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FDA approves EGFR mutation detection test for NSCLC drug, Tarceva

Author/Reporter: Ritu Saxena, Ph.D.

The cobas EGFR Mutation Test, Roche Molecular Diagnostics, identifies mutations in epidermal growth factor receptor (EGFR) exons 18, 19, 20 and 21 of patients. The FDA has approved the companion diagnostic for the cancer drug Tarceva (erlotinib). It would select non-small cell lung cancer (NSCLC) patients for treatment with EGFR inhibitors. This is the first FDA-approved companion diagnostic that detects EGFR gene mutations, which are present in approximately 10-30% of non-small cell lung cancers (NSCLC). The test is being approved with an expanded use for Tarceva as a first-line treatment for patients with NSCLC that has metastasized and who have certain mutations in the EGFR gene.

Lung cancer, the leading cause of cancer death among both men and women leads to death of more people than colon, breast, and prostate cancers combined. The American Cancer Society’s most recent estimates for lung cancer in the United States for 2012 reveal that about 226,160 new cases of lung cancer will be diagnosed (116,470 in men and 109,690 in women), and there will be an estimated 160,340 deaths from lung cancer (87,750 in men and 72,590 among women), accounting for about 28% of all cancer deaths. NSCLC is the most common type of lung cancer and usually grows and spreads more slowly than small cell lung cancer. Activating EGFR mutations occur in 10–30% NSCLC cases, and lead to hyperdependence of tumors on EGFR signaling and increased sensitivity of EGFR to inhibition by erlotinib. Genentech/OSI Pharmaceuticals/Roche/Chugai Pharmaceutical’s erlotinib (Tarceva) is a small molecule quinazoline and directly and reversibly inhibits the EGFR tyrosine kinase.

Tarceva has been indicated for first-line treatment of cancer with EGFR mutations including NSCLC. The approval is Tarceva’s fourth indication and the third use for lung cancer. The FDA approved Tarceva on April 16, 2010, for maintenance treatment of patients with locally advanced or metastatic NSCLC whose disease has not progressed after four cycles of platinum-based first-line chemotherapy. Tarceva was originally approved in November 2004 for the treatment of patients with locally advanced or metastatic NSCLC after failure of at least one prior chemotherapy regimen.

In a recent multicenter, open label, randomized, phase III clinical trial (EURTAC trial; NCT0044625; http://clinicaltrials.gov/ct2/show/NCT00446225 ), Tarceva was investigated in patients with advanced NSCLC with mutations in the tyrosine kinase (TK) domain of the EGFR. The EURTAC trial was initiated in February 2007 and completed in December 2012 and enrolled around 174 patients. Patients were divided into two experimental arms. Patients in arm 1 were administered Tarceva (150 mg/day) while patients in arm 2 underwent chemotherapy as platinum-based doublets. The chemotherapeutic drugs were administered as Cisplatin (75 mg/m²) / Docetaxel (75 mg/m²); Cisplatin (75 mg/m²) / Gemcitabine (1250 mg/m²; day 1 and 8); Docetaxel (75 mg/m²) /carboplatin (AUC=6); Gemcitabine (1000 mg/m²; day 1 and 8) / Carboplatin (AUC=5). Results revealed that Erlotinib is better tolerated in Chinese population (grade 3-4 toxicities 17%) then in European patients (grade 3-4 toxicities 45%). Erlotinib scored significantly better than chemotherapy in terms of progression-free survival (PFS) with 9.7 versus 5.2 months, respectively (HR 0.37, 95% CI 0.25-0.54). Thus, the results of the trial strengthen the rationale for routine baseline tissue-based assessment of EGFR mutations in patients with NSCLC and for treatment of mutation-positive patients with EGFR tyrosine-kinase inhibitors. (Gridelli C and Rossi A, J Thorac Dis. 2012 Apr 1;4(2):219-20; http://www.ncbi.nlm.nih.gov/pubmed/22833832 )

In conclusion, FDA approval of cobas EGFR Mutation Test is a recent example of how genotyping patients in clinical trials could lead to crucial information regarding personalizing the diagnostic and therapeutic approaches.

Reference:

News brief

Clinical lab products http://www.clpmag.com/all-news/24074-fda-approves-first-companion-diagnostic-to-detect-gene-mutation-linked-with-a-type-of-lung-cancer

Clinical trial http://clinicaltrials.gov/ct2/show/NCT00446225

Research articles

Melosky B. EURTAC first line therapy for non small cell lung carcinoma in epidermal growth factor receptor mutation positive patients: A choice between two TKIs. J Thorac Dis. 2012 Apr 1;4(2):221-2; http://www.ncbi.nlm.nih.gov/pubmed/22833833

Gridelli C and Rossi AJ. EURTAC first-line phase III randomized study in advanced non-small cell lung cancer: Erlotinib works also in European population. Thorac Dis. 2012 Apr 1;4(2):219-20; http://www.ncbi.nlm.nih.gov/pubmed/22833832

Related reading

Nguyen KS and Neal JW. First-line treatment of EGFR-mutant non-small-cell lung cancer: the role of erlotinib and other tyrosine kinase inhibitors. Biologics. 2012;6:337-45; http://www.ncbi.nlm.nih.gov/pubmed/23055691

http://pharmaceuticalintelligence.com/2012/11/06/non-small-cell-lung-cancer-drugs-where-does-the-future-lie/ Curator: Ritu Saxena, Ph.D.

http://pharmaceuticalintelligence.com/2013/03/03/personalized-medicine-in-nsclc/ Curator: Larry H. Bernstein, M.D.

http://pharmaceuticalintelligence.com/2012/11/08/lung-cancer-nsclc-drug-administration-and-nanotechnology/ Author: Tilda Barliya, Ph.D.

http://pharmaceuticalintelligence.com/2012/09/18/personalized-rx-decisions-in-nsclc-treatments-symposium-in-thoracic-oncology/ Reporter: Aviva Lev-Ari, Ph.D., R.N.

http://pharmaceuticalintelligence.com/2013/05/15/diagnosis-of-cardiovascular-disease-treatment-and-prevention-current-predicted-cost-of-care-and-the-promise-of-individualized-medicine-using-clinical-decision-support-systems/ Author/Curator: Larry H. Bernstein, M.D.