Phase II study of bevacizumab, cisplatin, and docetaxel plus maintenance bevacizumab as first-line treatment for patients with advanced non-squamous non-small-cell lung cancer combined with exploratory analysis of circulating endothelial cells: Thoracic Oncology Research Group (TORG)1016

Abstract

BackgroundPreclinical studies have demonstrated that docetaxel and bevacizumab may act synergistically by decreasing endothelial cell proliferation and preventing circulating endothelial progenitor mobilization. The objective of this study was to assess the efficacy and safety of a combination therapy of bevacizumab, cisplatin, and docetaxel in chemotherapy-naive Japanese patients with advanced non-squamous non-small-cell lung cancer (NSCLC).MethodsEligible patients were chemotherapy-naive and had advanced/recurrent non-squamous NSCLC. The patients received 4 cycles of docetaxel (60 mg/m2), cisplatin (80 mg/m2), and bevacizumab (15 mg/kg) once every 3 weeks, followed by bevacizumab as maintenance therapy, every 3 weeks until disease progression or attainment of unacceptable toxicity level. The primary endpoint was objective response rate (ORR). The numbers of circulating endothelial cells (CEC) were also estimated on days 1 and 8 of the first cycle for the exploratory analysis of efficacy prediction.ResultsA total of 47 patients were enrolled from October 2010 to April 2012. Bevacizumab as maintenance therapy was administered to 41 patients (87.2%), and the median number of total treatment cycles was 9 (range: 1–36). ORR, median progression-free survival (PFS), and median overall survival of the patients were 74.5%, 9.0 months, and 27.5 months, respectively. The most common grade 3/4 adverse event was neutropenia (95.7%), followed by leukopenia (59.6%) and hypertension (46.8%). PFS was longer in patients with ≥10 count increase in CECs than that in patients with < 10 count increase in CECs (respective median PFS of 11.0 months versus 6.90 months) although the difference was not statistically significant (p = 0.074).ConclusionsA combination therapy of bevacizumab, cisplatin, and docetaxel, followed by bevacizumab as maintenance was highly effective in patients with non-squamous NSCLC despite the high incidence of grade 3/4 neutropenia. The increase in CEC count between days 1 and 8 may predict the efficacy of our bevacizumab-contained treatment regimen.Trial registrationUMIN Clinical Trial Registry; UMIN000004368. Registered date; October 11, 2010 (Retrospectively registered).Electronic supplementary materialThe online version of this article (10.1186/s12885-018-4150-y) contains supplementary material, which is available to authorized users.

A Snapshot of The Tumor Microenvironment in Colorectal Cancer: The Liquid Biopsy

“…In colorectal cancer patients, the quantification of CECs could improve the identification of early predictors of response to bevacizumab combined with FOLFOX (FOL–Folinic acid (leucovorin), F–Fluorouracil (5-FU), OX–Oxaliplatin (Eloxatin)/OXXEL (Oxaliplatin plus Xeloda) [181]. Similarly, other studies have assessed the predictive value of CECs for anticancer therapies in urothelial [201], breast [202], lung [203] and renal carcinoma [204].…”

Cell State and Cell Type: Deconvoluting Circulating Tumor Cell Populations in Liquid Biopsies by Multi-Omics

“…Circulating endothelial cells (CECs), while mainly studied in the context of vascular damage and dysfunction in cardiovascular diseases [18,19], have been proposed as a biomarker in cancer patients [20][21][22][23]. As of today, CECs have been specifically studied in patients with breast, colorectal and small-cell lung cancer (SCLC) receiving anti-angiogenic therapies, and increases in CEC counts have been associated with prolonged progression-free survival [24][25][26][27]; yet, their predictive value remains controversial [21,22]. In addition, little is known about the significance and frequency of CECs in patients with carcinomas not treated with anti-angiogenic drugs.…”