Phase II Trial of Efatutazone Shows Challenge of Matching Treatment to Population

“Work at the University of Colorado Cancer Center led to phase II trial of efatutazone with erlotinib in patients with refractory non-small cell lung cancer. Results are reported today at the American Association for Cancer Research (AACR) Annual Meeting 2014. While efatutazone did not improve the efficacy of erlotinib in this trial, researchers hope lessons from the trial will allow them to make better future use of the drug or other drugs in its class.

” ‘In oncology and especially in lung cancer, everything is personalized. We’re exploring different molecular markers that identify which drugs are for the right patient. After this phase II trial, we’re working to find the right biomarker that could help us discover who is most likely to respond to efatutazone. This trial was done in an unselected population. But if we had the right population with the right marker, we hope that we could find a meaningful effect,’ says Ana Oton, MD, investigator at the CU Cancer Center, Associate Professor of Medical Oncology at the University of Colorado School of Medicine, and the study’s first author.”

Editor’s note: This trial tested a treatment without the use of molecular testing to see which patients might have benefited. This is a problem in the design of many clinical trials, as our Chief Scientist explains here. For future testing of the treatment the scientists hope to identify a molecular test that will help them select patients who are more likely to benefit.

Roche Lung Cancer Pill Gets Reprieve in UK Reversal

“Britain’s health cost watchdog NICE on Friday reversed an earlier decision to limit the use of Roche’s Tarceva cancer pill on the state health service in a move the drugmaker said would help around 2,000 patients a year.

“New draft guidance from the National Institute for Health and Clinical Excellence (NICE) now backs use of Tarceva for people with non-small-cell lung cancer that has progressed after chemotherapy in wider circumstances than originally suggested.”

ELCC 2014 News: Efficacy and Safety of Targeted Therapy in Elderly Patients With Lung Cancer Adenocarcinoma

“Clinical records of elderly patients with non-small-cell lung cancer (NSCLC) show that treatment with bevacizumab seems to be safe and effective in patients with controlled pre-existing cardiovascular disease and good performance status. Furthermore, another targeted agent, erlotinib, represents a valuable treatment option in elderly NSCLC patients with co-morbidities, especially if they harbour EGFR mutations. The data were presented by Prof. Kostas Syrigos on behalf of colleagues from the Oncology Unit, Sotiria General Hospital, Athens School of Medicine, Athens, Greece in a general poster session at the 4th European Lung Cancer Conference (26-29 March 2014, Geneva, Switzerland).”

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.