Cilengitide combined with cetuximab and platinum-based chemotherapy as first-line treatment in advanced non-small-cell lung cancer (NSCLC) patients: results of an open-label, randomized, controlled phase II study (CERTO).

Abstract

BACKGROUND:

This multicentre, open-label, randomized, controlled phase II study evaluated cilengitide in combination with cetuximab and platinum-based chemotherapy, compared with cetuximab and chemotherapy alone, as first-line treatment of patients with advanced non-small-cell lung cancer (NSCLC).

PATIENTS AND METHODS:

Patients were randomized 1:1:1 to receive cetuximab plus platinum-based chemotherapy alone (control), or combined with cilengitide 2000 mg 1×/week i.v. (CIL-once) or 2×/week i.v. (CIL-twice). A protocol amendment limited enrolment to patients with epidermal growth factor receptor (EGFR) histoscore ≥200 and closed the CIL-twice arm for practical feasibility issues. Primary end point was progression-free survival (PFS; independent read); secondary end points included overall survival (OS), safety, and biomarker analyses. A comparison between the CIL-once and control arms is reported, both for the total cohorts, as well as for patients with EGFR histoscore ≥200.

RESULTS:

There were 85 patients in the CIL-once group and 84 in the control group. The PFS (independent read) was 6.2 versus 5.0 months for CIL-once versus control [hazard ratio (HR) 0.72; P = 0.085]; for patients with EGFR histoscore ≥200, PFS was 6.8 versus 5.6 months, respectively (HR 0.57; P = 0.0446). Median OS was 13.6 for CIL-once versus 9.7 months for control (HR 0.81; P = 0.265). In patients with EGFR ≥200, OS was 13.2 versus 11.8 months, respectively (HR 0.95; P = 0.855). No major differences in adverse events between CIL-once and control were reported; nausea (59% versus 56%, respectively) and neutropenia (54% versus 46%, respectively) were the most frequent. There was no increased incidence of thromboembolic events or haemorrhage in cilengitide-treated patients. αvβ3 and αvβ5 expression was neither a predictive nor a prognostic indicator.

CONCLUSIONS:

The addition of cilengitide to cetuximab/chemotherapy indicated potential clinical activity, with a trend for PFS difference in the independent-read analysis. However, the observed inconsistencies across end points suggest additional investigations are required to substantiate a potential role of other integrin inhibitors in NSCLC treatment.

CLINICAL TRIAL REGISTRATION ID NUMBER:

NCT00842712.

• Authors: J Vansteenkiste, F Barlesi, C F Waller, J Bennouna, C Gridelli, E Goekkurt, D Verhoeven, A Szczesna, M Feurer, J Milanowski, P Germonpre, H Lena, D Atanackovic, M Krzakowski, C Hicking, J Straub, M Picard, W Schuette, K O'Byrne
• Journal: Annals of oncology : official journal of the European Society for Medical Oncology (Ann Oncol) Vol. 26 Issue 8 Pg. 1734-40 (Aug 2015) ISSN: 1569-8041 [Electronic] England
• PMID: 25939894 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: © The Author 2015. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: [email protected].

Chemical References

• Integrin alphaVbeta3
• Receptors, Vitronectin
• Snake Venoms
• integrin alphaVbeta5
• Deoxycytidine
• Cilengitide
• Vinblastine
• EGFR protein, human
• ErbB Receptors
• Cetuximab
• Cisplatin
• Vinorelbine
• Gemcitabine

Topics

• Adenocarcinoma (drug therapy, metabolism, pathology)
• Adult
• Aged
• Aged, 80 and over
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Carcinoma, Non-Small-Cell Lung (drug therapy, metabolism, pathology)
• Carcinoma, Squamous Cell (drug therapy, metabolism, pathology)
• Cetuximab (administration & dosage)
• Cisplatin (administration & dosage)
• Deoxycytidine (administration & dosage, analogs & derivatives)
• Disease-Free Survival
• ErbB Receptors (metabolism)
• Female
• Humans
• Integrin alphaVbeta3 (metabolism)
• Lung Neoplasms (drug therapy, pathology)
• Male
• Middle Aged
• Prognosis
• Proportional Hazards Models
• Receptors, Vitronectin (metabolism)
• Snake Venoms (administration & dosage)
• Treatment Outcome
• Vinblastine (administration & dosage, analogs & derivatives)
• Vinorelbine
• Gemcitabine