Angiogenesis Inhibitors in Small Cell Lung Cancer.

Agnese Montanino,Anna Manzo,Claudia Sandomenico,Vincenzo Sforza,Giacomo Pascarella,Alessandro Morabito,Guido Carillio,Carmine La Manna,Raffaele Costanzo,Giuliano Palumbo,Priscilla Cascetta,Maria C Piccirillo,Nicola Normanno,Giovanna Esposito,Gerardo Botti

doi:10.3389/fonc.2021.655316

Abstract

Inhibition of angiogenesis has been demonstrated to be an efficacious strategy in treating several tumors. Vascular endothelial growth factor (VEGF) is the most important protein with proangiogenic functions and it is overexpressed in small cell lung cancer (SCLC). Bevacizumab, a monoclonal antibody directed against VEGF, showed a promising activity in combination with etoposide and cisplatin as first-line treatment of patients with extended stage (ES)-SCLC and two randomized studies confirmed that bevacizumab improved PFS, but failed to prolong OS. Instead, disappointing results have been observed with endostar, sunitinib, sorafenib, vandetanib, and thalidomide in combination with chemotherapy in the first-line setting, with sunitinib in the maintenance setting, with sunitinib, cediranib and nintedanib as single agents or ziv-aflibercept in combination with topotecan in second-line setting. Only anlotinib improved OS and PFS as third-line therapy in Chinese patients with SCLC, and it was approved with this indication in China. Future challenges are the evaluation of the role of angiogenesis inhibitors in combination with immune- checkpoint inhibitors and chemotherapy in SCLC patients and the identification of predictive biomarkers of response to both agents.

Highlights

Lung cancer is the most frequent cause of tumor death worldwide
A promising activity was observed in the first-line setting with bevacizumab in combination with etoposide and cisplatin and two randomized studies confirmed that bevacizumab improved progressionfree survival (PFS), but not overall survival (OS) (SALUTE and GOIRC studies)
The scenario of treatment of small cell lung cancer (SCLC) is quickly changing in the last few years, due to the positive results observed with the combination of immune checkpoint inhibitors plus chemotherapy in the first-line setting and the recent approval by the Food and Drug Administration of lurbinectedin in patients pretreated with platinum based chemotherapy [3, 49]

Summary

INTRODUCTION

Lung cancer is the most frequent cause of tumor death worldwide. Small cell lung cancer (SCLC) accounts for 10% to 15% of all lung cancers and tobacco is a universally recognized inducing factor [1]. The drug was discontinued in half of patients due to toxicity or request to stop therapy Another phase II study was conducted with sunitinib at a lower dose (25 mg daily) as maintenance treatment in 17 patients with ES-SCLC responding to first-line chemotherapy with irinotecan (60 mg/m2, days 1, 8, 15) and carboplatin (AUC = 4, day 1) for six cycles [27]. The results of this trial were encouraging, with a median time to progression of 7.6 months from the beginning of chemotherapy and a 1-year OS of 54%. This was the first phase 2 study evaluating the combination of an immune checkpoint inhibitor with anti-VEGFR in patients with advanced SCLC and the reported positive results support further clinical studies of camrelizumab plus apatinib in SCLC

Findings

DISCUSSION

CONCLUSIONS