Shirish Gadgeel1, Glenwood Goss2, Jean-Charles Soria3, Enriqueta Felip4, Vassilis Georgoulias5, Shun Lu6, Manuel Cobo7, Konstantinos Syrigos8, Ki Hyeong Lee9, Erdem Göker10, Salih Z Guclu11, Dolores Isla12, Alessandro Morabito13, Nicholas Dupuis14, Claudia Bühnemann15, Nicole Krämer16, Flavio Solca17, Eva Ehrnrooth18, Andrea Ardizzoni19. 1. Karmanos Cancer Institute/Wayne State University, 4100 John R, Detroit, MI 48201, USA. Electronic address: gadgeels@karmanos.org. 2. The Ottawa Hospital Research Institute and University of Ottawa, 501 Smyth Rd, Ottawa, Ontario K1H 8L6, Canada. Electronic address: ggoss@toh.ca. 3. Gustave Roussy Cancer Campus and University Paris-Sud, 114 Rue Edouard Vaillant, 94800 Villejuif, Paris, France. Electronic address: jean-charles.soria@gustaveroussy.fr. 4. Vall d'Hebron University Hospital, Passeig Vall d'Hebron, Barcelona, 08035, Spain. Electronic address: efelip@vhebron.net. 5. University Hospital of Heraklion, Iraklio 711 10, Heraklion, Crete, Greece. Electronic address: georgouliasv@gmail.com. 6. Shanghai Chest Hospital, China(1). Electronic address: shun_lu@hotmail.com. 7. Hospital Universitario Málaga Regional y Virgen de la Victoria, IBIMA, 29010 Malaga, Spain. Electronic address: manuelcobodols@yahoo.es. 8. Athens School of Medicine, National & Kapodistrian University, Athens 11527, Greece. Electronic address: ksyrigos@med.uoa.gr. 9. Chungbuk National University College of Medicine, 410 Seongbong-ro, Cheongju 361-711, South Korea. Electronic address: kihlee@chungbuk.ac.kr. 10. Ege University Faculty of Medicine, 35040 Bornova, Izmir, Turkey. Electronic address: erdem.goker@gmail.com. 11. Izmir Chest Diseases Research Hospital, Dr. Suat Seren Göğüs Hastalıkları ve Cerrahisi Eğitim ve Araştırma Hastanesi, Gaziler Caddesi No:331 P1 Blok 2.kat, Konak, Izmir, Turkey. Electronic address: szguclu@yahoo.com. 12. University Hospital Lozano Blesa, Avenida San Juan Bosco, 15, 50009 Zaragoza, Spain. Electronic address: lola.isla@gmail.com. 13. Istituto Nazionale Tumori "Fondazione G. Pascale", IRCCS, Via Mariano Semmola, 80131 Naples, Italy. Electronic address: alessandromorabito1@virgilio.it. 14. Biodesix Inc., 2970 Wilderness Pl, Boulder, CO 80301, USA. Electronic address: nicholas.dupuis@biodesix.com. 15. Boehringer Ingelheim Pharma GmbH & Co. KG, Birkendorfer Str. 65, 88400 Biberach, Germany. Electronic address: claudia.buehnemann@boehringer-ingelheim.com. 16. Staburo GmbH, Aschauer Str. 30, 81549 Munich, Germany(2). Electronic address: nicole.kraemer.ext@boehringer-ingelheim.com. 17. Boehringer Ingelheim RCV GmbH & Co KG, Doktor-Boehringer-Gasse 5-11, 1120 Vienna, Austria. Electronic address: flavio.solca@boehringer-ingelheim.com. 18. Boehringer Ingelheim, Danmark A/S, Stroedanvej 52, Copenhagen 2100, Denmark. Electronic address: eva.ehrnrooth@boehringer-ingelheim.com. 19. University Hospital, Via Albertoni 15, 40138 Bologna, Italy. Electronic address: andrea.ardizzoni@aosp.bo.it.
Abstract
OBJECTIVES: Identification of biomarkers associated with clinical benefit may be crucial in establishing optimal treatment choice for patients with squamous cell carcinoma (SCC) of the lung after first-line chemotherapy. In this study, the ability of the VeriStrat serum protein test to predict differential clinical benefit with afatinib versus erlotinib, and the association of VeriStrat status with clinical outcomes irrespective of EGFR-TKI used, was assessed in a retrospective analysis of the phase III LUX-Lung 8 trial. MATERIALS AND METHODS: Pretreatment plasma samples were analyzed using matrix-assisted laser desorption ionization time-of-flight mass spectrometry. Spectra were evaluated to assign a VeriStrat 'Good' (VS-G) or VeriStrat 'Poor' (VS-P) classification. Overall survival (OS), progression-free survival, and other endpoints were assessed with respect to pretreatment VeriStrat status; OS was the primary efficacy variable. Outcomes with other efficacy endpoints were similar. RESULTS: Of 795 patients randomized in LUX-Lung 8, 675 were classified (VS-G: 412; VS-P: 263). In the VS-G group, OS was significantly longer with afatinib versus erlotinib (HR 0.79 [95% CI: 0.63-0.98]). In the VS-P group, there was no significant difference in OS between afatinib and erlotinib (HR 0.90 [0.70-1.16]). However, there was no interaction between VeriStrat classification and treatment group for OS (pinteraction=0.5303). OS was significantly longer in VS-G versus VS-P patients, both in the overall VeriStrat-classified population (HR 0.41 [0.35-0.49]) and afatinib-treated patients (HR 0.40 [0.31-0.51]). Multivariate analysis showed that VeriStrat was an independent predictor of OS in afatinib-treated patients, regardless of ECOG PS or best response to first-line chemotherapy. CONCLUSION: VS-G classification is strongly associated with favorable survival outcomes with either afatinib or erlotinib compared with VS-P classification. In VS-G patients, survival outcomes with afatinib are superior to those with erlotinib. VeriStrat classification may guide treatment decisions in patients with SCC of the lung. ClinicalTrials.gov registration number: NCT01523587.
RCT Entities:
OBJECTIVES: Identification of biomarkers associated with clinical benefit may be crucial in establishing optimal treatment choice for patients with squamous cell carcinoma (SCC) of the lung after first-line chemotherapy. In this study, the ability of the VeriStrat serum protein test to predict differential clinical benefit with afatinib versus erlotinib, and the association of VeriStrat status with clinical outcomes irrespective of EGFR-TKI used, was assessed in a retrospective analysis of the phase III LUX-Lung 8 trial. MATERIALS AND METHODS: Pretreatment plasma samples were analyzed using matrix-assisted laser desorption ionization time-of-flight mass spectrometry. Spectra were evaluated to assign a VeriStrat 'Good' (VS-G) or VeriStrat 'Poor' (VS-P) classification. Overall survival (OS), progression-free survival, and other endpoints were assessed with respect to pretreatment VeriStrat status; OS was the primary efficacy variable. Outcomes with other efficacy endpoints were similar. RESULTS: Of 795 patients randomized in LUX-Lung 8, 675 were classified (VS-G: 412; VS-P: 263). In the VS-G group, OS was significantly longer with afatinib versus erlotinib (HR 0.79 [95% CI: 0.63-0.98]). In the VS-P group, there was no significant difference in OS between afatinib and erlotinib (HR 0.90 [0.70-1.16]). However, there was no interaction between VeriStrat classification and treatment group for OS (pinteraction=0.5303). OS was significantly longer in VS-G versus VS-P patients, both in the overall VeriStrat-classified population (HR 0.41 [0.35-0.49]) and afatinib-treated patients (HR 0.40 [0.31-0.51]). Multivariate analysis showed that VeriStrat was an independent predictor of OS in afatinib-treated patients, regardless of ECOG PS or best response to first-line chemotherapy. CONCLUSION: VS-G classification is strongly associated with favorable survival outcomes with either afatinib or erlotinib compared with VS-P classification. In VS-G patients, survival outcomes with afatinib are superior to those with erlotinib. VeriStrat classification may guide treatment decisions in patients with SCC of the lung. ClinicalTrials.gov registration number: NCT01523587.