Article

Phase II Study of Efficacy and Safety of Bevacizumab in Combination With Chemotherapy or Erlotinib Compared With Chemotherapy Alone for Treatment of Recurrent or Refractory Non–Small-Cell Lung Cancer

University of Pittsburgh, Pittsburgh, Pennsylvania, United States
Journal of Clinical Oncology (Impact Factor: 18.43). 11/2007; 25(30):4743-50. DOI: 10.1200/JCO.2007.12.3026
Source: PubMed

ABSTRACT Bevacizumab, a humanized anti-vascular endothelial growth factor monoclonal antibody, and erlotinib, a reversible, orally available epidermal growth factor receptor tyrosine kinase inhibitor, have demonstrated evidence of a survival benefit in the treatment of non-small-cell lung cancer (NSCLC). A single-arm phase I and II study of bevacizumab plus erlotinib demonstrated encouraging efficacy, with a favorable safety profile.
A multicenter, randomized phase II trial evaluated the safety of combining bevacizumab with either chemotherapy (docetaxel or pemetrexed) or erlotinib and preliminarily assessed these combinations versus chemotherapy alone, as measured by progression-free survival (PFS). All patients had histologically confirmed nonsquamous NSCLC that had progressed during or after one platinum-based regimen.
One hundred twenty patients were randomly assigned and treated. No unexpected adverse events were noted. Fewer patients (13%) in the bevacizumab-erlotinib arm discontinued treatment as a result of adverse events than in the chemotherapy alone (24%) or bevacizumab-chemotherapy (28%) arms. The incidence of grade 5 hemorrhage in patients receiving bevacizumab was 5.1%. Although not statistically significant, relative to chemotherapy alone, the risk of disease progression or death was 0.66 (95% CI, 0.38 to 1.16) among patients treated with bevacizumab-chemotherapy and 0.72 (95% CI, 0.42 to 1.23) among patients treated with bevacizumab-erlotinib. One-year survival rate was 57.4% for bevacizumab-erlotinib and 53.8% for bevacizumab-chemotherapy compared with 33.1% for chemotherapy alone.
Results for PFS and overall survival favor combination of bevacizumab with either chemotherapy or erlotinib over chemotherapy alone in the second-line setting. No unexpected safety signals were noted. The rate of fatal pulmonary hemorrhage was consistent with previous bevacizumab trials. The toxicity profile of the bevacizumab-erlotinib combination is favorable compared with either chemotherapy-containing group.

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    • "Combining bevacizumab with erlotinib has shown promising activity in second-line treatment [20] [21]. Preclinical and clinical trial data suggest the combination of erlotinib and bevacizumab has similar efficacy to standard platinum-based chemotherapy plus bevacizumab (median PFS of 6.2–6.3 months) but with reduced toxicity [22] [23]. "
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    ABSTRACT: Molecularly targeted agents for non-small cell lung cancer (NSCLC) can provide similar efficacy to chemotherapy without chemotherapy-associated toxicities. Combining two agents with different modes of action could further increase the efficacy of these therapies. The TASK study evaluated the efficacy and safety of the epidermal growth factor receptor tyrosine kinase inhibitor erlotinib in combination with the anti-angiogenic agent bevacizumab as first-line therapy in unselected, advanced non-squamous NSCLC patients.
    Lung cancer (Amsterdam, Netherlands) 08/2013; 82(2). DOI:10.1016/j.lungcan.2013.08.002 · 3.74 Impact Factor
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    • "Our search yielded a total of 213 potentially relevant studies of bevacizumab, of which 159 were initially excluded for not meeting the inclusion criteria. After evaluating each remaining study, 22 RCTs were selected for the meta-analysis (Hurwitz et al., 2005; Sandler et al., 2006; Escudier et al., 2007; Herbst et al., 2007; Karrison et al., 2007; Miller et al., 2007; Allegra et al., 2009; Baar et al., 2009; Moehler et al., 2009; Reck et al., 2009; Robert et al., 2009; Van Cutsem et al., 2009; Brufsky et al., 2010; Burger et al., 2010; Kang et al., 2010; Kelly et al., 2010; Kindler et al., 2010; Miles et al., 2010; Okines et al., 2010; Rini et al., 2010; Tebbutt et al., 2010; Zalcman et al., 2010). The selection process is summarized in Figure 1 "
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    ABSTRACT: Bevacizumab has been approved for use in combination with chemotherapy to treat many types of cancer but associated neutropenic events, including febrile neutropenia, have been reported. To estimate the incidence and relative risk of neutropenic events in cancer patients treated with bevacizumab combination therapy, we searched PubMed, EMBASE, and Web of Science literature databases, as well as abstracts presented at the American Society of Clinical Oncology conferences, to identify relevant studies published from January 1966 to December 2011. Studies that compared bevacizumab plus chemotherapy or biological therapy with chemotherapy or biological therapy alone, and that had adequate safety data profiles, were selected for analysis. Statistical analyses were conducted to calculate the summary incidence rates, relative risks (RRs), and 95% confidence intervals (CIs) using fixed- or random-effects models. A total of 22 clinical trials involving 15,056 patients were included in the analysis. The summary incidences of high-grade neutropenia (HGN) and high-grade febrile neutropenia (HGFN) in patients receiving bevacizumab was 27.3% (95% CI: 26.4%-28.3%) and 3.91% (95% CI: 3.51%-4.37%), respectively. The risks of HGN (RR=1.10; 95% CI: 1.02-1.19; P=0.02) and HGFN (RR=1.31; 95% CI: 1.08-1.59; P=0.005) were significantly increased in bevacizumab-treated patients, compared to those who did not receive bevacizumab. The RR of bevacizumab-associated HGN, but not HGFN, varied significantly with tumor types (P=0.005). The increased risk of bevacizumab-associated neutropenic events was dose-dependent, as the RR was greater at a dose of 5 mg/kg/week than at 2.5 mg/kg/week. Our findings suggest that bevacizumab addition to cancer therapy significantly increases the risk of serious neutropenic events, and this risk may be dose-dependent.
    Asian Pacific journal of cancer prevention: APJCP 04/2013; 14(4):2453-2459. DOI:10.7314/APJCP.2013.14.4.2453 · 2.51 Impact Factor
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    • "In NSCLC, treatment with the anti-EGFR monoclonal antibody cetuximab in combination with cisplatin/vinorelbine resulted in improved overall survival compared with cisplatin/vinorelbine alone [11]. In a study in advanced NSCLC, the 1-year survival rate of patients receiving bevacizumab plus the EGFR inhibitor erlotinib was similar to that observed in those treated with bevacizumab and chemotherapy [12]. In each of these studies, the addition of a targeted agent was superior to chemotherapy alone. "
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    ABSTRACT: Purpose. The aim of this study was to assess the safety and tolerability of motesanib (an orally administered small-molecule antagonist of vascular endothelial growth factor receptors 1, 2, and 3, platelet-derived growth factor receptor, and Kit) when administered in combination with panitumumab, gemcitabine, and cisplatin. Methods. This was an open-label, multicenter phase 1b study in patients with advanced solid tumors with an ECOG performance status ≤1 and for whom a gemcitabine/cisplatin regimen was indicated. Patients received motesanib (0 mg [control], 50 mg once daily [QD], 75 mg QD, 100 mg QD, 125 mg QD, or 75 mg twice daily [BID]) with panitumumab (9 mg/kg), gemcitabine (1250 mg/m2) and cisplatin (75 mg/m2) in 21-day cycles. The primary endpoint was the incidence of dose-limiting toxicities (DLTs). Results. Forty-one patients were enrolled and received treatment (including 8 control patients). One of eight patients in the 50 mg QD cohort and 5/11 patients in the 125 mg QD cohort experienced DLTs. The maximum tolerated dose was established as 100 mg QD. Among patients who received motesanib (n = 33), 29 had motesanib-related adverse events. Fourteen patients had serious motesanib-related events. Ten patients had motesanib-related venous thromboembolic events and three had motesanib-related arterial thromboembolic events, two of which were considered serious. One patient had a complete response and nine had partial responses as their best objective response. Conclusions. The combination of motesanib, panitumumab, and gemcitabine/cisplatin could not be administered consistently and, at the described doses and schedule, may be intolerable. However, encouraging antitumor activity was noted in some cases.
    Journal of Oncology 04/2011; 2011:853931. DOI:10.1155/2011/853931
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