ALCHEMIST Aims to Curtail Return of Early-Stage Lung Cancer


A series of three new clinical trials (research studies with volunteer patients) is big news for some people affected by early-stage lung cancer. The trials focus on two drugs typically used to treat late-stage adenocarcinoma. These two drugs, Tarceva and Xalkori, may also help stage I, II, and IIIA patients prevent relapse (return of cancer) after their tumors have been surgically removed. The new clinical trials will put the treatments to the test. Continue reading…


Docetaxel Plus Ramucirumab Improves Outcomes in Advanced NSCLC

“The addition of ramucirumab to docetaxel improved outcomes over placebo with docetaxel as a second-line treatment of patients with advanced non-small-cell lung cancer (NSCLC), according to results of the REVEL trial presented at the 2014 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago.

“ ‘Despite advancements in genomics and identification of predictive biomarkers such as EGFR mutations or ALK rearrangement, there is still no… targeted therapy for the majority of patients with squamous and non-squamous carcinoma,’ said Maurice Pérol, MD, of the Cancer Research Center of Lyon in France. Ramucirumab specifically targets VEGFR-2 and inhibits angiogenesis, and it has been shown to improve outcomes in gastric cancer as monotherapy.”

Editor’s note: This article describes a treatment for advanced non-small cell lung cancer (NSCLC) that combines a new targeted drug called ramucirumab with the standard chemotherapy drug docetaxel. In a clinical trial to test the treatment in volunteer patients who had already received one previous treatment, it was found that ramucirumab plus docetaxel provided better patient outcomes than docetaxel plus a placebo.


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.


Novel Assay Developed for Detecting ALK Rearragement in NSCLC

“Researchers have developed a novel technique for detecting ALK rearrangements in non-small cell lung cancers (NSCLCs) that is more sensitive and easier to perform than currently available techniques. The technique can help enhance the routine practice of diagnostic ALK testing on NSCLCs, which is crucial for identifying patients with advanced NSCLC who are most likely to benefit from targeted therapy with an ALK inhibitor.”

Editor’s Note: “Molecular tests” like the one mentioned here can be very important for patients to choose the best treatment plan. Learn more at our Lung Cancer Basics.


A Genomics-Based Classification of Human Lung Tumors

We characterized genome alterations in 1255 clinically annotated lung tumors of all histological subgroups to identify genetically defined and clinically relevant subtypes. More than 55% of all cases had at least one oncogenic genome alteration potentially amenable to specific therapeutic intervention, including several personalized treatment approaches that are already in clinical evaluation.


Circulating Tumor Cells with ALK Rearrangement in ALK-positive NSCLC

ALK rearrangement can be detected in circulating tumor cells of patients with ALK-positive NSCLC by using a filtration technique and filter-adapted fluorescence in situ hybridization, enabling both diagnostic testing and monitoring of crizotinib treatment. Circulating tumor cells harboring a unique ALK rearrangement and mesenchymal phenotype may arise from clonal selection of tumor cells that have acquired the potential to drive metastatic progression of ALK-positive NSCLC.


ALK Rearrangements are Mutually Exclusive with Mutations in EGFR or KRAS: An Analysis of 1683 Patients with Non-Small Cell Lung Cancer

Anaplastic lymphoma kinase (ALK) gene rearrangements define a distinct molecular subset of non-small cell lung cancer (NSCLC). Recently, several case reports and small series have reported that ALK rearrangements can overlap with other oncogenic drivers in NSCLC in crizotinib-naïve and resistant cancers. Our study here shows that functional ALK rearrangements were mutually exclusive with EGFR and KRAS mutations in a large Western patient population. This lack of overlap was also observed in ALK-positive cancers with acquired resistance to crizotinib.


Detection of Circulating Tumor Cells Harboring a Unique ALK Rearrangement in ALK-Positive Non–Small-Cell Lung Cancer

“ALK rearrangement can be detected in CTCs of patients with ALK-positive NSCLC by using a filtration technique and FA-FISH, enabling both diagnostic testing and monitoring of crizotinib treatment. Our results suggest that CTCs harboring a unique ALK rearrangement and mesenchymal phenotype may arise from clonal selection of tumor cells that have acquired the potential to drive metastatic progression of ALK-positive NSCLC…”