On July 12, the FDA announced that it had approved the targeted therapy afatinib (Gilotrif) for the treatment of metastatic non-small cell lung cancer (NSCLC) with mutations in the epidermal growth factor receptor (EGFR) gene.
EGFR mutations occur in about 10 to 15 percent of all NSCLC patients. The overexpression of the EGFR protein caused by the mutation leads to rapid cell division in tumors. Prior to the approval of afatinib, patients in the United States could only take erlotinib (Tarceva) to combat the EGFR mutation. The third major drug available to treat EGFR-mutated tumors, gefitinib (Iressa) has not yet been approved by the United States but is readily available in many other countries. Erlotinib has consistently outperformed gefitinib, so its lack of availability in the U.S. is no huge loss.
The approval of afatinib provides U.S. patients with a second method to constrain tumor growth. Though erlotinib has proven to be effective in relieving symptoms and improving survival, the effect is unfortunately only temporary. After about a year, the tumor develops resistance to the drug, and symptoms reappear as the cancer begins to progress again. Researchers hope that strong positive results from afatinib’s clinical trials indicate the same won’t be true of this targeted therapy as well.
In the international LUX-Lung 3 study, hailed by many researchers as the most robust phase III clinical trial ever in EGFR-mutated lung cancer patients, afatinib significantly outperformed standard chemotherapy treatment. The trial included 345 patients, all with stage 3 or stage 4 EGFR-mutated lung cancer and no prior chemotherapy treatment. Two-thirds of the patients received 40 mg of afatinib daily, while the remaining patients underwent a chemotherapy regimen of cisplatin and pemetrexed every 21 days for up to six cycles. The results were quite clear: afatinib extended progression-free survival by 11.1 months, compared to just 6.9 months for chemotherapy.
The resounding success of the clinical trial convinced the FDA to grant afatinib “breakthrough therapy” status. Drugs awarded this designation are essentially fast-tracked toward approval, with an expedited review process before a final decision is announced.
Also on July 12, the FDA approved a diagnostic test, therascreen, which will be used to help doctors determine whether a lung cancer patient’s tumor has the EGFR mutation. Therascreen, a product of Qiagen, proved its validity during the LUX-Lung 3 study.
Additional research presented before the approval indicated that afatinib might also be beneficial when administered as a combined therapy in conjunction with cetuximab (Erbitux) for patients who have already become resistant to erlotinib.
Another clinical trial, LUX-Lung 7, is currently underway to compare afatinib and gefitinib head-to-head, and may have results available in two years. Cross-trial comparisons, though not typically used in making treatment decisions, seem to give an advantage to afatinib.
At the end of the day, approval of afatinib means that NSCLC patients with EGFR mutations around the world, but particularly in the United States, have a new, potentially powerful drug to aid them in their battle against lung cancer. Time will tell if it becomes more effective and more recommended than erlotinib and gefitinib.