New Drugs Aim to Defeat Tumor Resistance to EGFR Inhibitors


In recent years, many people with non-small cell lung cancer (NSCLC) have been successfully treated with drugs called EGFR inhibitors. But over time, most patients develop resistance, and the drugs stop working. Researchers are hard at work developing new drugs to help patients who can no longer be treated with EGFR inhibitors.

EGFR inhibitors get their name from a gene called EGFR. Many lung cancer tumors have mutations in this gene. These mutations convert EGFR from a normal gene into a cancer gene that initiates and promotes cancer growth. Approximately 10% to 15% of white and 30% to 35% of Asian patients with NSCLC have EGFR mutations. Continue reading…


At ASCO, Next-Gen EGFR Inhibitors Show Early Promise in Lung Cancer Patients with T790M Mutations

“Next-generation EGFR inhibitors for treating metastatic non-small cell lung cancer patients who have acquired resistance to first-generation drugs in this class accurately hit mutant EGFR tumor cells and caused fewer serious side effects, early data presented at a major cancer conference showed.

“Researchers at the American Society of Clinical Oncology’s annual meeting here this week, presented preliminary data from human studies on three next-generation EGFR inhibitors: AstraZeneca’s AZD9291, Clovis Oncology’s CO-1686, and Hanmi Pharmaceutical’s HM61713. All three agents showed promising activity against patients who had EGFR mutations, had received prior treatment with a first-generation tyrosine kinase inhibitor – such as Roche’s Tarceva (erlotinib) and AstraZeneca’s Iressa (gefinitib) – and had T790M mutations.”

Editor’s note: For a more reader-friendly explanation of these new drugs, check out the “Drug resistance” section of our Chief Scientist’s latest blog post.


ASCO 2014 Lung Cancer Roundup


Every year, thousands of people gather in Chicago, Illinois, for the American Society of Clinical Oncology (ASCO) Annual Meeting. The largest meeting of its kind, ASCO brings together doctors, researchers, nurses, patient advocates, pharmaceutical company representatives, and more to discuss the latest in cancer research. Here are some of the most exciting new developments in lung cancer research presented last week at ASCO 2014: Continue reading…


AstraZeneca Seeking to Get Cancer Drugs to Patients Early

“British patients could benefit from AstraZeneca’s promising new cancer drugs well before they complete clinical testing, the Telegraph can reveal.

“Pascal Soriot, chief executive, told the Telegraph he was looking to make two of Astra’s most eye-catching cancer drugs widely available to patients as soon as possible.

“Britain’s recently launched early access to medicines scheme, which aims to get drugs to patients years earlier than the normal regulatory process allows, is among the programmes in Mr Soriot’s sights. The US, France and Japan have also established pathways to fast-track promising new drugs to patients ahead of final regulatory approval.”


Thwarting Drug Resistance in Lung Cancer


If you’ve read up on lung cancer research in the last few years, you probably know that large strides have been made in targeted therapies for non-small cell lung cancer (NSCLC). Targeted therapies are drugs that identify and attack specific mutated proteins that are detected in tumors. Because noncancerous cells do not have these specific mutations, targeted therapies can make a beeline for cancer, while leaving healthy tissue unharmed. Continue reading…


New EGFR Inhibitor AZD9291 Shows Promising Activity in Treatment-Resistant Non–Small Cell Lung Cancer

“Findings from a phase I study of a new mutant-selective epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, AZD9291, point to a promising new treatment option for patients with advanced, EGFR-mutant, non–small cell lung cancer (NSCLC) that is resistant to standard EGFR inhibitors. Roughly 50% of patients experienced tumor shrinkage, and the drug worked particularly well in patients with the T790M mutation (detected in 60% of patients), which causes the most common form of EGFR therapy resistance. The study was presented at a presscast in advance of the 2014 ASCO Annual Meeting (Abstract 8009^).”

Editor’s note: This story is about a new targeted therapy drug called AZD9291 that is designed to attack tumors with a mutation in the EGFR gene, as detected by molecular testing. In particular, it is designed for patients who are resistant to other so-called EGFR inhibitors as a result of developing a particular EGFR mutation known as T790M. In a clinical trial to test the drug in patients, it was found to show promising results for patients with advanced non-small cell lung cancer (NSCLC) with EGFR mutations, and even better results in patients with the T790M mutation.


New Drug May Offer Option for Lung Cancer Patients Resistant to Tarceva/Iressa

Drugs known as EGFR inhibitors—like erlotinib (Tarceva) and gefitinib (Iressa)—are used to treat non-small cell lung cancer (NSCLC) with so-called ‘activating mutations’ in the EGFR gene. Unfortunately, drug resistance develops relatively quickly in most patients. Resistance is often due to additional EGFR mutations, so-called ‘resistance mutations,’ such as EGFR T790M. Researcher have developed a new EGFR inhibitor, AZD9291, which targets both activating and resistance mutant forms of EGFR. AZD9291 inhibited the growth of EGFR-mutant NSCLC cell cultures and eradicated lung cancer tumors with either activating or resistance mutations in mice. Because AZD9291 is less active against normal, non-mutant EGFR, it may have fewer side effects than other EGFR inhibitors. Initial tests of AZD9291 in patients have been promising.


Potential New Drug for Some Patients With Treatment-Resistant Lung Cancer

The investigational drug AZD9291, a third-generation EGFR inhibitor, showed promise in preclinical studies and provides hope for patients with advanced lung cancers that have become resistant to existing EGFR inhibitors, according to results presented here at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics, held Oct. 19-23.


First T790M Inhibitor Shows Promise in Early Lung Cancer Trial

Researchers may finally have found a treatment for a type of non-small cell lung cancer (NSCLC) that resists currently available therapies, according results presented at the 2013 European Cancer Congress in Amsterdam, Netherlands. These resistant NSCLCs have an EGFR mutation called T790M, which is more common in Asian people; the experimental treatment is a T790M inhibitor called AZD9291. In an ongoing phase I clinical trial that included 12 people with lung cancers that had the T790M mutation, tumors shrank in more than half. This trial is currently enrolling new patients.