1235P - Cilengitide (CIL) combined with cetuximab and platinum-based chemotherapy as first-line treatment in advanced non-small cell lung cancer (NSCLC) pa...

Date 27 September 2014
Event ESMO 2014
Session Poster Display session
Topics Anti-Cancer Agents & Biologic Therapy
Non-Small-Cell Lung Cancer, Metastatic
Presenter Johan Vansteenkiste
Citation Annals of Oncology (2014) 25 (suppl_4): iv426-iv470. 10.1093/annonc/mdu349
Authors J.F. Vansteenkiste1, F. Barlesi2, C. Waller3, J. Bennouna4, C. Gridelli5, E. Goekkurt6, D. Verhoeven7, A. Szczesna8, M. Feurer9, J. Milanowski10, P. Germonpre11, H. Lena12, D. Atanackovic13, M. Krzakowski14, C. Hicking15, J. Straub16, M. Picard17, W. Schuette18, K. O’ Byrne19
  • 1Respiratory Oncology Unit, University Hospital KU Leuven, 3000 - Leuven/BE
  • 2Multidisciplinary Oncology & Therapeutic Innovations, Aix Marseille University; Assistance publique Hôpitaux de Marseille, Marseille/FR
  • 3Hematology, Oncology And Stem Cell Transplantation, University Hospital of Freiburg, Freiburg/DE
  • 4Department D’oncologie Medicale, Centre Rene Gauducheau, Saint-Herblain Cedex/FR
  • 5Medical Oncology, U.O. Oncologia Medica, Azienda Ospedaliera “S.G. Moscati,”, Avellino/IT
  • 6Department Of Oncology And Hematology, Universitaetsklinikum Aachen, Aachen/DE
  • 7Medical Oncology, AZ Klina, Iridium cancer network, Antwerp/BE
  • 8Lung Diseases, Mazowieckie Centrum Leczenia Chorob Pluc i Gruzlicy, Otwock/PL
  • 9Lung Cancer, Lungenpraxis Muenchen, Muenchen/DE
  • 10Department Of Pneumology, Oncology And Allergology, Medical University of Lublin, Lublin/PL
  • 11Pulmonary Medicine, AZ Maria Middelares, Ghent/BE
  • 12Pneumology, CHU Rennes, Rennes Cedex/FR
  • 13Oncology/hematology/stem Cell Transplantation, University Medical Center Hamburg-Eppendorf, Hamburg/DE
  • 14Lung & Thoracic Tumours, The Maria Sklodowska-Curie Memorial Cancer Center & Institute of Oncology, Warsaw/PL
  • 15Global Biostatistics, Merck KGaA, Darmstadt/DE
  • 16Translational Innovation Platform Oncology, Merck Kgaa, Merck KGaA, Darmstadt/DE
  • 17Global Clinical Development Center Oncology, Merck KGaA, Darmstadt/DE
  • 18Klinik Fuer Innere Medizin Ii, Krankenhaus Martha-Maria Halle-Doelau, Halle/DE
  • 19Cancer Services, Princess Alexandra Hospital, Brisbane/AU

Abstract

Aim

CIL is a selective, competitive inhibitor of αvß3 and αvß5 integrins designed to attack the tumour and its microenvironment. CERTO is a multicentre, controlled, open-label phase II study (NCT00842712) for pts with histologically confirmed newly diagnosed advanced NSCLC.

Methods

Pts were initially randomised 1:1:1 to receive cetuximab plus platinum-based chemotherapy alone (CTRL), or combined with CIL 2000 mg 1x/week (CIL1W) or 2x/week (CIL2W). During the study, an amendment triggered by cetuximab data from the FLEX study led to enrolment only of pts with EGFR histoscore ≥200, and closure of CIL2W due to feasibility issues. Primary endpoint was progression-free survival (PFS; independent read); secondary endpoints included overall survival (OS), safety, and biomarker analyses.

Results

Overall, 220 pts were randomised: 85 to CIL1W; 51 to CIL2W; and 84 to CTRL. Baseline characteristics were balanced. Median PFS (independent read, ITT) was 6.2 mo in CIL1W vs 5.0 mo in CTRL (HR 0.72 [95% CI, 0.49, 1.05]; p = 0.085). For pts with EGFR ≥200, median PFS was 6.8 mo in CIL1W vs 5.6 mo in CTRL (HR 0.57 [95% CI, 0.32, 0.99], p = 0.045). Investigator-read PFS was not different between CIL1W and CTRL in either population. Median OS was 13.6 vs 9.7 mo in CIL1W vs CTRL, respectively (ITT; HR 0.81 [95% CI, 0.56, 1.17]; p = 0.265); in pts with EGFR ≥200 no difference between CIL1W vs CTR for OS was found. Generally, no relevant differences between adverse events across treatment arms were reported; nausea (56%), neutropaenia (49%), and anaemia (37%) were the most frequent, and there was no increased incidence of thromboembolic events or haemorrhages in CIL-treated pts. Biomarker sample size was small, but αvß3 and αvß5 expression did not reveal a prognostic correlation to PFS or OS, and was not predictive of treatment outcome.

Conclusions

A benefit for addition of CIL1W to cetuximab and chemotherapy was seen for independent-read PFS, and a HR 0.81 for OS, equivalent to a 3.9 mo median survival improvement in favour of the combination, but no consistent efficacy was shown with CIL vs CTRL. The safety profile did not reveal any safety concerns for CIL.

Disclosure

J.F. Vansteenkiste: Advisory board: advisory functions for Merck-Serono; F. Barlesi: Corporate-sponsored research: Merck; J. Bennouna: Advisory Board: Roche, Boehringer Ingelheim and Novartis; E. Goekkurt: Advisory board: Merck; H. Lena: Advisory board: Merck; C. Hicking: Ownership: Stock Ownership Merck KGaA Other substantive relationships: Employee of trial sponsor; J. Straub: Other substantive relationships:: Employee of the trial Merck; M. Picard: Other substantive relationships: Employee of the trial sponsor; W. Schuette: Advisory Board: Merck, Amgen, AstraZeneca, Roche Corporate-sponsored research: Roche, Lilly, AstraZeneca, Amgen, Genentech, Daiichi Sankyo; K. O' Byrne: Advisory board: for cetuximab non small lung cancer Corporate-sponsored research: Grant received for clinical trial which was completed 5 years ago Other substantive relationships: Honoraria for speaker bureau lectures. All other authors have declared no conflicts of interest.