Erlotinib and Gefitinib Offer Similar Benefit in EGFR-Mutated Non–Small Cell Lung Cancer

“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.


On the Failure of Lung Cancer Drug Onartuzumab in a Phase III Clinical Trial


Most new cancer drugs fail clinical testing. Because they don’t make it to the pharmacy, we usually hear very little about them. But widespread media coverage made it hard to ignore the recent termination of a trial testing the drug onartuzumab. Details of the story raise concerns about the patient enrollment processes of some clinical trials. Continue reading…


Committee: NSCLC Study Should be Halted Due to Lack of Efficacy

“An independent data monitoring committee recommended that a phase 3 study designed to evaluate the combination of onartuzumab and erlotinib in a subset of patients with non–small cell lung cancer be stopped due to lack of clinically meaningful efficacy, according to a press release issued by the drugs’ manufacturer.

“The randomized, multicenter, double-blind, placebo-controlled MetLung study compared the humanized monoclonal antibody onartuzumab (MetMab, Genentech) plus the protein kinase inhibitor erlotinib(Tarceva, Genentech) vs. erlotinib alone in patients with previously treated advanced NSCLC whose tumors were MET-positive.”


Gefitinib, Erlotinib Increased Risk for Interstitial Lung Disease in Patients with Advanced NSCLC

“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.”


NICE to Bar Second-Line Use of Tarceva

“A proposal by (National Health Service) NHS cost regulators to no longer back the second-line use of Tarceva (erlotinib) to treat relapsed non-small cell lung cancer (NSCLC) has angered the drug’s manufacturer Roche and will no doubt come as a shock to patients.

“Following a review of existing guidance, the National Institute for Health and Care Excellence (NICE) has decided that treatment with Tarceva after first-line therapy has failed is no longer a cost-effective option for the NHS.

“According to Roche, the move means that more than 1,000 patients in England and Wales every year will be at risk from being left without an active second-line treatment option.”


Lung Cancer Drug Disappoints in 2 Late-Stage Trials

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.


Lung Cancer Drug BGB324 May Counteract Drug Resistance

The protein Axl has been associated with cell transformation processes that contribute to the spread of cancer through the body and to cancers becoming drug resistant. A recent study investigated the effect of the Axl inhibitor BGB324 on non-small cell lung cancer (NSCLC) cells that had become resistant to EGFR inhibitors like erlotinib (Tarceva). BGB324 restored the effectiveness of EGFR inhibitors against these cancer cells, which had been grown either in a matrix or as tumors in mice. BGB324 also appeared to enhance the effectiveness of the chemotherapy drug docetaxel (Taxotere) and of bevacizumab (Avastin). BGB324 may therefore be a promising new candidate for treating drug-resistant NSCLC. The drug will be tested in a phase Ib clinical trial for NSCLC in 2014.


Rash from Tarceva May Herald Drug Effectiveness

Skin rash is a common side effect of the lung cancer drug erlotinib (Tarceva). However, a clinical trial suggests that this rash can be a good sign and can be used to guide dosing. One hundred twenty-four patients with advanced non-small cell lung cancer (NSCLC) received first-line treatment with Tarceva. The drug dose was gradually increased until patients developed a skin rash or other side effects that prevented further dose increases. Seventy percent of patients developed a skin rash. Patients who developed a skin rash survived longer than those who did not (6.8 months longer on average), even though they did not differ in how much the treatment reduced the growth of their tumors.


Erlotinib, Gefitinib and Vandetanib Inhibit Human Nucleoside Transporters and Protect Cancer Cells from Gemcitabine Cytotoxicity

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.