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FDA approves Gilotrif for late-stage NSCLC
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The FDA today approved afatinib for treatment of patients with metastatic non–small lung cancer whose tumors express certain types of epidermal growth factor receptor gene mutations.
Afatinib (Gilotrif, Boehringer Ingelheim) — a tyrosine kinase inhibitor — is indicated for patients whose tumors express exon 19 deletions or exon 21 L858R substitution, the two most common EGFR gene mutations found in NSCLC.
The FDA approved afatinib concurrently with the therascreen EGFR RGO PCR Kit, a companion diagnostic that can help identify EGFR mutations in lung cancer.
“Today’s approvals further illustrate how a greater understanding of the underlying molecular pathways of a disease can lead to the development of targeted treatments,” Richard Pazdur, MD, director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research, said in a press release.
Afatinib is the second drug to receive FDA approval this year for treatment of metastatic NSCLC with exon 19 deletions or exon 21 L858R substitution. In May, the FDA approved erlotinib (Tarceva; Genentech, Astellas Pharma) along with the cobas EGFR Mutation Test, another companion diagnostic designed to identify patients with EGFR gene mutations.
The FDA approved afatinib under its priority review program.
The approval was based in part on results of a trial that included 345 patients with metastatic NSCLC whose tumors expressed EGFR mutations. Researchers randomly assigned patients to receive afatinib or up to six cycles of chemotherapy with pemetrexed and cisplatin.
Study results showed afatinib extended PFS by 4.2 months compared with chemotherapy. Researchers reported no statistically significant difference in OS between the two arms.
Common side effects reported in the afatinib arm included dry skin, itching, diarrhea, inflammation of the mouth, bladder inflammation, runny nose, fever, eye inflammation and hypokalemia.
The FDA approval of the therascreen test was based on the same study, as tumor samples helped validate the test's ability to detect EGFR mutations.
Perspective
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Eric H. Bernicker, MD
The data on which this approval was based — presented at the ASCO Annual Meeting in 2012 — confirm afatinib is a very effective medication. Better yet, it comes with very manageable toxicities.
Patients with EGFR driver mutations now have a number of options. We're not curing people yet, and we need to keep moving forward, but this is a very exciting development.
For many years in lung cancer, unfortunately, we had very marginal benefits from several of our therapies. There is a growing sense of optimism due to the potential of specific targeted therapies, whether its afatinib or erlotinib for EGFR-positive tumors or crizotinib for ALK-mutated tumors. We also have immunotherapy on the horizon.
We've come a long way, thankfully. Even though we still have a long way to go, there is a feeling that we're turning a significant corner and that we're going to eventually make significant overall impacts on survival. This is the most exciting time that we've had treating advanced lung cancer in many years, and hopefully the future remains bright.
Perspective
Back to TopNathan Pennell, MD, PhD
Patients with advanced non–small cell lung cancer whose tumors harbor mutations in the epidermal growth factor receptor (EGFR) gene — comprising about 10% of lung cancer cases — received good news when the FDA approved afatinib for first-line treatment in this population.
Afatinib, an irreversible pan-human epidermal growth factor receptor (HER) family tyrosine kinase inhibitor, was approved based on results of the LUX-Lung 3 trial, which compared afatinib with cisplatin and pemetrexed chemotherapy in previously untreated EGFR-mutant NSCLC patients (Sequist LV. J Clin Oncol. 2013;Published online ahead of print July 1). Afatinib was shown to have a response rate and PFS more than double that of chemotherapy in this population. Although there was no difference in OS between the arms, patient-reported outcomes were significantly better with afatinib, likely because of the high rate and rapidity of responses along with a more favorable side-effect profile compared with chemotherapy.
Afatinib is the second drug approved for the EGFR-mutant NSCLC population this year. Erlotinib received this designation in May. Both drugs are only approved for patients with the most common exon 19 deletion and exon 21 (L858R) substitution, which make up 90% of sensitizing mutations. Both drugs have a similar spectrum of side effects, with high rates of acneiform skin rash and diarrhea (although somewhat more common with afatinib). Afatinib also seems to have higher rates of stomatitis and paronychia.
It is now clear that EGFR tyrosine kinase inhibitors are highly effective and represent the standard of care for patients with EGFR-mutation–positive NSCLC, but which one should you pick? Afatinib is the new kid on the block, whereas erlotinib has been widely used off-label in this population for years.
There is no head to head comparison, although a trial is planned. Both have shown superior outcomes compared with conventional chemotherapy, with similar response rates and PFS (Rosell R. Lancet Oncol. 2012;13:239-246). Given the somewhat higher rates of serious side effects with afatinib, erlotinib will probably remain the more commonly used drug in this space until there is reason to believe one is more effective than the other.
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