“UK drugs watchdog the National Institute for Health and care Excellence (NICE) this morning issued new draft guidance recommending German family-owned drug major Boehringer Ingelheim’s Giotrif (afatinib) as an option for treating locally-advanced or metastatic non-small-cell lung cancer (NSCLC) in people whose tumors test positive for the EGFR-TK mutation and have not received a EGFR-TK inhibitor.”
Editor’s Note: In the US, this drug is called Gilotrif. It is meant for patients whose tumors have a mutation in the EGFR gene, as detected by molecular testing. Learn more about molecular testing to guide treatment decisions.
Afatinib (Gilotrif) is a new lung cancer drug for people with non-small cell lung cancer (NSCLC) who have mutations in the EGFR gene. The LUX-Lung 3 clinical trial demonstrated that Gilotrif is superior to chemotherapy as first-line treatment in a global population of patients with EGFR-mutant NSCLC. The LUX-Lung 6 trial confirmed these findings specifically in an Asian population; Asia has a three times higher rate of EGFR-mutant NSCLC than Western countries. More recent evidence indicates that Gilotrif is as effective in patients with rare EGFR mutations as it is in those with common mutations. Finally, Gilotrif recently showed effectiveness in NSCLC patients whose cancer had spread to the brain.
No more trials comparing EGFR inhibitors to chemotherapy in patients with non-small cell lung cancer (NSCLC) should be conducted, argues an editorial by cancer researcher Corey Langer. Eight separate trials have found that EGFR inhibitors like erlotinib (Tarceva), gefitinib (Iressa), and afatinib (Gilotrif) produce better results than chemotherapy in NSCLC patients who have mutations in the EGFR gene. No further confirmation is needed, Langer contends. Instead, research should focus on ways to overcome the drug resistance that many patients eventually develop to EGFR inhibitors, meaningfully extending overall survival in NSCLC, and directly comparing the relative effectiveness and safety of Tarceva, Iressa, and Gilotrif.
Langer CJ. Journal of Clinical Oncology. Aug 26, 2013.
“In the last decade we have witnessed a major evolution in both molecular diagnostics and individualized therapy in the management of advanced non–small-cell lung cancer (NSCLC). The identiﬁcation of epidermal growth factor receptor (EGFR) mutation and the centrality of EGFR tyrosine kinase inhibitors (TKIs) in patients whose tumors harbor these mutations have irrevocably altered how we view NSCLC. The more recent recognition of echinoderm microtubule-associated protein-like 4/anaplastic lymphoma kinase and ROS1 translocations as molecular drivers, for which speciﬁc treatment exists, has altered our perspective still more. NSCLC is no longer considered a monolithic illness, but it is now readily recognized as a constellation of genotypic entities for which targeted therapy has an increasing role. In this regard, despite clinical, radiographic, and even histologic similarities from tumor to tumor, the genotypic footprint, one believes, should ultimately trump phenotype when it comes to therapeutic decision making.”
Afatinib (Gilotrif), a new drug for the treatment of some lung cancers, will become commercially available in the U.S. beginning the week of September 2. Gilotrif is approved as a first-line treatment for patients with advanced non-small cell lung cancer (NSCLC) who have certain mutations in the EGFR gene. A companion diagnostic, the therascreen EGFR RGQ PCR Kit, can detect these specific EGFR mutations, so-called exon 19 deletions or exon 21 (L858R) substitutions. The makers of the drug will offer a patient support program to provide financial and other support to help patients who might otherwise not have access to Gilotrif.
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. Continue reading…
Food and Drug Administration (FDA) | July 12, 2013
Based on the positive results of a recent clinical trial, the FDA approved afatinib for first-line treatment of patients with late-stage, non-small cell lung cancer (NSCLC) who have a mutation in the EGFR gene. The drug, which will be marketed under the name Gilotrif, is specifically intended for patients with two particular EGFR mutations: exon 19 deletion and exon 21 L858R substitution. The FDA also approved the therascreen EGFR RGQ PCR Kit, a companion diagnostic used to test for EGFR mutations. Afatinib differs from other EGFR inhibitors like erlotinib (Tarceva) and gefitinib (Iressa) in that it irreversibly destroys the EGFR protein, instead of just reversibly blocking it, and also inhibits several other related proteins.
Results from the LUX-Lung 3 clinical trial show that afatinib appears to be well tolerated and more effective than chemotherapy in patients with advanced non-small cell lung cancer (NSCLC) who have a mutation in the EGFR gene. Afatinib produced higher response rates and longer periods without cancer progression than cisplatin (Platinol) plus pemetrexed (Alimta), suggesting that it could be considered as a first-line therapy in advanced EGFR-mutant NSCLC. Afatinib, which is under priority review for approval by the FDA, may be effective in patients resistant to other EGFR inhibitors like erlotinib (Tarceva) and gefitinib (Iressa). However, no trials so far have directly compared afatinib with Tarceva or Iressa.
Sequist LV, Yang JC, Yamamoto N, O'Byrne K, et al. J Clin Oncol. Jun 25, 2013.
The LUX-Lung 3 study investigated the efficacy of chemotherapy compared with afatinib, a selective, orally bioavailable ErbB family blocker that irreversibly blocks signaling from epidermal growth factor receptor (EGFR/ErbB1), human epidermal growth factor receptor 2 (HER2/ErbB2), and ErbB4 and has wide-spectrum preclinical activity against EGFR mutations. A phase II study of afatinib in EGFR mutation–positive lung adenocarcinoma demonstrated high response rates and progression-free survival (PFS).
In this phase III study, it was found that afatinib is associated with prolongation of PFS when compared with standard doublet chemotherapy in patients with advanced lung adenocarcinoma and EGFR mutations.