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.
“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.”
EGFR inhibitors like erlotinib (Tarceva) are highly effective for most patients with non-small cell lung cancer (NSCLC) who have mutations in the EGFR gene. However, results from the TAILOR clinical trial suggest that, in patients without EGFR mutations (who have so-called EGFR wild-type NSCLC), EGFR inhibitors may be less effective than chemotherapy as second-line treatment. Patients with advanced wild-type NSCLC who had previously been treated with platinum-based chemotherapy were given either Tarceva or the chemotherapy agent docetaxel (Taxotere). Average survival in the Taxotere-treated group (8.2 months) was longer than in the Tarceva group (5.4 months).
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.
“TO THE EDITOR: Laurie et al recently published a review article in Journal of Clinical Oncology on the role of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) in patients with EGFR wild-type (WT) non–small-cell lung cancer (NSCLC). The authors clearly stated that the majority of patients have a WT phenotype; therefore, the treatment of this molecular subgroup represents a relevant issue. At present, all indirect data suggest a superiority of chemotherapy (CT) over TKIs in all settings in patients with EGFR WT disease, at least for progression-free survival (PFS).”
Funding represents a decisive barrier to the nationwide implementation of genetic testing for a key lung cancer mutation in Canada, a recent study finds. Patients with non-small cell lung cancer (NSCLC) who have a mutation in the EGFR gene frequently benefit from treatment with EGFR inhibitors. AstraZeneca, makers of the EGFR inhibitor gefinitinb (Iressa), reimbursed Canadian laboratories for offering EGFR mutation testing to patients with advanced non-squamous NSCLC for 12 months. EGFR mutation testing was rapidly adopted into routine clinical practice in Canada. However, testing rates dropped sharply once the reimbursement program ended. Researchers conclude that a national strategy is needed to provide resources for continued EGFR testing.
Results from the FASTACT clinical trial suggest that interspersing erlotinib (Tarceva) among rounds of chemotherapy improves outcomes in non-small cell lung cancer (NSCLC). Patients with advanced NSCLC received six cycles of gemcitabine (Gemzar) plus carboplatin (Paraplatin) or cisplatin (Platinol), with Tarceva added during the second half of each chemotherapy cycle. This regimen prolonged time without cancer worsening and increased survival compared to patients who had received chemotherapy and placebo, though the benefit was only seen in patients with mutations in the EGFR gene. This approach may be most useful for patients whose EGFR status is unknown, as patients with known EGFR mutations may be even better served by first-line treatment with Tarceva alone.
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.