Randomized proteomic stratified phase III study of second-line erlotinib (E) versus chemotherapy (CT) in patients with inoperable non-small cell lung cancer (PROSE).

Lung Cancer - Non-Small Cell Metastatic
Session Type and Session Title: 
Oral Abstract Session, Lung Cancer - Non-small Cell Metastatic
Abstract Number: 
J Clin Oncol 31, 2013 (suppl; abstr LBA8005)
Chiara Lazzari, Silvia Novello, Sandro Barni, Michele Aieta, Filippo De Marinis, Tommaso De Pas, Francesco Grossi, Manlio Mencoboni, Alessandra Bearz, Irene Floriani, Valter Torri, Alessandra Bulotta, Julia Grigorieva, Joanna Roder, Claudio Doglioni, Heinrich Roder, Luisella Righi, Silvia Foti, Angela Bachi, Vanesa Gregorc; Department of Oncology, Istituto Scientifico Ospedale San Raffaele, Milan, Italy; University of Turin, Orbassano, Italy; Department of Medical Oncology, Treviglio and Caravaggio Hospital, Treviglio, Italy; Centro Di Riferimento Oncologico DI Basilicata, Rionero in Vulture, Italy; San Camillo-Forlanini Hospital, Rome, Italy; Division of Thoracic Oncology, European Institute of Oncology, Milan, Italy; Lung Cancer Unit, National Institute for Cancer Research, Genova, Italy; Ospedale Villa Scassi, Genova, Italy; IRCCS Centro Rif Oncologico, Pordenone, Italy; Laboratory of Clinical Trials, Oncology Department, Istituto di Ricerche Farmacologiche, Milano, Italy; Oncology Department, Mario Negri Institute, Milan, Italy; Biodesix Inc., Boulder, CO; Biodesix Inc., Broomfield, CO; Department of Pathology, Istituto Scientifico Ospedale San Raffaele, Milan, Italy; Department of Clinical and Biological Sciences-Pathology, San Luigi Hospital, Orbassano, Italy; Laboratory of Proteomics, Istituto Scientifico Ospedale San Raffaele, Milan, Italy

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Abstract Disclosures


Background: Second-line therapy for advanced NSCLC patients (pts) after progression on platinum-based regimens typically employs CT or E. Improved PFS in E-treated pts is associated with EGFR sensitizing mutations. However, a test for optimizing treatment in pts with wild-type or unknown EGFR mutation status or squamous histology is of clinical value. VeriStrat (VS) is a serum protein test that assigns "good" (VSG) or "poor" (VSP) classification and has demonstrated prognostic and predictive utility. PROSE is a multicenter prospective randomized biomarker validation trial, designed to evaluate the ability of VS to predict survival in second-line NSCLC pts treated with E or CT. It is the first completed prospective randomized biomarker validation trial following the MARVEL design (Freidlin et al. JNCI. 2010). Methods: 285 pts, stratified by ECOG-PS, smoking, and blinded pretreatment VS classification, were randomized 1:1 to receive E or CT at standard doses. Primary endpoint was overall survival (OS) and the primary hypothesis was significant interaction between VS status and treatment. Sample size was calculated based on an estimated 65%/35% VSG:VSP ratio and hazard ratio (HR) for interaction of 2.35, with a 2-sided α=0.05 and 90% power. Results: 285 pts were randomized and 263 (129 CT, 134 E) included in the per protocol primary analysis. 68% of pts in CT arm and 72% in E arm were classified as VSG. Analysis was performed at 226 events. The trial reached its primary objective of significant interaction between treatment and VeriStrat classification with an interaction p value of 0.037. Pts in the VSP group performed worse on E compared to CT (HR: 1.72, 95% CI: 1.08-2.74); there was no significant difference in OS between treatments in the VSG group (HR: 1.09, 95% CI:0.79-1.50). 194/198 pts with histologic diagnosis had tissue available for EGFR and KRAS mutations. Conclusions: The results suggest that VS status is predictive of differential OS benefit for E versus CT in second line setting, complementing the result from a retrospective analysis of NCIC BR.21 where the prognostic behavior of VS was established (Carbone et al. JTO. 2012). Clinical trial information: NCT00989690.