An established multivariate serum protein test can be used to classify patients according to whether they are likely to have a good or poor outcome after treatment with EGFR tyrosine-kinase inhibitors.
Researchers have assessed the predictive power of this test in the comparison of Erlotinib ( Tarceva ) and chemotherapy in patients with non-small-cell lung cancer.
From Feb 26, 2008, to April 11, 2012, patients ( aged greater than or equal to 18 years ) with histologically or cytologically confirmed, second-line, stage IIIB or IV non-small-cell lung cancer were enrolled in 14 centres in Italy.
Patients were stratified according to a minimisation algorithm by Eastern Cooperative Oncology Group performance status, smoking history, centre, and masked pretreatment serum protein test classification, and randomly assigned centrally in a 1:1 ratio to receive Erlotinib ( 150 mg/day, orally ) or chemotherapy ( Pemetrexed [ Alimta ] 500 mg/m2, intravenously, every 21 days, or Docetaxel [ Taxotere ] 75 mg/m2, intravenously, every 21 days ).
The proteomic test classification was masked for patients and investigators who gave treatments, and treatment allocation was masked for investigators who generated the proteomic classification.
The primary endpoint was overall survival and the primary hypothesis was the existence of a significant interaction between the serum protein test classification and treatment.
Analyses were done on the per-protocol population.
142 patients were randomly assigned to chemotherapy and 143 to Erlotinib, and 129 ( 91% ) and 134 ( 94% ), respectively, were included in the per-protocol analysis.
88 ( 68% ) patients in the chemotherapy group and 96 ( 72% ) in the erlotinib group had a proteomic test classification of good.
Median overall survival was 9.0 months in the chemotherapy group and 7.7 months in the Erlotinib group.
Researchers have noted a significant interaction between treatment and proteomic classification ( p interaction=0.017 when adjusted for stratification factors; p interaction=0.031 when unadjusted for stratification factors ).
Patients with a proteomic test classification of poor had worse survival on Erlotinib than on chemotherapy ( hazard ratio, HR=1.72; p=0.022 ).
There was no significant difference in overall survival between treatments for patients with a proteomic test classification of good ( adjusted HR 1.06; p=0.714 ).
In the group of patients who received chemotherapy, the most common grade 3 or 4 toxic effect was neutropenia ( 15% vs less than 1% in the Erlotinib group ), whereas skin toxicity ( less than 1% vs 16% ) was the most frequent in the Erlotinib group.
The findings have indicated that serum protein test status is predictive of differential benefit in overall survival for Erlotinib versus chemotherapy in the second-line setting.
Patients classified as likely to have a poor outcome have better outcomes on chemotherapy than on Erlotinib. ( Xagena )
Gregorc V et al, The Lancet Oncology 2014; 15: 713-721