New guidelines recommend lung cancer patients be genetically tested to determine whether they are amenable to a class of drugs called tyrosine kinase inhibitors. Patients with EGFR or ALK mutations could benefit more from such targeted therapies, and suffer fewer side effects, than with chemotherapy. Continue reading…
A patient with advanced lung adenocarcinoma, a type of non-small cell lung cancer (NSCLC), had relapsed from, or failed to respond to, numerous chemotherapy agents and targeted therapies and was deteriorating rapidly. Previous molecular testing had found no mutations in commonly tested biomarker genes, but a follow-up test detected a mutation in the ROS1 gene. The patient then started treatment with crizotinib (Xalkori) and experienced a dramatic improvement, including tumor shrinkage. Xalkori treatment has continued for 12 weeks so far, with no sign of cancer progression. This case demonstrates the remarkable effectiveness that Xalkori can have in ROS1-mutant NSCLC, as well as the need for prompt and comprehensive molecular testing for all NSCLC patients.
MET, also known as c-Met, is a protein that normally occurs only at low levels in healthy tissues, but is overabundant and often mutated in many tumors, including non-small cell lung cancer (NSCLC). It is therefore a promising target for cancer treatments called MET inhibitors. However, currently available MET inhibitors also interfere with other proteins, leading to serious side effects and limiting their usefulness. In a recent study, researchers showed that the new MET inhibitors EMD 1214063 and EMD 1204831 are highly selective for MET only. The two drugs also shrank NSCLC tumors implanted into mice, suggesting that they may be promising treatments for NSCLC.
All patients with advanced adenocarcinoma of the lung, a type of non-small cell lung cancer (NSCLC), should be tested for mutations in the EGFR and ALK genes, according to guidelines developed by three prominent professional medical societies. Mutations in these genes predict a much higher likelihood of benefitting from treatment with EGFR inhibitors like erlotinib (Tarceva) and gefitinib (Iressa) o,r ALK inhibitors like crizotinib (Xalkori), respectively. The tests should be performed for all adenocarcinoma patients as soon as advanced disease is detected, regardless of the sex, race, smoking history, or other clinical risk factors.
Preliminary results from an ongoing phase II clinical trial of new lung cancer drug AXL1717 suggest that the drug effectively treats non-small cell lung cancer (NSCLC). In the study, patients with advanced NSCLC received either AXL1717 or chemotherapy with docetaxel (Taxotere) as a second-line treatment. AXL1717, which works by attacking a protein called IGF1R, appeared to be as effective as Taxotere at delaying cancer progression. AXL1717 may be a treatment option for patients who do not respond or become resistant to Taxotere or other second-line treatments. AXL1717 is manufactured by drug company Axelar. More information about the clinical trial can be found here: http://clinicaltrials.gov/show/NCT01561456
Some patients with non-small cell lung cancer (NSCLC) have tumor mutations called “RET fusions.” RET fusions are especially common in patients who have adenocarcinoma, never smoked, and/or have no mutations in other genes commonly associated with NSCLC. In an ongoing phase II clinical trial, three patients with adenocarcinoma and RET fusions appeared to respond well to the drug cabozantinib (Cometriq). The tumors of two of the patients shrank during Cometriq treatment, while the third experienced stable disease. Further studies are needed, but these results suggest that Cometriq may be an effective treatment for NSCLC patients with RET fusions.
The UK’s National Institute for Health and Clinical Excellence (NICE) has provisionally recommended against the use of National Health Service resources to provide crizotinib (Xalkori) to patients. NICE considers the drug to be too expensive for the expected benefit. Xalkori is used to treat patients with previously treated non-small cell lung cancer (NSCLC) who have mutations in the ALK gene. The drug has been approved in the U.S. since August, 2011, and conditionally approved in Europe since October, 2012. Patients in the UK can still get access to Xalkori, but would have to cover the cost (£4,689/$7,100 for a 30-day supply) themselves. NICE’s provisional guidance is up for comment, after which a second draft guidance will be issued. More details at: http://www.pharmatimes.com/Article/13-03-27/NICE_issues_draft_no_for_Pfizer_s_Xalkori_but_opens_consultation.aspx
Neutropenia (a reduction in white blood cells) is a rare, but potentially serious side effect of the cancer drug gefitinib (Iressa). Iressa is used to treat non-small cell lung cancer (NSCLC) with mutations in the EGFR gene. A patient with EGFR-mutant advanced adenocarcinoma of the lung (a type of NSCLC) was treated with Iressa. Her tumor shrank, but she experienced severe neutropenia, leaving her at risk of dangerous infections. She was switched to erlotinib (Tarceva), another EGFR inhibitor, after which her neutropenia cleared up. The patient has since continued on Tarceva without neutropenia or cancer progression for over 9 months. This case suggests that Iressa-induced neutropenia can be safely treated by switching to Tarceva, although caution should be used in drawing conclusions from a single case study.
Updated results from a clinical trial showed that patients who were treated with the drug erlotinib (Tarceva) had better quality of life than those receiving standard chemotherapy. The OPTIMAL study is a phase III clinical trial investigating erlotinib (Tarceva) as a first-line treatment for people with advanced non-small cell lung cancer (NSCLC) who have a mutation in the EGFR gene. Tarceva-treated patients scored higher on questionnaires assessing physical, social/family, emotional, and functional well-being. The updated results also confirmed that Tarceva-treated patients experienced longer periods without worsening of their cancer compared to chemotherapy-treated patients.