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Roche Receives FDA Nod for New PGx Indication for Tarceva in Metastatic NSCLC with Companion Dx

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Roche has received US Food and Drug Administration approval for a new pharmacogenetic indication for the non-small cell lung cancer drug Tarceva (erlotinib) and a companion test that picks out best responders to the treatment.

The agency announced this week that it had approved Roche's Cobas EGFR Mutation test as a companion diagnostic for Tarceva when it is given as a first-line treatment for metastatic NSCLC patients whose tumors harbor certain EGFR mutations.

Roche and subsidiary Genentech will continue to sell Tarceva for this new indication at the monthly wholesale cost of $5,800, which amounts to nearly $70,000 for one year. The EGFR companion test will be billed through a standard CPT code and pricing "is determined by the laboratory based on the test volume and contract framework established with the laboratory," a Genentech spokesperson told PGx Reporter. "Pricing is in line with anticipated reimbursement guidelines."

According to pricing guidelines issued by Medicare contractor Palmetto GBA, a genetic test that gauges common EGFR variants in NSCLC patients is reimbursed at $225.

In granting approval for the drug/test combination, the FDA reviewed data from the Phase III EURTAC study. In that trial, Roche was able to show that its RT-PCR-based Cobas test was able to gauge which patients' tumors harbored deletions in exon 19 and L858R substitution mutations in exon 21. NSCLC patients with these EGFR mutations when treated with Tarceva lived without their disease progressing for an average for 10.4 months compared to those who received a standard combination chemotherapy regimen and lived for 5.4 months without their cancer progressing.

Patients treated with Tarceva in the trial most frequently experienced diarrhea, weakness, rash, cough, shortness of breath, and decreased appetite. Rash and diarrhea were the most frequent serious adverse reactions in Tarceva-treated patients.

Although doctors can still prescribe Tarceva to advanced NSCLC patients who don't harbor EGFR mutations as maintenance therapy or as second- or third-line treatment, when administered as the first-line defense for those with metastatic disease, the drug can only be given to those with EGFR exon 19 deletions or exon 21 L858R substitution mutations "as detected by an FDA-approved test," the drug's label states.

Roche's FDA-approved companion test will be entering a market where hospitals and labs already perform other lab-developed tests that gauge the same EGFR mutations, but don't have the agency's clearance. When launching its BRAF companion test for the melanoma drug Zelboraf, Roche had difficulty convincing test providers to transition from their existing LDTs to the FDA-approved test, given that such a transition requires additional investments (PGx Reporter 9/28/2011).

But those customers who previously adopted the Cobas BRAF test, may not need too much convincing to adopt the EGFR test, making its launch comparatively smoother. "One advantage we have with the EGFR launch is our existing customer base currently testing with the Cobas BRAF assay. We expect these labs to quickly convert to the FDA-approved Cobas EGFR test due to the similar workflow and the positive experience of a reliable and robust performance from the Cobas BRAF assay," the Genentech spokesperson said. "Additionally, labs are wanting to consolidate as many tests as possible on one platform to maximize the usage in their lab."

Roche currently has contracts with three commercial labs that will perform the Cobas EGFR test to gauge best responders to Tarceva: Clarient in Aliso Viejo, Calif.; Laboratory Corporation of America in Research Triangle Park, NC; and Carolinas Medical Center in Charlotte, NC. "Samples can be sent to these sites for testing until the test is more widely available," the Genentech spokesperson noted.

In approving the drug/diagnostic combination, the FDA highlighted that Roche's Cobas test was the first companion diagnostic that gauges EGFR mutations to receive a nod from the agency. Astellas, which markets Tarceva in the US with Roche subsidiary Genentech, announced in January that it had submitted a supplemental NDA for Tarceva for first-line treatment of NSCLC and that Roche had also submitted a companion EGFR mutation test to pick out best responders to the drug. The FDA had granted priority review status to the sNDA for Tarceva.

The European Commission two years ago issued a positive decision for Tarceva as a treatment for EGFR-mutated NSCLC. In the US, the latest approval represents the fourth indication for the drug.

Tarceva was first approved by the FDA in 2004 as a treatment for locally advanced or metastatic NSCLC after patients had failed to respond to at least one chemo regimen. In 2010, the drug was approved as a maintenance therapy for those with locally advanced or metastatic NSCLC who had not progressed after four cycles of platinum-based, first-line chemo. Tarceva is also approved for advanced pancreatic cancer.

Last year, Tarceva had global sales of 1.3 billion Swiss Francs ($1.3 billion), to which US sales contributed 571 million Swiss Francs. With the new PGx indication, "more patients across all lines of therapy have access to Tarceva," Sef Kurstjens, Astellas' chief medical officer, said in a statement.

According to National Cancer Institute estimates, there will be more than 228,000 new cases of lung cancer this year, and nearly 160,000 deaths. Approximately 85 percent of lung cancers are of the NSCLC variety and EGFR mutations occur in between 10 percent and 15 percent of advanced NSCLC tumors, or in approximately 13,000 to 20,000 patients.

The new PGx indication for Tarceva comes as professional societies are recognizing the need to broadly test lung cancer patients and gauge whether they harbor mutations that will hinder their response to treatment. In April, the College of American Pathologists, the International Association for the Study of Lung Cancer, and the Association for Molecular Pathology released guidelines recommending that all patients with advanced lung adenocarcinomas should be tested for alterations in EGFR and ALK genes to determine if they will benefit from certain tyrosine kinase inhibitors, such as Tarceva (PGx Reporter 4/10/2013).

Boehringer Ingelheim also is developing a NSCLC drug in patients with EGFR mutated tumors, called afatinib. The company is working with Qiagen to develop the companion EGFR test for that drug. In the LUX-Lung 3 trial, patients with EGFR-positive tumors who received afatinib lived for a median of 11.1 months without their cancer progressing, compared to 6.9 months for those treated with a standard chemotherapy regimen (PGx Reporter 6/6/2012).

Toward the end of last year, Boehringer and Qiagen submitted applications to the FDA for the approval of afatinib and its companion test. Afatinib was granted priority review by the FDA, and the companies are expecting to hear from FDA about their drug/test combination product in July.

Once on the market, afatinib will compete with Tarceva as another PGx treatment option for NSCLC patients. However, afatinib is distinguished from first-generation EGFR inhibitors such as Tarceva and Iressa (gefitinib) in that it is an irreversible inhibitor, and as such, Boehringer is hoping that the drug will be more effective than these earlier products. Afatinib covalently binds to EGFR, HER2, and HER4 receptors that are overexpressed in certain cancers. Once the drug permanently attaches to the cell receptors, it blocks these receptors and inhibits cell signaling pathways that cause tumor cells to proliferate.

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