A Subset of EGFR Mutations in Lung Cancer Is Associated with Resistance to TKI Treatment

Non-small cell lung cancers (NSCLC) with a mutation in the EGFR gene can usually be treated with EGFR-tyrosine kinase inhibitors (TKIs) such as erlotinib (Tarceva), gefitinib (Iressa), afatinib, neratinib, or dacomitinib. However, mutations that are located in a region of the EGFR gene called exon 20 are associated with a lack of response to TKI treatment. A study of tumor tissue from adenocarcinoma (a type of NSCLC) found that such exon 20 mutations are present in approximately 10% of EGFR-mutant adenocarcinoma and 3% of all adenocarcinoma, that they are more common in NSCLC patients who never smoked, and that there are a wide variety of different exon 20 mutations, some of which may be more responsive to TKI treatment than others.

TKIs Are Effective First-Line Treatment in EGFR-Mutant Advanced NSCLC

Four phase III studies compared the tyrosine kinase inhibitors (TKIs) erlotinib (Tarceva) or gefitinib (Iressa) to standard chemotherapy as first-line treatment for EGFR-mutant advanced non-small cell lung cancer (NSCLC). TKI treatment increased progression-free survival (ie, the length of time without the cancer worsening), but did not improve overall survival compared to chemotherapy. In one study, TKI-treated patients maintained a higher quality of life for longer than chemotherapy-treated patients. The findings suggest that TKI treatment should become the standard first-line treatment in advanced NSCLC with mutations in the EGFR gene.

Research paper: http://link.springer.com/article/10.1007/s11523-013-0258-9/fulltext.html

Sugar Absorption Measurement May Predict Survival After Radiation Therapy for Stage I NSCLC

A measurement called SUVmax may predict progression-free survival after radiation therapy in stage I non-small cell lung cancer (NSCLC). SUVmax uses a positron-emission tomography (PET)/computed tomography (CT) scan to measure the maximum amount of sugar absorbed by cells in suspicious lesions. Cells that absorb more sugar are more likely to be cancerous. In a new study, 95 patients with inoperable, previously untreated NSCLC who had undergone SUVmax measurement received treatment with stereotactic body radiation therapy (SBRT). SUVmax measurements predicted overall and progression-free survival. The researchers say that SUVmax measurements could help doctors tailor radiation therapy to specific patients.

Variations in Certain Genes May Predict Clinical Outcomes in Early-Stage Lung Cancer

Early-stage non-small cell lung cancer (NSCLC) is usually treated with surgical removal of the tumor. However, in up to 50% of patients, the cancer will return within 5 years. A study of genetic variations that affect the function of microRNAs (small molecules involved in gene expression) found that several of them, including variations in the FAS, FZD4, SP1, and DROSHA genes, were associated with higher or lower probabilities of cancer recurrence and survival. Tests for such microRNA-related genetic variations may eventually help identify high-risk, early-stage NSCLC patients who would benefit from additional treatment after surgery.

Reolysin Shrinks Lung Cancer Tumors in Clinical Trial

A phase II study of the novel cancer treatment Reolysin in 20 patients with advanced squamous cell carcinoma (SCC) of the lung, a type of non-small cell lung cancer (NSCLC), showed a reduction in tumor size in 95% of patients. Patients were given Reolysin in combination with the chemotherapy drugs carboplatin (Paraplatin) and paclitaxel (Taxol or Abraxane); on average, their tumors shrank by about one-third. This finding suggests that Reolysin may be useful for presurgical treatment of tumors. Reolysin, made by the company Oncolytics, is a form of a virus called reovirus. Most adults have been exposed to reovirus, which usually does not produce symptoms. However, reovirus selectively infects and kills tumor cells.

Press release: http://www.oncolyticsbiotech.com/news_items/details?press_release_id=1921

CollabRx Updates Online Tool for Finding Targeted Therapies for Lung Cancer

CollabRx has released a new version of its Therapy Finder™ application for lung cancer, an online tool that recommends targeted therapies and clinical trials to physicians based on genetic information about a patient’s tumor. Available at: http://therapy.collabrx.com/lung/, the updated application incorporates information about mutations in the ROS1 gene, which can make patients eligible for treatment with a class of drugs called ALK inhibitors, including crizotinib (Xalkori). The new tool also includes updated information about selumetinib, an investigational drug that may benefit patients whose tumors carry a mutation in the KRAS gene.

CHFR Protein Levels Predict Effectiveness of Chemotherapy

A study of patients with advanced non-small cell lung cancer (NSCLC) given chemotherapy with carboplatin (Paraplatin) and paclitaxel (Taxol or Abraxane) found that patients with lower levels of the protein CHFR were more likely to respond to the treatment and survived longer than patients with high CHFR levels. These findings suggest that CHFR levels could be a useful biomarker for indicating patients likely to respond to so-called taxane chemotherapy drugs like Taxol, Abraxane, or docetaxel (Taxotere). In the future, treatments that target CHFR may be developed to increase responsiveness to taxane chemotherapy in patients with high CHFR levels.

FDA Grants Priority Review for EGFR-Mutant Lung Cancer Drug Afatinib

A promising new drug for a subtype of non-small cell lung cancer (NSCLC) was recently granted priority review status by the U.S. Food and Drug Administration (FDA). If approved, afatinib would be the first drug on the market specifically for treating advanced or metastatic NSCLC associated with epidermal growth factor receptor (EGFR) mutations. Continue reading…