Best of ASCO 2013: VeriStrat Assay May Help Select NSCLC Patients for Second-Line Therapy
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.
Second-line therapy for patients with advanced NSCLC after progression on platinum-based regimens typically employs chemotherapy or erlotinib (Tarceva). Improved progression-free survival in patients treated with erlotinib is associated with EGFR-sensitizing mutations, but there are few means of optimizing treatment in patients with wild-type or unknown EGFR mutation status or squamous histology, she noted.
VeriStrat is a commercially available serum-based protein test designed to identify which patients are likely to benefit from an oral EGFR tyrosine kinase inhibitor such as erlotinib or gefitinib (Iressa). The test evaluates pretreatment serum using matrix-assisted laser desorption ionization mass spectrometry to classify a patient as having a “good” or “poor” profile for treatment benefit. In retrospective studies, VeriStrat has demonstrated prognostic and predictive utility.
At the Best of ASCO meeting, Dr. Wakelee presented the results of the current PROSE study, which she said is the first completed prospective biomarker-stratified validation study in oncology to test the treatment/biomarker interaction.
Details of PROSE
The study included 285 patients stratified by ECOG performance status, smoking, and blinded pretreatment VeriStrat classification (VeriStrat “good” or VeriStrat “poor”). Patients were randomly assigned to receive erlotinib or chemotherapy at standard doses. The primary endpoint was overall survival, and the primary hypothesis was that there would be a significant interaction between test status and treatment.
In the per-protocol primary analysis, 68% of the chemotherapy arm and 72% of the erlotinib arm were classified as VeriStrat “good,” while 32% and 28%, respectively, were classified “poor.” EGFR and KRAS analysis was performed in about two-thirds of patients.
VeriStrat Profile Predicted Treatment Outcome
The trial reached its primary objective of significant interaction between treatment and VeriStrat classification, with an interaction P value of .037. Patients in the VeriStrat “poor” group performed worse on erlotinib than on chemotherapy (hazard ratio [HR] = 1.72, 95% confidence interval [CI]: 1.08–2.74) but for the VeriStrat “good” group, treatment assignment made no significant difference in overall survival (HR = 1.09, 95% CI = 0.79–1.50).
Median overall survival by treatment arm was 9.0 months with chemotherapy and 7.7 with erlotinib (a nonsignificant difference). At progression, about half the patients received a third-line regimen.
Differences did emerge, however, according to pretreatment VeriStrat results. Median overall survival was about 11 months for all patients with the VeriStrat “good” profile, whether they received erlotinib or chemotherapy, but for VeriStrat “poor” patients, overall survival was doubled with chemotherapy, 6.4 months vs 3 months with erlotinib, Dr. Wakelee reported.
The results suggested that VeriStrat status is predictive of a differential overall survival benefit for erlotinib vs chemotherapy in the second-line setting, the authors maintained.
Clinically Useful Treatment Guide
Describing the findings at the Best of ASCO meeting, Dr. Wakelee concluded, “The results of PROSE indicate that the 30% to 35% of patients classified as VeriStrat ‘poor’ have better survival with chemotherapy than with erlotinib, but they have a worse prognosis than the ‘good’ group. The 65% to 70% classified as VeriStrat ‘good’ have similar survival with erlotinib or chemotherapy, and better prognosis than the ‘poor’ group.”
“Serum proteomic VeriStrat classification may be clinically useful in guiding treatment decisions in NSCLC patients with unknown or wild-type EGFR status in the second-line setting,” she commented.
“For those who questioned the utility of erlotinib as a second-line option for EGFR wild-type NSCLC, this may be helpful,” she added, “However, we await the response rate and progression-free survival data to fully evaluate the results of this study.”
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
