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)
Mené sur 169 patients atteints d'un cancer avancé du poumon non à petites cellules, cet essai de phase II évalue l'efficacité, du point de vue de la survie sans progression, et la toxicité de l'ajout du cilengitide à un traitement combinant le cétuximab et une chimiothérapie à base de sels de platine
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 for patients with advanced 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 1x/week i.v. (CIL-once) or 2x/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 endpoint was progression-free survival (PFS; independent read); secondary endpoints 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 vs. 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 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 endpoints suggest additional investigations are required to substantiate a potential role of other integrin inhibitors in NSCLC treatment.