Anti-cancer activity of dose-fractioned mPE +/- bevacizumab regimen is paralleled by immune-modulation in advanced squamous NSLC patients

Pierpaolo Pastina, Valerio Nardone, Stefania Croci, Giuseppe Battaglia, Francesca Vanni, Cristiana Bellan, Marcella Barbarino, Veronica Ricci, Susan Costantini, Francesca Capone, Cirino Botta, Mayra Rachele Zarone, Gabriella Misso, Mariarosaria Boccellino, Michele Caraglia, Antonio Giordano, Piero Paladini, Pierfrancesco Tassone, Pierosandro Tagliaferri, Maria Grazia CusiLuigi Pirtoli, Pierpaolo Correale

Research output: Contribution to journalArticlepeer-review


Background: Results from the BEVA2007 trial, suggest that the metronomic chemotherapy regimen with dose-fractioned cisplatin and oral etoposide (mPE) +/- bevacizumab, a monoclonal antibody to the vascular endothelial growth factor (VEGF), shows anti-angiogenic and immunological effects and is a safe and active treatment for metastatic non-small cell lung cancer (mNSCLC) patients. We carried out a retrospective analysis aimed to evaluate the antitumor effects of this treatment in a subset of patients with squamous histology. Methods: Retrospective analysis was carried out in a subset of 31 patients with squamous histology enrolled in the study between September 2007 and September 2015. All of the patients received chemotherapy with cisplatin (30 mg/sqm, days 1-3q21) and oral etoposide (50 mg, days 1-15q21) (mPE) and 14 of them also received bevacizumab 5 mg/kg on the day 3q21 (mPEBev regimen). Results: This treatment showed a disease control rate of 71% with a mean progression free survival (PFS) and overall survival (OS) of 13.6 and 17 months respectively. After 4 treatment courses, 6 patients showing a remarkable tumor shrinkage, underwent to radical surgery, attaining a significant advantage in term of survival (P=0.048). Kaplan-Meier and log-rank test identified the longest survival in patients presenting low baseline levels in neutrophil-to-lymphocyte ratio (NLR) (P=0.05), interleukin (IL) 17A (P=0.036), regulatory-T-cells (Tregs) (P=0.020), and activated CD83+ dendritic cells (DCs) (P=0.03). Conclusions: These results suggest that the mPE +/- bevacizumab regimen is feasible and should be tested in comparative trials in advanced squamous-NSCLC (sqNSCLC). Moreover, its immune-biological effects strongly suggest the investigation in sequential combinations with immune check-point inhibitors.

Original languageEnglish
Pages (from-to)3123-3131
Number of pages9
JournalJournal of Thoracic Disease
Issue number9
Publication statusPublished - Sep 1 2017


  • Bevacizumab
  • Cisplatin
  • Etoposide
  • Metronomic chemotherapy
  • Squamous-NSCLC (sqNSCLC)

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine


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