“A retrospective study has shown that two targeted therapy drugs—erlotinib (Tarceva) and gefitinib (Iressa)—achieved similar outcomes among people with metastatic or recurrent non–small cell lung cancer (NSCLC) harboring an EGFR mutation. These EGFR tyrosine kinase inhibitors have previously been reported to offer benefit over standard chemotherapy as first-line treatment of EGFR-positive advanced NSCLC. The study findings by Lim et al are published in the Journal of Thoracic Oncology.
“Erlotinib is used worldwide, and gefitinib is widely used in Asian countries and recently in Europe (only for patients with tumors harboring EGFR mutations) but not in the United States. Indirect comparisons of the two agents have resulted in inconsistency with regard to progression-free survival, and until now, the agents have not been compared head-to-head in patients with EGFR-positive NSCLC.”
Editor’s note: Erlotinib and gefitinib are targeted therapies. Learn more.
“Patients treated with advanced non–small cell lung cancer treated with gefitinib and erlotinib demonstrated a significant increased risk for all-grade and fatal interstitial lung disease events, according to results of a systematic review and meta-analysis.
“Erlotinib (Tarceva, Genentech) and gefitinib (Iressa, AstraZeneca), both of which are oral epidermal growth factor receptor tyrosine kinase inhibitors, are commonly used during treatment of advanced NSCLC. However, the overall risk for interstitial lung disease events are not known.”
In a recent phase III clinical trial, the cancer drug dacomitinib was no more effective than a placebo at prolonging survival for patients with advanced non-small cell lung cancer (NSCLC) for whom standard therapy had failed. Like the targeted drugs erlotinib (Tarceva) and gefitinib (Iressa), dacomitinib blocks the protein EGFR, but it also inhibits a number of similar, related proteins. Another trial compared dacomitinib to Tarceva in NSCLC patients who had previously received at least one EGFR inhibitor. Dacomitinib did not increase time without cancer worsening compared to Tarceva. Results from a third phase III trial, which compares dacomitinib to Iressa in NSCLC patients with EGFR mutations, are expected next year.
Damaraju VL, Scriver T, Mowles D, Kuzma M, et al. Clinical Cancer Research. Oct 29, 2013.
Combinations of tyrosine kinase inhibitors (TKIs) with gemcitabine have been attempted with little added benefit to patients. We hypothesized that TKIs designed to bind to ATP binding pockets of growth factor receptors also bind to transporter proteins that recognize nucleosides.
Vandetanib inhibited hENT1, hENT2, hCNT1, hCNT2 and hCNT3 whereas erlotinib inhibited hENT1 and hCNT3 and gefitinib inhibited hENT1 and hCNT1. The potential for reduced accumulation of nucleoside chemotherapy drugs in tumor tissues due to inhibition of hENTs and/or hCNTs by TKIs indicates that pharmacokinetic properties of these agents must be considered when scheduling TKIs and nucleoside chemotherapy in combination.
A molecule named Mig 6 may help predict how much a patient will benefit from EGFR inhibitors like Tarceva (erlotinib) or Iressa (gefitinib). Preliminary results from an ongoing study reveal that cancer cells that are resistant to EGFR inhibitors have high Mig 6 levels. In an animal model of non-small cell lung cancer (NSCLC) without EGFR mutations, higher Mig 6 levels predicted more resistance to EGFR inhibitor treatment. Finally, NSCLC patients with low Mig 6 levels were more likely to survive for over a year after EGFR inhibitor treatments. Mig 6 may help identify patients who would most benefit from EGFR inhibitors.
A clinical trial investigating whether the cancer drug gefinitib (Iressa) can improve outcomes after lung cancer surgery has been ended early. The trial followed patients who were given either Iressa or a placebo after receiving surgery to completely remove their non-small cell lung cancer (NSCLC). When two other studies showed no benefit of Iressa in similar disease situations, the trial was terminated. Due to the early termination of the trial, no firm conclusions can be drawn from the results. However, analysis of the already collected data suggests that Iressa likely did not improve survival, or delay cancer recurrence in this patient population, and may have indeed been harmful.
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.
Shi Y, Zhang L, Liu X, Zhou C, et al. The Lancet Oncology. Sept, 2013.
Icotinib, an oral EGFR tyrosine kinase inhibitor, had shown antitumour activity and favourable toxicity in early-phase clinical trials. We aimed to investigate whether icotinib is non-inferior to gefitinib in patients with non-small-cell lung cancer. Icotinib could be a new treatment option for pretreated patients with advanced non-small-cell lung cancer.