Spotlight on bevacizumab and its potential in the treatment of malignant pleural mesothelioma: the evidence to date

Figures & data

Figure 1 Inhibition of VEGF signaling in MPM.

Notes: VEGF is expressed by MPM cells and binds VEGFR. VEGFR activity increases MPM cell proliferation and together with other receptors, such as PDGFR and FGFR, controls angiogenesis. Bevacizumab binds to VEGF and prevents VEGFR activation. A number of small-molecule tyrosine kinase inhibitors block VEGFR activity as well as the activity of other receptors such as PDGFR and FGFR.
Abbreviations: FGFR, fibrocyte growth factor receptor; MPM, malignant pleural mesothelioma; PDGFR, platelet-derived growth factor receptor; TKIs, tyrosine kinase inhibitors; VEGF, vascular endothelial growth factor; VEGFR, VEGF receptor.

Table 1 Efficacy of bevacizumab-based combinations across MPM trials

First author	Jackman et al^Citation26	Kindler et al^Citation27		Ceresoli et al^Citation29	Dowell et al^Citation30	Zalcman et al^Citation31
Treatment	Bev + erlotinib	Gem + cis		Carbo + pem + bev	Cis + pem + bev (MPM patients)	Cis + pem
		+Bev	−Bev			+Bev	−Bev
PFS (months)	2.2a	6.9	6.0	6.9	6.9	9.2	7.3
OS (months)	5.8	15.6	14.7	15.3	14.8	18.8	16.1

Note:

a Only median time to progression was reported.

Abbreviations: bev, bevacizumab; carbo, carboplatin; cis, cisplatin; gem, gemcitabine; MPM, malignant pleural mesothelioma; OS, overall survival; pem, pemetrexed; PFS, progression-free survival.

Table 2 Toxicity of bevacizumab-based combinations across MPM trials

Toxicity, grade ≥3 (%)	Bev + erlotinib	Gem + cis		Carbo + pem + bev	Cis + pem + bev	Cis + pem
		+Bev	−Bev			+Bev	−Bev
Proteinuria	0	6	2	NR	NR	NR	NR
VTE	8	17	9	NR	14a	4	1
Arterial thrombosis	NR	2	0	1	2	2	0
Bleeding	0	8	2	1	NR	1	0
Hypertension	NR	23	9	3	6	23	0
Visceral perforation	NR	0	0	4	NR	0	0
Small bowel obstruction	NR	NR	NR	NR	2	NR	NR
RPLS	NR	NR	NR	NR	2	NR	NR
Cardiovascular adverse eventsb	NR	NR	NR	NR	NR	29	1

Notes:

a Toxicity grade not reported;

b cardiovascular adverse events not defined.

Abbreviations: bev, bevacizumab; carbo, carboplatin; cis, cisplatin; gem, gemcitabine; NR, not reported; pem, pemetrexed; MPM, malignant pleural mesothelioma; RPLS, reversible posterior leukoencephalopathy; VTE, venous thromboembolism.

JackmanDMKindlerHLYeapBYErlotinib plus bevacizumab in previously treated patients with malignant pleural mesotheliomaCancer2008113480881418543326

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KindlerHLKarrisonTGGandaraDRMulticenter, double-blind, placebo-controlled, randomized phase II trial of gemcitabine/cisplatin plus bevacizumab or placebo in patients with malignant mesotheliomaJ Clin Oncol201230202509251522665541

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CeresoliGLZucaliPAMencoboniMPhase II study of pemetrexed and carboplatin plus bevacizumab as first-line therapy in malignant pleural mesotheliomaBr J Cancer2013109355255823860535

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DowellJEDunphyFRTaubRNA multicenter phase II study of cisplatin, pemetrexed, and bevacizumab in patients with advanced malignant mesotheliomaLung Cancer201277356757122770372

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ZalcmanGMazieresJMargeryJBevacizumab for newly diagnosed pleural mesothelioma in the Mesothelioma Avastin Cisplatin Pemetrexed Study (MAPS): a randomised, controlled, open-label, phase 3 trialLancet2016387100261405141426719230

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