First-line erlotinib and bevacizumab in patients with locally advanced and/or metastatic non-small-cell lung cancer: a phase II study including molecular imaging

Dingemans, A.; Langen, Adrianus J. de; Boogaart, V. van den; Marcus, J. Tim; Backes, Walter H.; Scholtens, Harmannus; Tinteren, Harm van; Hoekstra, Otto S.; Pruim, Jan; Brans, Boudewijn; Thunnissen, Erik; Smit, Egbert F.; Groen, Harry J.M.

doi:10.1093/annonc/mdq391

Cited by 70 publications

(36 citation statements)

References 41 publications

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“…The primary endpoint of the study was the disease control rate (DCR), defined as the rate of subjects with no progression (based on RECIST 1.0) after 6 weeks of treatment (12)(13)(14). To be able to discontinue the trial early if the treatment showed insufficient activity, a 2-stage design was implemented (Simon optimal design; p0…”

Section: Statisticsmentioning

confidence: 99%

A Phase II Study of Sorafenib in Patients with Platinum-Pretreated, Advanced (Stage IIIb or IV) Non–Small Cell Lung Cancer with a KRAS Mutation

Dingemans

Mellema

Groen

et al. 2013

Clinical Cancer Research

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Purpose: Sorafenib inhibits the Ras/Raf pathway, which is overactive in cancer patients with a KRAS mutation. We hypothesized that patients with non-small cell lung cancer (NSCLC) with KRAS mutation will benefit from treatment with sorafenib.Experimental Design: In this phase II study, patients with KRAS-mutated, stage IIIb or IV NSCLC that progressed after at least one platinum-containing regimen were treated with sorafenib.

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Section: Statisticsmentioning

confidence: 99%

A Phase II Study of Sorafenib in Patients with Platinum-Pretreated, Advanced (Stage IIIb or IV) Non–Small Cell Lung Cancer with a KRAS Mutation

Dingemans

Mellema

Groen

et al. 2013

Clinical Cancer Research

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show abstract

“…Previous studies have shown that NPR, used as a study endpoint, can predict clinical benefit in cancer patients. [13][14][15] When designing this study, we presumed that the NPR could be improved from 64% in the PC group to 84% after 12 wk (almost 4 cycles) of PC-G treatment. Our results showed that the intercalated addition of gefitinib did not improve the treatment outcomes not only with regard to NPR but also with regard to ORR, PFS, or OS.…”

Section: Discussionmentioning

confidence: 99%

A phase II randomized trial evaluating gefitinib intercalated with pemetrexed/platinum chemotherapy or pemetrexed/platinum chemotherapy alone in unselected patients with advanced non-squamous non-small cell lung cancer

Zhang

et al. 2014

Cancer Biology & Therapy

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“…In theory, administering bevacizumab and erlotinib together may have additional clinical benefits because bevacizumab and erlotinib act on two different pathways. Combination of bevacizumab and erlotinib was well tolerated in clinical trials but did not improve OS (Table 3) [50][51][52][53]. The recent phase III trial ATLAS, assessing bevacizumab and erlotinib met its primary endpoint with a significant (28%) decrease in the risk of progression and an increase in the median PFS of 1.1 months comparing with erlotinib alone [54].…”

Section: Targeted Therapymentioning

confidence: 99%

Monoclonal Antibodies: An Emerging Class of Therapeutics in Non Small Cell Lung Cancer

Guilleminault¹,

Lemarié²,

Heuzé-Vourc’h³

2012

JCT

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Lung cancer is the leading cause of cancer-related deaths in industrialized countries and non small cell lung cancer (NSCLC) accounts for 85% of all lung cancers. Cisplatin doublet based chemotherapy, which is the recommended regimen in first line therapy in advanced or metastatic NSCLC, improves survival but in low proportion. Monoclonal antibodies (mAbs) are a novel promising therapeutic class used with great results in inflammatory diseases such as rheumatoid arthritis. Antibodies are natural proteins with modular structure, specific pharmacodynamics and pharmacokinetics and possibly produced against any antigens, thus giving them several advantages over small drug therapeutics. In solid tumors, therapeutic mAbs improved progression free survival (PFS) and overall survival (OS) of patients with breast and colon cancers and had considerably changed the treatment in clinical practice. In NSCLC, bevacizumab, an anti-VEGF mAb, and cetuximab, an anti-EGFR mAb, are the most studied antibodies. Bevacizumab acts on angiognenesis and improved PFS of non squamous NSCLC but in low proportion as shown in two large phase III trials. It was approved by European Medicines Agency (EMEA) and Food and Drug administration (FDA) as a first line therapy in combination with cisplatin doublet chemotherapy. Cetuximab slightly enhanced OS but did not improve PFS in two large phase III trials. These results added to high adverse effect lead to cetuximab refusal by EMEA and FDA in NSCLC. At first glance, the results of mAbs in NSCLC are somewhat disappointing, in contrast to the benefits obtained with mAb treatments in other solid tumors. However, many other mAbs directed against novel targets, such as IGF1-R or CTLA-4, and new mAbs targeting VEGFR and EGFR pathways with different pharmacodymamical and pharmacokinetic properties are under evaluation and may change our vision of taking care of patients with NSCLC. In conclusion, it seems that mAbs therapy in NSCLC clearly marks the start of a new era in NSCLC treatment, with promises in improving patient survival and quality of life.

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First-line erlotinib and bevacizumab in patients with locally advanced and/or metastatic non-small-cell lung cancer: a phase II study including molecular imaging

Abstract: First-line treatment with bevacizumab and erlotinib in stage IIIb/IV NSCLC resulted in an NPR of 75%. OS was however disappointing. Early response evaluation with FDG-PET is the best predictive test for PFS.

Cited by 70 publications

References 41 publications

A Phase II Study of Sorafenib in Patients with Platinum-Pretreated, Advanced (Stage IIIb or IV) Non–Small Cell Lung Cancer with a KRAS Mutation

A Phase II Study of Sorafenib in Patients with Platinum-Pretreated, Advanced (Stage IIIb or IV) Non–Small Cell Lung Cancer with a KRAS Mutation

A phase II randomized trial evaluating gefitinib intercalated with pemetrexed/platinum chemotherapy or pemetrexed/platinum chemotherapy alone in unselected patients with advanced non-squamous non-small cell lung cancer

Monoclonal Antibodies: An Emerging Class of Therapeutics in Non Small Cell Lung Cancer

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