“Combined results from subset analyses of the TIGER-X and TIGER-2 clinical trials show that the VeriStrat test stratifies T790M-mutated patients with previously-treated, advanced non-small cell lung cancer (NSCLC) who are more or less likely to experience longer progression-free survival (PFS) when treated with a third-generation EGFR-TKI therapy. Clinical trial data suggesting the test’s potential for identifying better candidates for third-generation EGFR-TKI therapy were presented in Chicago last Friday at the at the IASLC Multidisciplinary Symposium in Thoracic Oncology hosted by the International Association for the Study of Lung Cancer.”
“In a Japanese phase III trial (DELTA) reported in the Journal of Clinical Oncology, Kawaguchi et al found that erlotinib (Tarceva) was associated with no progression-free survival or overall survival advantage as second- or third-line therapy in EGFR-unselected patients with non–small cell lung cancer.
“In this open-label trial, 301 patients with stage IIIB or IV NSCLC, previous treatment with one or two chemotherapy regimens, evaluable or measurable disease, and Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2 were randomly assigned between August 2009 and July 2012 to erlotinib at 150 mg daily (n = 150) or docetaxel at 60 mg/m2every 3 weeks (n = 151). The primary endpoint was progression-free survival. In total, 109 patients (73%) in the erlotinib group and 90 (60%) in the docetaxel group had EGFR wild-type disease. Study treatment was third line in 19% and 14%, respectively.”
Editor’s note: This clinical trial tested a drug called erlotinib (brand name Tarceva), which is already known to be an effective treatment for lung cancer patients whose tumors have mutations in the EGFR gene. However, in this trial, the scientists were interested in whether erlotinib might help all patients, regardless of whether EGFR is mutated. The results show that erlotinib is no more effective than chemo for patients without EGFR mutations. But we recently posted another story about a protein test that may predict whether a patient without EGFR mutations might benefit from erlotinib treatment.
“There are conflicting data on whether epidermal growth factor receptor (EGFR) inhibitor therapy is beneficial in second-line treatment of lung cancer patients with unknown or wild-type EGFR status. In a phase III trial (PROSE) reported in The Lancet Oncology, Gregorc et al assessed the predictive value of a proteomic signature serum protein test for likely outcome of EGFR inhibitor therapy in non–small cell lung cancer (NSCLC) patients receiving second-line therapy with the EGFR inhibitor erlotinib (Tarceva) vs chemotherapy. They found that the test was predictive of differential survival benefit for erlotinib vs chemotherapy, with patients classified by the test as likely to have poor outcome on EGFR inhibitor therapy having better outcome on chemotherapy.”
“Overall survival was significantly better with chemotherapy among patients with a proteomic classification of poor, whereas there was no difference between chemotherapy and erlotinib in patients with a classification of good.”
EGFR inhibitors like erlotinib (Tarceva) can greatly benefit non-small cell lung cancer (NSCLC) patients with mutations in the EGFR gene, but their effectiveness in patients without such mutations is less clear. VeriStrat is a blood test meant to predict how well patients would respond to EGFR-inhibitor treatment. A study designed to evaluate VeriStrat examined patients with advanced NSCLC without EGFR mutations in whom platinum-based chemotherapy had stopped working and who received either different chemotherapy or Tarceva as their second-line treatment. Patients with a VeriStrat result of ‘poor’ survived longer when treated with chemotherapy than with Tarceva. In contrast, chemotherapy and Tarceva worked equally well for those with a ‘good’ test result. Good VeriStrat results also predicted longer survival in general.
“VeriStrat, a serum-based protein assay, can help select which patients with non–small cell lung cancer (NSCLC) who are not known to have epidermal growth factor receptor (EGFR) mutations might benefit from an EGFR-targeted agent, according to a study described at the 2013 Best of ASCO Los Angeles meeting by Heather A. Wakelee, MD, Associate Professor of Medicine, Stanford University, Palo Alto, California.”
Colorado’s Medicare provider has announced that it will cover VeriStrat, a test designed to guide decisions about second-line therapies for advanced non-small cell lung cancer (NSCLC). The main second-line therapy options in NSCLC include chemotherapy or the drug erlotinib (Tarceva). While Tarceva can significantly improve outcomes in patients with mutations in the EGFR gene, it also benefits some patients without these mutations. VeriStrat, a rapid blood test, helps predict which of these patients would be more likely to respond to Tarceva and which would be better served by other treatments. Medicare coverage will allow many more patients in Colorado to access this useful tool.
Augustin A, Lamerz J ... Essioux L, Klughammer B, Mol Cancer Ther, Jan 31, 2013
Although both erlotinib and gefitinib target the epidermal growth factor receptor (EGFR), erlotinib is effective in patients with EGFR wild-type or mutated tumors, whereas gefitinib is only beneficial for patients with activating mutations. To determine whether these differences in clinical outcomes can be attributed to their respective protein interaction profiles, a label-free, quantitative chemical proteomics study was performed. We propose that, in an EGFR wild-type context, erlotinib may have a complementary mode of action by inhibiting integrin-linked kinase (ILK), -parvin and PINCH (IPP) complex activities, resulting in the slowing down of the metastatic process of epithelial tumors.
Stinchcombe TE, Roder J ... Moore DT, Socinski MA, J Thorac Oncol, Jan 30, 2013
In a multicenter randomized phase II trial of gemcitabine (arm A), erlotinib (arm B), and gemcitabine and erlotinib (arm C), similar progression-free survival (PFS) and overall survival (OS) were observed in all arms. We performed an exploratory, blinded, retrospective analysis of plasma or serum samples collected as part of the trial to investigate the ability of VeriStrat (VS) to predict treatment outcomes.
Gemcitabine is the superior treatment for elderly patients with VS Poor status. First-line erlotinib for elderly patients with VS Good status may warrant further investigation.
Annals of Cancer Research and Therapy | Sep 28, 2012
Bevacizumab (Avastin), which is approved for treatment of a number of advanced-stage cancer types, is commonly avoided in patients with brain metastases (cancer that has spread to the brain) because of fear of brain hemorrhages (bleeding in the brain). A retrospective study of 52 patients with advanced non-small cell lung cancer (NSCLC) who had received chemotherapy containing Avastin found no cases of serious bleeding events and no significant differences in survival or treatment side effects between patients with or without brain metastases. Avastin may therefore be a safe treatment option in NSCLC with brain metastases.
Research paper: https://www.jstage.jst.go.jp/article/acrt/20/2/20_47/_pdf