Ros1 Gene Fusions Found in 2.4% of Asian Patients with Lung Adenocarcinoma, Associated with Young Age at Diagnosis

The gist: Oncologists can sometimes look for certain genetic mutations in a patient’s tumor to help determine the best treatment options for that patient. Researchers have recently found that a particular mutation called ROS1 fusion is present in a subgroup of patients consisting of young East Asian patients with lung adenocarcinoma. People with ROS1 mutations in their lung tumors might benefit from treatment with a drug called crizotinib. The drug has not yet been approved for widespread use by the U.S. Food and Drug Administration (FDA), but patients can enroll in clinical trials to gain access to it.

“ROS1 fusion genes were successfully detected independent of gender or smoking history in young East Asian patients with lung adenocarcinoma, a histological subgroup in non-small cell lung cancer (NSCLC), using multiplex reverse transcriptase-polymerase chain reaction (RT-PCR) and immunohistochemistry (IHC) diagnostic tests.

“In NSCLC treatment algorithms, a personalized therapy approach is now being taken based on the genetic characteristics of the cancer. Patients with specific oncogenic molecular aberrations, for example EGFR mutations and ALK gene fusions, respond well to drugs that target these molecular abnormalities. ROS1 is another potential oncogenic molecular driver and this target is sensitive to crizotinib, a drug approved for the treatment of ALK gene fusion NSCLC .

“Researchers from the National Taiwan University Hospital examined 160 surgical specimens from early-stage and 332 specimens of fluid around the lungs (malignant pleural effusions) from late-stage lung adenocarcinoma patients. They initially examined these specimens for EGFR and KRAS mutations as well as ALK gene. Specimens that were negative for these three oncogenic drivers were then examined for ROS1 fusions using RT-PCR and IHC. Fluorescence in situ hybridization (FISH) was used if there was a discrepancy between RT-PCR and IHC.”

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…

ASCO: Zykadia Works Before or After Targeted Lung Ca Tx

Ceritinib (Zykadia) produced good response in non-small cell lung cancer (NSCLC) overexpressing ALK, regardless of prior treatment for that target, an early phase trial showed.

Ceritinib was associated with an overall response rate of 55% in patients previously treated with crizotinib (Xalkori) and 66% in those naive to that ALK inhibitor, Dong-Wan Kim, MD, of the Seoul National University Hospital, and colleagues found.

Editor’s note: This article is about a drug called ceritinib (brand name Zykadia), which was recently approved by the U.S. Food and Dug Administration (FDA), allowing doctors in the U.S. to prescribe it to patients who 1) have advanced non-small cell lung cancer (NSCLC), 2) have tumor cells with mutations in the ALK gene, as detected by molecular testing, and 3) have tried treatment with crizotinib (Xalkori) but experienced worsening of their cancer. According to the new research described in this article, ceritinib may actually be beneficial whether or not the patient was previously treated with crizotinib.

ARIAD Presents Updated Phase 1/2 Data on AP26113 in Patients with ALK+ Non-Small Cell Lung Cancer

“ARIAD Pharmaceuticals, Inc. today announced updated clinical results on its investigational tyrosine kinase inhibitor (TKI), AP26113, in patients with advanced non-small cell lung cancer (NSCLC) from an ongoing Phase 1/2 trial. These study results show anti-tumor activity of AP26113 in patients with crizotinib-resistant anaplastic lymphoma kinase (ALK) positive NSCLC, including patients with brain metastases. Crizotinib is approved for ALK-positive NSCLC patients.”

Editor’s note: This story is about a targeted drug called AP26113, which may benefit some patients with advanced non-small cell lung cancer (NSCLC). Specifically, it has shown promise for patients whose tumors have mutations in the ALK gene, as detected by molecular testing, and who have already been treated with the drug crizotinib (Xalkori) but have grown resistant to it.

Responses with Crizotinib in MET-Amplified Lung Cancer Show New Targetable Form of Disease

In 2011, the drug crizotinib earned accelerated approval by the US FDA to target the subset of advanced non-small cell lung cancers caused by rearrangements of the anaplastic lymphoma kinase (ALK) gene, and subsequently was granted regular approval in 2013. The drug also has shown dramatic responses in patients whose lung cancers harbored a different molecular abnormality, namely ROS1 gene rearrangements. Previously unreported phase 1 clinical trial results now show that crizotinib may have a third important molecular target. In advanced non-small cell lung cancer patients with intermediate and high amplifications of the MET gene, crizotinib produced either disease stabilization or tumor response. Sixty-seven percent of patients with high MET amplification showed prolonged response to the drug, which lasted from approximately 6 months to nearly 2.5 years.”

Editor’s note: Crizotinib (aka Xalkori) is a targeted therapy drug that kills cancer cells by targeting certain molecules found in the cells. It was already known that crizotinib works well for some patients with advanced non-small cell lung cancer (NSCLC) whose cancer cells have mutations in the ALK gene and in the ROS1 gene; such mutations, or “molecular biomarkers,” are detected by a medical procedure known as “molecular testing,” or “genetic testing.” Now, scientists say that crizotinib may also be effective for patients with advanced NSCLC whose tumors have abnormally high activity of a protein called MET, which can also be detected via molecular testing.

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…

FDA Approves Ceritinib (Zykadia) for Metastatic Lung Cancer

“Earlier today the US Food and Drug Administration granted accelerated approval to ceritinib (Zykadia) for the treatment of patients with metastatic ALK-positive non–small-cell lung cancer (NSCLC). About 2% to 7% percent of NSCLC patients have ALK-positive disease.

“The new drug, a tyrosine kinase inhibitor, was approved 4 months early under the FDA’s accelerated approval program and is intended for the treatment of patients who previously received the ALK-inhibitor crizotinib.”

Editor’s note: FDA approval means that doctors can now begin prescribing ceritinib to treat patients with advanced non-small cell lung cancer (NSCLC) whose tumors have mutations in the ALK gene, as detected by molecular testing. We previously posted about ceritinib here.

New Drug Successfully Treats Crizotinib-Resistant, ALK-Positive Lung Cancer

“Although the targeted cancer treatment drug crizotinib is very effective in causing rapid regression of a particular form of lung cancer, patients’ tumors inevitably become resistant to the drug. Now a new drug called ceritinib appears to be effective against advanced ALK-positive non-small cell lung cancer (NSCLC), both in tumors that have become resistant to crizotinib and in those never treated with the older drug. The results of a phase 1 clinical trial conducted at centers in 11 countries are reported in the March 27 New England Journal of Medicine.”

Editor’s note: Crizotinib and ceritinib are meant to treat patients whose tumors have mutations in the ALK gene, as detected by molecular testing.

Phase III Study: Crizotinib Prolongs Progression-Free Survival in Previously Untreated ALK-Positive Advanced NSCLC

“In the phase III PROFILE 1014 study, the anaplastic lymphoma kinase (ALK) inhibitor crizotinib (Xalkori) was found to significantly prolong progression-free survival in previously untreated patients with ALK-positive advanced nonsquamous non–small cell lung cancer (NSCLC) compared with standard platinum-based chemotherapy.

“No unexpected safety issues were identified in the current study, and adverse events were consistent with the known safety profile for crizotinib. Efficacy and safety data from this study will be submitted for presentation at a future medical meeting.”

Editor’s note: Xalkori is a targeted therapy that is meant to treat patients whose tumors have mutations in the ALK gene, as detected by molecular testing.