chemotherapy (EURTAC) randomized trial. Investigators in Spain, France, and Italy participated in the trial, the first ever to compare an EGFR inhibitor and platinum-based chemotherapy in first-line treatment of advanced NSCLC

The trial was limited to patients with EGFR-mutated NSCLC, and investigators screened 1227 patients to identify 174 participants in the EURTAC trial. Only patients who tested positive for EGFR mutations by DNA sequencing and by specific tests for exon 19 and 21 mutations were eligible for the trial.

The patients were randomized to erlotinib 150 mg/day or to a platinum-based chemotherapy doublet. Treatment with erlotinib continued until disease progression, whereas patients in the chemotherapy arm received a maximum of 4 cycles, administered on a 3-week schedule.

The primary endpoint was PFS. An interim analysis in August 2010 showed a significant advantage in favor of the erlotinib arm. At that time, the median PFS was 9.4 months with erlotinib and 5.2 months with chemotherapy, which translated into a statistically significant 58% reduction in the hazard for progression (P <.0001).

The data also showed a 4-month difference in median OS in favor of erlotinib (22.9 vs 18.8 mo), but the difference did not achieve statistical significance (P = .42).

An updated analysis in January 2011 showed an even greater difference in PFS in favor of erlotinib. The 4.5-month difference in the median translated into a 63% reduction in the hazard, which remained statistically significant (P <.0001).

Analysis of best overall response showed 2 complete responses and 48 partial responses for an overall response rate of 58%. That compared with 13 partial responses and an overall response rate of 15% in the chemotherapy arm (P <.0001). Additionally, 18 patients had stable disease during treatment with erlotinib compared with 44 in the chemotherapy arm, resulting in a disease control rate (response plus stable disease) of 79% in the erlotinib group and 66% in the chemotherapy group.

The incidence of grade 3/4 adverse events was substantially lower in the erlotinib arm (45%) compared with the chemotherapy arm (81%). Rosell reported that serious treatment-related adverse events occurred in 16% of chemotherapy patients and 7% of erlotinib patients.

Twice as many patients in the chemotherapy arm required dose modifications or interruptions (53% vs 27%), and almost 3 times as many patients withdrew from the study because of treatment-related adverse events (14% vs 5%).

Rosell R, Gervais R, Vergnenegre A, et al. Erlotinib versus chemotherapy in advanced non-small cell lung cancer patients with epidermal growth factor receptor mutations: interim results of the European Erlotinib Versus Chemotherapy (EURTAC) phase III randomized trial. J Clin Oncol. 2011;29(suppl; abstr 7503).