First-line erlotinib therapy was associated with a tripling of progression-free survival rates in patients with advanced non-small cell lung carcinoma (NSCLC) harboring epidermal growth factor receptor (EGFR)-activating mutations, according to results of a Phase III trial reported at the European Society for Medical Oncology Congress.
The median progression-free survival rate was 13.1 months in patients given erlotinib, compared with 4.6 months for patients given the standard chemotherapy doublet of gemcitabine and carboplatin.
“Erlotinib does much better than standard regimens in patients with EGFR-activating mutations. It is preferable to first-line chemotherapy in patients with this disease,” said principal Investigator Caicun Zhou, MD, PhD, Director of Medical Oncology at Shanghai Pulmonary Hospital of Tongji University.
Dr. Zhou noted that patients with good performance status gained the greatest benefit, suggesting that erlotinib should be used as early as possible in these patients.
A once-a-day pill, erlotinib inhibits the tyrosine kinase that is turned on by mutated EGFR protein. In patients with advanced NSCLC, it is currently approved as maintenance or second- or third-line therapy.
For the study, which was funded by Genentech, Dr. Zhou and colleagues screened 549 Asian NSCLC patients who had not received previous chemotherapy for the presence of activating mutations of the EGFR gene. About one-third of the patients harbored the mutations and were enrolled in the trial; 21 patients subsequently dropped out.
The final cohort consisted of 82 patients randomized to receive erlotinib at a dose of 150 mg a day and 72 patients randomized to combination chemotherapy with gemcitabine (1,000 mg/m2 on Days 1 and 8) and carboplatin (area under the curve of 5 on Day 1). Patients continued on the study drugs until they developed unacceptable toxicity or progressive disease.
Patients had an Eastern Cooperative Oncology Group performance status of 0 to 2 and measurable disease. They were stratified by histology, smoking status, and mutation type.
Fewer Side Effects
Results showed that erlotinib was associated with a significant 84% decrease in the risk of disease progression compared with standard therapy, Dr. Zhou said.
Additionally, the disease control rate—defined as the complete response plus the partial response rate plus stable disease—was 96% in the erlotinib arm, compared with 82% in the chemotherapy group, also a significant difference.
Erlotinib was associated with a lower incidence of adverse events, both serious and overall, and there were no unexpected adverse events or interstitial lung disease-like events in either group, he said.
“I prefer to use erlotinib as a first-line treatment among non-small cell lung cancer patients who harbor EGFR activating mutations.”
Study in Whites Under Way
“This is a very important trial,” said ESMO press officer Fortunato Ciardiello, MD, PhD, Professor of Medical Oncology at the Second University of Naples, asked to give some perspective.
“Erlotinib was much better than standard doublet chemotherapy, both in terms of progression-free survival and response rate. The findings strongly argue in favor of using erlotinib or gefitinib, another orally available EGFR tyrosine kinase inhibitor, as first-line therapy in patients with EGFR mutations.”
Dr. Zhou noted that the study was done in an Asian population, 30% of whom harbor the EGFR mutation. In the white population with NSCLC, the figure is about 10%.
A similar study is now under way in white patients, with results expected within the year, Dr. Ciardiello said.
© 2010 Lippincott Williams & Wilkins, Inc.