Predictive value of a proteomic signature in patients with non-small-cell lung cancer treated with second-line erlotinib or chemotherapy (PROSE): A biomarker-stratified, randomised phase 3 trial

Vanesa Gregorc, Silvia Novello, Chiara Lazzari, Sandro Barni, Michele Aieta, Manlio Mencoboni, Francesco Grossi, Tommaso De Pas, Filippo De Marinis, Alessandra Bearz, Irene Floriani, Valter Torri, Alessandra Bulotta, Angela Cattaneo, Julia Grigorieva, Maxim Tsypin, Joanna Roder, Claudio Doglioni, Matteo Giaj Levra, Fausto PetrelliSilvia Foti, Mariagrazia Viganò, Angela Bachi, Heinrich Roder

Research output: Contribution to journalArticle

Abstract

Background: 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. We assessed the predictive power of this test in the comparison of erlotinib and chemotherapy in patients with non-small-cell lung cancer. Methods: From Feb 26, 2008, to April 11, 2012, patients (aged ≥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 500 mg/m2, intravenously, every 21 days, or docetaxel 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. This trial is registered with ClinicalTrials.gov, number NCT00989690. Findings: 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 (95% CI 6·8-10·9) in the chemotherapy group and 7·7 months (5·9-10·4) in the erlotinib group. We noted a significant interaction between treatment and proteomic classification (pinteraction=0·017 when adjusted for stratification factors; pinteraction=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 1·72 [95% CI 1·08-2·74], 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 [0·77-1·46], p=0·714). In the group of patients who received chemotherapy, the most common grade 3 or 4 toxic effect was neutropenia (19 [15%] vs one [

Original languageEnglish
Pages (from-to)713-721
Number of pages9
JournalThe Lancet Oncology
Volume15
Issue number7
DOIs
Publication statusPublished - 2014

ASJC Scopus subject areas

  • Oncology

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