Genentech Inc. and partner OSI Pharmaceuticals Inc. are set to pursue a broader label for Tarceva (erlotinib) in the United States as a first-line treatment of advanced non–small cell lung cancer with epidermal growth factor receptor mutations, after reporting positive top-line results in that setting from a phase III European study.
On Jan. 28, Genentech announced that compared with platinum-based chemotherapy, the EGFR inhibitor Tarceva was shown to improve progression-free survival in an interim analysis of the EURTAC study of 178 newly-diagnosed advanced NSCLC patients who had tested positive for the mutations. Furthermore, safety was in line with Tarceva’s profile. In light of the efficacy and safety results, the trial was halted early on the recommendation of its independent data monitoring committee.
Tarceva is currently approved in the United States and Europe as a maintenance and second-line treatment for advanced or metastatic NSCLC with and without EGFR activating mutations. An estimated 10% of NSCLC carries the EGFR mutations and according to Genentech a first-line indication would mean Tarceva could emerge as the first-choice for that sliver of the patient population, ahead of chemotherapy and other drugs approved for first-line NSCLC.
Genentech’s parent company, Roche, had already submitted a bid to expand the drug’s label to the European Medicines Agency in June 2010.
Then, in November 2010, Roche announced that it was sublicensing a diagnostic assay for EGFR mutations from Genzyme Corporation and collaborating with OSI on the development of a PCR- based companion diagnostic test to identify people with non–small cell lung cancer that harbors EGFR activating mutations.
Genentech and OSI plan to talk to the Food and Drug Administration about possibilities for a first-line indication in NSCLC and also for the companion diagnostic test in development, but timing on these discussions has not yet been decided.
It’s unclear whether the drug would be submitted to the FDA simultaneously with a diagnostic test, which was the case in a recent approval of a new, narrow indication for Herceptin in a particular type of gastric cancer.
The test in development by Roche and OSI was not the same diagnostic used in the EURTAC study, which was designed and sponsored by the Spanish Lung Cancer Group. Genentech said it still needs to validate the test used in the EURTAC study using samples from the trial, prior to talks with FDA. It’s also unclear at this time whether another study beyond EURTAC would be needed to expand the U.S. label.
Genentech did not disclose the magnitude of the benefit for progression-free survival – the primary end point – in the EURTAC trial. Secondary end points include overall survival, 1-year survival, objective response rate, and safety profile.
In the SATURN trial of Tarceva as a maintenance therapy for NSCLC, the drug showed only a modest PFS benefit for NSCLC patients overall (12.3 weeks for the drug versus 11.1 weeks for placebo). Its use as a maintenance treatment has proven controversial since the FDA approved the indication despite a negative vote by an advisory committee.
However, SATURN showed dramatically better results for patients who had EGFR mutations. In this subgroup, which accounted for 11% of the total population, PFS was 44.6 weeks for the treated group versus the 11 weeks for placebo. Based on the data, some physician surveys have suggested more willingness to use Tarceva as a maintenance treatment in the case of EGFR mutations.
Originally published by "The Pink Sheet." Internal Medicine News Digital Network and "The Pink Sheet" are published by Elsevier.