Corrections to “Phase I/IIa study evaluating the safety, efficacy, pharmacokinetics, and pharmacodynamics of lucitanib in advanced solid tumors”

Soria, Jean Charles; DeBraud, F.; Bahleda, Rastilav; Adamo, Bárbara; Varga, Andrea; Dienstmann, R.; Delmonte, Angelo; Cereda, Roberta; Isaacson, Jeff; Litten, Jason B.; Allen, Andrew R.; Dubois, Frédéric; Saba, Corey; Robert, Renata; D’Incalci, Maurizio; Zucchetti, Massimo; Camboni, Maria Gabriella; Tabernero, Josep

doi:10.1093/annonc/mdu547

Cited by 10 publications

(12 citation statements)

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“…Interestingly, we only observed FGFR1 gene amplification in HPV-negative HNSCC, which was also found in large scale genomic studies. Whether this subgroup may respond to FGFR inhibitors should be investigated in HNSCC clinical trials, as FGFR1-amplified breast tumors responded well to dovitinib and lucitanib in clinical trials (20,21).…”

Section: Discussionmentioning

confidence: 99%

“…[16][17][18][19]. Several multikinase inhibitors targeting FGFR and other kinases, for example, dovitinib and lucitanib, have already shown great therapeutic potential in clinical studies on FGFRaberrated breast cancer and various other advanced solid tumors (20,21). A novel selective and potent pan-FGFR inhibitor AZD4547 is currently tested in phase II clinical trials on various types of cancer (ClinicalTrials.gov identifier: NCT01795768, NCT01791985).…”

Section: Introductionmentioning

confidence: 99%

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FGFR1 Is a Potential Prognostic Biomarker and Therapeutic Target in Head and Neck Squamous Cell Carcinoma

Koole

Brunen

Kempen

et al. 2016

Clinical Cancer Research

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Purpose: FGFR1 is a promising therapeutic target in multiple types of solid tumors, including head and neck squamous cell carcinoma (HNSCC). FGFR inhibitors have shown great therapeutic value in preclinical models. However, resistance remains a major setback. In this study, we have investigated the prognostic value of FGFR1 expression in HNSCC, the therapeutic relevance of targeting FGFR with AZD4547, and potential resistant mechanisms.Experimental Design: IHC and FISH were applied on tissue microarrays to investigate FGFR1 protein expression and FGFR1 gene copy numbers in 452 HNSCCs. The sensitivity of HNSCC cell lines to AZD4547, either as single or combination treatment with the EGFR inhibitor gefitinib, was assessed using long-term colony formation assays, short-term viability assays, and biochemical analysis.Results: FGFR1 protein overexpression occurred in 82% (36/ 44) of human papillomavirus (HPV)-positive HNSCC and 75% (294/392) of HPV-negative HNSCC and relates with poor overall survival and disease-free survival in HPV-negative HNSCC [HR, 3.07; 95% confidence interval (CI), 1.74-6.90; P ¼ 0.001 and HR, 1.53; 95% CI, 1.04-2.39; P ¼ 0.033]. Moreover, the FGFR1 gene was amplified in 3% (3/110) of HPV-negative HNSCC. Treatment of the high FGFR1-expressing cell line CCL30 with AZD4547 reduced cell proliferation and FGFR signaling. Two FGFR-amplified cell lines, SCC147 and BICR16, were resistant to AZD4547 treatment due to EGFR signaling. Combined AZD4547 and gefitinib treatment synergistically inhibited the proliferation of resistant cell lines.Conclusions: Here, we identify high FGFR1 expression as a candidate prognostic biomarker in HPV-negative HNSCC. Furthermore, we provide a rationale for treating FGFR1-expressing HNSCC with the FGFR inhibitor AZD4547 and for combining AZD4547 and gefitinib in FGFR inhibitor-resistant HNSCC patients. Clin Cancer Res; 22(15); 3884-93. Ó2016 AACR.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

FGFR1 Is a Potential Prognostic Biomarker and Therapeutic Target in Head and Neck Squamous Cell Carcinoma

Koole

Brunen

Kempen

et al. 2016

Clinical Cancer Research

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“…The most common adverse effects were proteinuria, hypertension and asthenia (Soria et al, 2014). In a phase I/II clinical trial it has been tested in several tumors such as breast, colon, lung and thyroid, the Maximum Tolerated Dose (MTD) being 15 mg a day.…”

Section: Lucitanibmentioning

confidence: 99%

FGFR a promising druggable target in cancer: Molecular biology and new drugs

Porta

Borea²,

Coelho³

et al. 2017

Critical Reviews in Oncology/Hematology

174

162

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Introduction The Fibroblast Growth Factor Receptor (FGFR) family consists of Tyrosine Kinase Receptors (TKR) involved in several biological functions. Recently, alterations of FGFR have been reported to be important for progression and development of several cancers. In this setting, different studies are trying to evaluate the efficacy of different therapies targeting FGFR. Areas Covered This review summarizes the current status of treatments targeting FGFR, focusing on the trials that are evaluating the FGFR profile as inclusion criteria: Multi-Target, Pan-FGFR Inhibitors and anti-FGF (Fibroblast Growth Factor)/FGFR Monoclonal Antibodies. Expert opinion Most of the TKR share intracellular signaling pathways; therefore, cancer cells tend to overcome the inhibition of one tyrosine kinase receptor by activating another. The future of TKI (Tyrosine Kinase Inhibitor) therapy will potentially come from multi-targeted TKIs that target different TKR simultaneously. It is crucial to understand the interaction of the FGF-FGFR axis with other known driver TKRs. Based on this, it is possible to develop therapeutic strategies targeting multiple connected TKRs at once. One correct step in this direction is the reassessment of multi target inhibitors considering the FGFR status of the tumor. Another opportunity arises from assessing the use of FGFR TKI on patients harboring FGFR alterations

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“…17 Nevertheless, treatment with highly specifıc and bioactive FGFR inhibitors failed to demonstrate antitumor activity in phase I trials. 18 Interestingly, multikinase inhibitors like lucitanib were associated with promising antitumor activity in patients presenting FGFR1 amplifıca-tions, 19 but whether this antitumor activity relates to FGFR inhibition is unclear. FGFR1 amplifıcation could be associated with level III evidence as a target.…”

Section: Key Pointsmentioning

confidence: 99%

Precision Medicine for Metastatic Breast Cancer

Deluche

Onesti

Varga

2015

American Society of Clinical Oncology Educational Book

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OVERVIEWGenomic studies have shown that large numbers of candidate targets are observed in breast cancer. Nevertheless, only a few of them are validated as relevant targets in clinical studies. Estrogen receptor (ER) and HER2 expressions could be associated with a level I evidence. Beyond ER and HER2, BRCA and PIK3CA mutations (when targeted with alpha-specific PI3K inhibitors) could be considered as promising targets in breast cancer since they have been associated with objective responses in phase I/II trials. In addition to these four molecular alterations, several others have shown promising results in preclinical studies and are being investigated in clinical trials. These genomic alterations include AKT1, ERBB2, and ESR1 mutations. These considerations highlight the lack of evidence for using multiplex technologies to individualize therapy in metastatic breast cancer. Sequencing multiple genes to treat metastatic breast cancer is very promising but should be done in the context of clinical trials, either to enrich phase I/II trials in patients with genomic alterations or to show medical usefulness of new biotechnologies like next-generation sequencing (NGS). Although most current approaches of precision medicine are aiming at targeting drivers, additional applications could be developed in the future. This includes the identification of DNA repair deficiencies, mechanisms of immune suppression, and identification of minority lethal subclones. Finally, one of the very promising applications of genomics for metastatic breast cancer is the identification of pathway activation or defects at the individual level. For example, gene expression and single nucleotide polymorphisms (SNP) signatures are being developed to detect kinase (such as mammalian target of rapamycin [mTOR]/CDK4) activations or DNA repair deficiencies.

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Corrections to “Phase I/IIa study evaluating the safety, efficacy, pharmacokinetics, and pharmacodynamics of lucitanib in advanced solid tumors”

Cited by 10 publications

References 0 publications

FGFR1 Is a Potential Prognostic Biomarker and Therapeutic Target in Head and Neck Squamous Cell Carcinoma

FGFR1 Is a Potential Prognostic Biomarker and Therapeutic Target in Head and Neck Squamous Cell Carcinoma

FGFR a promising druggable target in cancer: Molecular biology and new drugs

Precision Medicine for Metastatic Breast Cancer

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