FIRST LINE ERLOTINIB IN EGEFR MUTATED LUNG CANCER

January 28, 2011 — In patients with newly diagnosed nonsmall-cell lung cancer (NSCLC), erlotinib (Tarceva) can significantly extend progression-free survival, according to the interim results of a phase 3 trial.
An independent data-monitoring committee has recommended that the European Randomized Trial of Tarceva vs Chemotherapy be stopped early because it has met its primary end point. The data showed that, compared with a platinum-based chemotherapy regimen, erlotinib significantly extended progression-free survival in patients with NSCLC tumors withepidermal growth-factor receptor (EGFR)-activating mutations.
EURTAC was sponsored by the Spanish Lung Cancer Group, which conducted it in conjunction with researchers in France and Italy. It is the first phase 3 study to show a progression-free survival benefit with first-line treatment in a Western population with advanced NSCLC with EGFR mutations.
Although the full results from EURTAC are not publicly available, the data will be submitted for presentation at a future medical meeting, according to the manufacturer.
Erlotinib is a tyrosine kinase inhibitor, which acts on the EGFR. It is currently indicated as maintenance therapy for patients with locally advanced or metastatic NSCLC who have failed other treatment regimens, and as first-line treatment for patients with locally advanced, unresectable, or metastatic pancreatic cancer.
Previous Results Promising
As previously reported by Medscape Medical News, the OPTIMAL study also found that erlotinib extended progression-free survival when used as first-line therapy in advanced NSCLC. That study was conducted in an Asian population, and progression-free survival tripled in patients with EGFR-activating mutations who were treated with erlotinib.
The results of the OPTIMAL study were presented at the 2010 European Society for Medical Oncology Congress. At that time, lead author Caicun Zhou, MD, from Shanghai Pulmonary Hospital, Tongji University, China, told Medscape Medical News that "the study shows us that erlotinib does much better than standard regimens in patients with EGFR-activating mutations."
"Progression-free survival tripled in patients on erlotinib," he said. "It should therefore be considered in preference to first-line chemotherapy in patients with this distinct disease."
Extending Indication
Erlotinib is being developed and marketed by OSI Pharmaceuticals, in partnership with Genentech in the United States, Chugai in Japan, and Roche in the rest of the world.
The new trial compared erlotinib with a regimen of platinum-based chemotherapy (cisplatin/gemcitabine, cisplatin/docetaxel, carboplatin/gemcitabine, or carboplatin/docetaxel). The primary end point was progression-free survival; secondary end points included overall survival, 1-year survival, objective response rate, and safety profile.
The manufacturer notes that a preliminary safety analysis showed that it was consistent with previous studies of this agent.
"We are pleased that the EURTAC study so quickly revealed [that erlotinib] may be a viable alternative to platinum-based chemotherapy in newly diagnosed NSCLC patients with EGFR-activating mutations," said Naoki Okamura, chief executive officer of OSI Pharmaceuticals, in a statement. "The interim analysis of the EURTAC study reinforces the role that [erlotinib] may have in treating patients beyond the Asian population, which has a historically higher instance of EGFR-activating mutations."
In June 2010, Roche applied to the European Medicines Agency to extend the indication and include first-line treatment for patients with advanced NSCLC whose tumors harbor EGFR-activating mutations. On the basis of the EURTAC data, OSI and Genentech have announced plans to discuss similar extended indications with the US Food and Drug Administration. Roche and OSI will collaborate regarding submissions to other health authorities.