The targeted agent erlotinib raised median progression-free survival to 13.1 months from the 4.6 months seen with standard chemotherapy administered against stage IIIB or IV non-small cell lung cancer (NSCLC) tumors with epidermal growth factor receptor (EGFR) mutations.

The first phase 3 trial to examine whether erlotinib has comparable efficacy and safety to chemotherapy in people with NSCLC whose disease harbors EGFR mutations, the OPTIMAL study was conducted at 22 centers in China. The primary end point analysis of progression-free survival involved 82 patients who had been randomly assigned to receive erlotinib and 72 who had received gemcitabine plus carboplatin (chemotherapy group).

Not only was chemotherapy associated with significantly shorter median progression-free survival, it was also linked with more grade 3 or 4 toxic effects than was erlotinib: 30 (42%) of the chemotherapy patients experienced neutropenia and 29 (40%) developed thrombocytopenia; neither event occurred in any erlotinib patient.  The most common grade 3 or 4 toxic effects for erlotinib were increased alanine aminotransferase concentrations in three of the original 83 patients (4%) in that group and skin rash in two patients (2%).

More treatment-related serious adverse events occurred in the chemotherapy group, with 10 of 72 patients (14%) experiencing decreased platelet count, decreased neutrophil count, and/or hepatic dysfunction. In contrast, such events occurred in two of 83 erlotinib patients (2%), both of whom suffered from hepatic dysfunction.

“Compared with standard chemotherapy, erlotinib conferred a significant progression-free survival benefit in patients with advanced EGFR mutation-positive NSCLC and was associated with more favorable tolerability,” concluded the investigators in their report for The Lancet Oncology (2011;12[8]:735-742). “These findings suggest that erlotinib is important for the first-line treatment of patients with advanced EGFR-mutation-positive NSCLC.”