Randomized Phase II Trial of Parsatuzumab (Anti-EGFL7) or Placebo in Combination with Carboplatin, Paclitaxel, and Bevacizumab for First-Line Nonsquamous Non-Small Cell Lung Cancer

Author:

von Pawel Joachim1,Spigel David R.2,Ervin Thomas3,Losonczy György4,Barlesi Fabrice567,Juhász Erzsébet8,Anderson Maria9,McCall Bruce9,Wakshull Eric9,Hegde Priti9,Ye Weilan9,Chen Daniel9,Chang Ilsung9,Rhee Ina9,Reck Martin10

Affiliation:

1. Asklepios Fachkliniken GmbH, Gauting, Germany

2. Tennessee Oncology, Nashville, Tennessee, USA

3. Florida Cancer Specialists, Tampa, Florida, USA

4. Semmelweis Egyetem, Budapest, Hungary

5. Aix Marseille University, Marseille, France

6. Assistance Publique Hôpitaux de Marseille, Marseille, France

7. Hôpital Nord, Oncologie Multidisciplinaire et Innovations Thérapeutiques dpt, Marseille, France

8. Országos Korányi TBC és Pulmonológiai Intézet, Budapest, Hungary

9. Genentech, Inc., South San Francisco, California, USA

10. LungenClinic Grosshansdorf, Airway Research Center North (ARCN), German Center for Lung Research (DZL), Grosshansdorf, Germany

Abstract

Abstract Lessons Learned The lack of efficacy associated with anti-EGFL7 combined with standard bevacizumab and chemotherapy in this phase II trial in non-small cell lung carcinoma is consistent with the lack of benefit observed in colorectal carcinoma, highlighting the challenge of enhancing the efficacy of VEGF inhibition in unselected populations. Future efforts with agents like anti-EGFL7 should be guided by advances in pharmacodynamic and predictive biomarker development for antiangiogenic agents. Background Epidermal growth factor-like domain 7 (EGFL7) is an extracellular matrix-associated protein that is upregulated during angiogenesis and supports endothelial cell survival. This phase II trial evaluated the efficacy of the anti-EGFL7 antibody, parsatuzumab, in combination with bevacizumab plus platinum-based therapy for advanced or recurrent nonsquamous non-small cell lung cancer (NS-NSCLC). Methods Patients (n = 104) were randomized to either placebo or parsatuzumab (600 mg) in combination with bevacizumab (15 mg/kg) and carboplatin/paclitaxel, administered on day 1 of each 21-day cycle. Carboplatin and paclitaxel were administered for up to six cycles. Bevacizumab and parsatuzumab/placebo were administered for a maximum of 24 months. Results The progression-free survival (PFS) hazard ratio (HR) was 1.7 (95% confidence interval [CI], 1.0–2.8; p = .047). The median PFS was 6.7 months for the parsatuzumab arm versus 8.1 months for the placebo arm. The hazard ratio for overall survival (OS) was 1.1 (95% CI, 0.5–2.2; p = .847). The objective response rate (ORR) was 29% in the parsatuzumab arm and 56% in the placebo arm. Overall safety and tolerability were consistent with the established toxicity profile of bevacizumab. Conclusion There was no evidence of efficacy for the addition of parsatuzumab to the combination of bevacizumab and chemotherapy for first-line NS-NSCLC.

Publisher

Oxford University Press (OUP)

Subject

Cancer Research,Oncology

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