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Roche Gets Positive CHMP Review for Tarceva as First-line Treatment in EGFR-mutated NSCLC


Originally published July 22. This article has been updated to include information on Roche/Genentech's data submission plans for Tarceva to UK's NICE.

By Turna Ray

Following a positive opinion this week from the European Medicines Agency's Committee for Medicinal Products for Human Use, Roche is hoping that the European Commission will approve its application to expand Tarceva's use as a front-line non-small cell lung cancer treatment in patients with EGFR mutations.

"The CHMP positive opinion for Tarceva is an important step forward in bringing personalized healthcare to patients with EGFR-activating mutation-positive lung cancer in the first-line setting," a Genentech spokesperson told PGx Reporter. "This is not the final decision; it is a recommendation to the EC." Tarceva is marketed by Roche subsidiary Genentech and Astellas.

According to the spokesperson, the EC is expected to issue a decision in September regarding Tarceva as a first-line treatment for EGFR-mutation-positive NSCLC. CHMP's recommendation is a sign that the firm will gain an additional indication for the drug in European markets, since the EC usually follows the recommendation of its advisory body. EC's decision will be enforced in 27 EU member states, as well as Iceland and Norway.

Tarceva is currently marketed in Europe as a treatment for advanced or metastatic NSCLC irrespective of a patient’s EGFR status. The drug is used as maintenance therapy after patients receive initial chemotherapy and when the disease advances despite chemotherapy treatment.

The CHMP opinion comes as Roche is in discussions with regulators in the US to similarly expand the drug's use into the EGFR-mutated NSCLC population. The company expects to file a supplemental new drug application with the US Food and Drug Administration in 2012. Simultaneously, Roche will file a premarket approval application for a companion test to gauge which NSCLC patients have activating EGFR mutations.

Roche and Astellas, its co-marketing partner for Tarceva, "are collaborating on the development of a PCR-based diagnostic test to identify people with EGFR-activating mutation-positive lung cancer," the spokesperson said. "The diagnostic test will use Roche’s proprietary molecular diagnostic technology to provide a simple tool that will quickly identify EGFR-activating mutations."

Last November, Roche obtained a worldwide sublicense from Genzyme to develop an assay to detect EGFR mutations. Simultaneously, Roche and OSI Pharmaceuticals announced they would work together on developing a PCR-based companion diagnostic to identify NSCLC patients harboring EGFR mutations in their tumors.

Roche obtained a sublicense to develop its own EGFR test after the company signed an out-of-court agreement in May 2010 with Qiagen to settle a disagreement over distribution rights for Qiagen's Therascreen-branded tests kits for EGFR and KRAS mutations. The tests were developed by DxS, which, before being acquired by Qiagen in 2009, signed a deal with Roche granting the company exclusive global distribution rights to the KRAS and EGFR tests in European and certain other non-US markets (PGx Reporter 06/02/2010). Because this case was settled out of court, the terms of the companies' agreement are not known.

Roche's EGFR companion test will run on will run on its Cobas 4800 System, which is already FDA-approved as a diagnostic platform for human papillomavirus, chlamydia, and gonorrhea.

Tarceva is approved in the US as a maintenance treatment for patients with advanced-stage NSCLC that has not advanced after initial treatment with certain chemotherapy agents. The drug is also indicated in the second- and third-line setting to treat advanced NSCLC that has spread after receiving one chemotherapy regimen.

If EU and US health regulators approve Tarceva as a first-line treatment in NSCLC patients with EGFR mutations, this would not restrict Roche from marketing the drug broadly for advanced cancer and in the second- and third-line settings. As such, the approval of Tarceva in this setting would represent the first time a drug firm has used pharmacogenomics to successfully grow the revenues of an already marketed drug.

Tarceva sales in 2010 were 1.3 billion Swiss francs ($1.6 billion), including the drug's indications in lung and pancreatic cancer. It is estimated that between 10 percent and 30 percent of people with advanced NSCLC are EGFR-activating mutation-positive; however the size of the subset differs in Asian and Caucasian populations. Roche estimates that currently approximately 400,000 people with NSCLC, with and without EGFR activating mutations, are using Tarceva.

The sNDA Roche will file with the FDA will include data from the European Randomized Trial of Tarceva vs. Chemotherapy, or EURTAC, study. In this prospective Phase III trial, researchers from the Catalan Institute of Oncology in Barcelona and other institutes screened 1,275 Caucasian NSCLC patients for EGFR mutations between February 2007 and January 2011 and then randomized 174 patients to receive either Tarceva or platinum-based chemotherapy. The researchers used Sanger sequencing followed by Applied Biosystems' TaqMan assay and GeneScan analysis software to identify patients' EGFR mutations.

In the trial ─ data from which was presented at the American Society of Clinical Oncology's annual meeting in June ─ patients with EGFR mutations who received Tarceva experienced progression-free survival for 9.7 months compared to 5.2 months for patients in the chemotherapy arm. Tarceva-treated patients also had a 63 percent reduction in the risk of their cancer progressing compared to those in the chemotherapy arm. The study was stopped early after it met its primary endpoint (PGx Reporter 06/08/2011).

The most common adverse events patients experienced with Tarceva were rash, diarrhea, and elevations in liver enzymes. Serious Grade 3 or 4 adverse events that occurred more often in Tarceva-treated patients than in chemotherapy-treated patients included rash, diarrhea, and alanine transaminase elevation. One patient receiving Tarceva died during the trial.

Following the positive opinion from CHMP, Roche plans to submit efficacy and cost-effectiveness analysis for Tarceva in the EGFR-mutated NSCLC population to UK's National Institute for Health and Clinical Excellence in mid-October. NICE's final recommendation on whether UK's National Health Service should pay for the drug in this patient subset is slated for mid-2012.

"We will be submitting a dossier containing all available data on the clinical and cost-effectiveness of Tarceva in 1L EGFR mutation-positive metastatic NSCLC," the Genentech spokesperson said in an e-mail. "These data focus on randomized clinical trials versus standard first-line chemotherapy (i.e. OPTIMAL and EURTAC), with a particular emphasis on EURTAC as it is the first randomized clinical study of an EGFR TKI completed in a Caucasian population and hence particularly relevant to the UK."

In addition to developing a companion test for Tarceva, Roche plans to apply the Cobas 4800 platform to personalize cancer treatments that are developed internally or by other drug companies. For example, in June Roche said it was developing a companion test that would run on the Cobas 4800 platform to gauge EGFR T790M mutations and determine best responders to a drug being developed by Clovis Oncology, called CO-1686.

Have topics you'd like to see covered in Pharmacogenomics Reporter? Contact the editor at tray [at] genomeweb [.] com.