The targeted drug erlotinib nearly triples progression-free survival (PFS), and is better tolerated, compared with standard chemotherapy as the initial treatment for patients with advanced non-small-cell lung cancer (NSCLC) whose tumours harbour epidermal growth factor receptor (EGFR) mutations. The results suggest that erlotinib should be one of the first-line treatments now considered for advanced NSCLC in patients with activating EGFR mutations.

Despite progress in recent years, lung cancer remains the leading cause of cancer death worldwide. Increasingly, research has focused on identifying potential biomarkers to prolong survival from new targeted drugs and optimise treatment decisions for individual patients. To date, the most promising of these markers is EGFR mutation status. Previous studies have shown that NSCLC patients with EGFR mutations respond well to tyrosine kinase inhibitor (TKI) therapies such as erlotinib.

The OPTIMAL study is the first phase 3 trial to examine whether erlotinib has comparable efficacy and safety to chemotherapy in patients whose lung cancer harbours EGFR mutations. 165 patients were recruited from 22 centres across China and randomly assigned to erlotinib (83 patients) or a standard platinum chemotherapy regimen of gemcitabine and carboplatin (82).

Erlotinib significantly prolonged median PFS compared with chemotherapy (13.1 months vs 4.6 months).

Serious treatment-related side-effects were only reported in 2% of patients treated with erlotinib compared with 14% given chemotherapy. Grade 3 and 4 toxic effects were also more common in patients receiving chemotherapy, with 42% of patients experiencing neutropenia (low white blood count) and 40% thrombocytopenia (abnormally low number of platelets in the blood) compared with no patients taking erlotinib.

The most frequently reported grade 3 or 4 toxic effects with erlotinib were increased alanine aminotransferase concentrations (4%) and skin rash (2%).

The authors say: "To our knowledge, OPTIMAL is the first phase 3 study to show that patients with EGFR mutation-positive NSCLC who receive erlotinib can live for more than a year without disease progression and also clearly shows the clinical usefulness of testing for a molecular biomarker in lung cancer to guide treatment and improve patient outcomes."

They conclude: "We recommend that EGFR TKIs be regarded as the first-line treatment of choice for this subgroup of patients and chemonaive patients should undergo EGFR mutation testing wherever possible."

In a Comment, Tetsuya Mitsudomi from Aichi Cancer Center Hospital, Nagoya, Japan says: "OPTIMAL clearly shows the importance of EGFR mutation testing and patient selection according to these test results for use of erlotinib...EGFR TKIs are undoubtedly key drugs for patients with EGFR mutations and should be used early in treatment.

However, when EGFR test results cannot be obtained in a reasonably short timeframe, first-line chemotherapy and second-line EGFR TKI after progression is a reasonable option if the patient is later shown to be EGFR mutation-positive."

Source: Lancet Oncology