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https://www.readbyqxmd.com/read/28435294/patient-considerations-in-metastatic-colorectal-cancer-role-of-panitumumab
#1
REVIEW
Jane E Rogers
Epidermal growth factor receptor (EGFR) is overexpressed in many malignancies, including colorectal cancer (CRC), making EGFR an attractive treatment option. Panitumumab and cetuximab, monoclonal antibodies (mAbs) directed at EGFR, are both currently utilized in the management of metastatic CRC (mCRC). Through the development of these agents in mCRC, key issues surrounding each mAbs use have been revealed. These key issues include negative patient outcome avoidance when determining use, the economic burden with high-cost medication, predictive biomarkers, tumor location, patient geographic location, patient quality of life, and the prevention of debilitating adverse effects...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28424871/final-analysis-of-the-randomised-peak-trial-overall-survival-and-tumour-responses-during-first-line-treatment-with-mfolfox6-plus-either-panitumumab-or-bevacizumab-in-patients-with-metastatic-colorectal-carcinoma
#2
Fernando Rivera, Meinolf Karthaus, J Randolph Hecht, Isabel Sevilla, Frédéric Forget, Gianpiero Fasola, Jean-Luc Canon, Xuesong Guan, Gaston Demonty, Lee S Schwartzberg
PURPOSE: To report planned final overall (OS) and progression-free survival (PFS) analyses from the phase II PEAK trial (NCT00819780). METHODS: Patients with previously untreated, KRAS exon 2 wild-type (WT) metastatic colorectal cancer (mCRC) were randomised to mFOLFOX6 plus panitumumab or bevacizumab. The primary endpoint was PFS; secondary endpoints included OS, objective response rate, duration of response (DoR), time to response, resection and safety. Treatment effect by tumour RAS status was a prespecified objective...
April 19, 2017: International Journal of Colorectal Disease
https://www.readbyqxmd.com/read/28418176/panitumumab-conjugated-pt-drug-nanomedicine-for-enhanced-efficacy-of-combination-targeted-chemotherapy-against-colorectal-cancer
#3
Ming-Hsien Tsai, Chao-Hsuan Pan, Cheng-Liang Peng, Ming-Jium Shieh
Targeted combination chemotherapy (TCT) has recently been used to increase the induction of tumor cell death. In particular, the combination of Panitumumab and the platinum (Pt)-derived chemotherapeutic drug Oxaliplatin is clinically effective against KRAS and BRAF wild-type colorectal cancer (CRC) cells that overexpress epidermal growth factor receptors, and significantly greater efficacy is observed than with either drug alone. However, low accumulation of Pt drug in tumor sites prevents achievement of ideal efficacy...
April 18, 2017: Advanced Healthcare Materials
https://www.readbyqxmd.com/read/28404754/therapeutic-response-of-metastatic-colorectal-cancer-harboring-a-kras-missense-mutation-after-combination-chemotherapy-with-the-egfr-inhibitor-panitumumab
#4
Emil Lou, Donna D'Souza, Andrew C Nelson
Over the past decade, subset analyses of retrospective and prospective clinical studies have determined that KRAS-mutated metastatic colorectal cancers do not respond effectively to inhibition of epidermal growth factor receptor (EGFR) with the EGFR-targeting monoclonal antibodies cetuximab or panitumumab. Within the past few years, the scope of tested variants in the KRAS oncogene has expanded significantly, and testing of all RAS family genes has become more widely available in clinical laboratories. Expert consensus guidelines have recommended not using EGFR inhibitors in patients with KRAS-mutated tumors...
April 2017: Journal of the National Comprehensive Cancer Network: JNCCN
https://www.readbyqxmd.com/read/28403233/cost-effectiveness-of-cetuximab-and-panitumumab-for-chemotherapy-refractory-metastatic-colorectal-cancer
#5
Adriana Camargo Carvalho, Frederico Leal, Andre Deeke Sasse
BACKGROUND: Cetuximab and panitumumab are monoclonal antibodies targeting the epidermal growth factor receptor. Both drugs are active against RAS wild type metastatic colorectal cancer after chemotherapy failure, with similar efficacy and toxicity profiles. However, their cost and limited survival benefits may compromise incorporation in the Brazilian public healthcare system, the Unified Heath System (Sistema Único de Saúde) (SUS). METHODS: A cost-effectiveness analysis was conducted using a Markov model from the Brazilian Public health perspective and a lifetime horizon in patients with RAS -wt mCRC...
2017: PloS One
https://www.readbyqxmd.com/read/28399109/tyrosine-kinase-targeting-drugs-associated-heart-failure
#6
N Gronich, I Lavi, O Barnett-Griness, W Saliba, D R Abernethy, G Rennert
BACKGROUND: The impact of cancer therapies on cardiac disease in the general adult cancer survivor population is largely unknown. Our objective was to evaluate which tyrosine kinase-targeting drugs are associated with greater risk for new-onset heart failure (HF). METHODS: A nested case-control analysis was conducted within a cohort of 27 992 patients of Clalit Health Services, newly treated with a tyrosine kinase-targeting, and/or chemotherapeutic drug, for a malignant disease, between 1 January 2005 and 31 December 2012...
April 11, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28379722/clinical-pathways-management-of-quality-and-cost-in-oncology-networks-in-the-metastatic-colorectal-cancer-setting
#7
Peter G Ellis, Bert H O'Neil, Martin F Earle, Stephanie McCutcheon, Hans Benson, Melinda Krebs, Kathy Lokay, Amanda Barry
PURPOSE: Via Pathways (clinical pathways for cancer) provide evidence-based guidance for specific patient presentations based on the merit of efficacy, then toxicity, and finally cost (if efficacy and toxicity are comparable). We evaluated the impact of a change to the guidance in the metastatic colorectal cancer (mCRC) setting across two large, integrated health networks. METHODS: Cetuximab and panitumumab were determined to have equal efficacy in the treatment of mCRC with no significant difference in toxicity based on recent data from key clinical studies...
April 5, 2017: Journal of Oncology Practice
https://www.readbyqxmd.com/read/28375604/structure-directed-and-tailored-diversity-synthetic-antibody-libraries-yield-novel-anti-egfr-antagonists
#8
Shane Miersch, Bharathikumar Vellalore Maruthachalam, C Ronald Geyer, Sachdev S Sidhu
We tested whether grafting an interaction domain into the hypervariable loop of a combinatorial antibody library could promote targeting to a specific epitope. Formation of the epidermal growth factor receptor (EGFR) signaling heterodimer involves extensive contacts mediated by a "dimerization loop." We grafted the dimerization loop into the third hypervariable loop of a synthetic antigen-binding fragment (Fab) library and diversified other loops using a tailored diversity strategy. This structure-directed Fab library and a naı̈ve synthetic Fab library were used to select Fabs against EGFR...
April 4, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/28323034/co-targeting-of-egfr-and-autophagy-signaling-is-an-emerging-treatment-strategy-in-metastatic-colorectal-cancer
#9
Evangelos Koustas, Michalis V Karamouzis, Chrysovalantou Mihailidou, Dimitrios Schizas, Athanasios G Papavassiliou
The epidermal growth factor receptor (EGFR) and its associated pathway is a critical key regulator of CRC development and progression. The monoclonal antibodies (MoAbs) cetuximab and panitumumab, directed against EGFR, represent a major step forward in the treatment of metastatic colorectal cancer (mCRC), in terms of progression-free survival and overall survival in several clinical trials. However, the activity of anti-EGFR MoAbs appears to be limited to a subset of patients with mCRC. Studies have highlighted that acquired-resistance to anti-EGFR MoAbs biochemically converge into Ras/Raf/Mek/Erk and PI3K/Akt/mTOR pathways...
March 18, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28284575/mfolfox6-plus-panitumumab-versus-5-fu-lv-plus-panitumumab-after-six-cycles-of-frontline-mfolfox6-plus-panitumumab-a-randomized-phase-ii-study-of-patients-with-unresectable-or-advanced-recurrent-ras-wild-type-colorectal-carcinoma-sapphire-study-design-and%C3%A2-rationale
#10
Naoki Nagata, Hideyuki Mishima, Shuichi Kurosawa, Koji Oba, Junichi Sakamoto
BACKGROUND: In Japan, oxaliplatin (OXA)/5-fluorouracil (5-FU)/leucovorin (LV)-the mFOLFOX6 regimen-is the most frequently used first-line chemotherapy backbone for metastatic colorectal cancer. However, peripheral nerve disorders caused by OXA during mFOLFOX6 therapy can decrease patients' quality of life. OXA can be safely discontinued from a FOLFOX regimen after 6 cycles during first-line therapy. Also, for patients who discontinue OXA without having experienced peripheral nerve disorders, reintroducing OXA in the later stages of treatment could remain an option...
March 1, 2017: Clinical Colorectal Cancer
https://www.readbyqxmd.com/read/28282789/a-randomized-phase-iii-study-of-combining-erlotinib-with-bevacizumab-and-panitumumab-versus-erlotinib-alone-as-second-line-therapy-for-chinese-patients-with-non-small-cell-lung-cancer
#11
Ying Wang, Hui Wang, Yiling Jiang, Yaping Zhang, Xiaoyan Wang
PURPOSE: In this phase III clinical study, we assessed the clinical outcomes of combining erlotinib with bevacizumab and panitumumab as second-line chemotherapy for patients with non-small-cell lung cancer (NSCLC). METHODS: Chinese NSCLC patients, who received first-line platinum-based chemotherapy but still experienced disease progression, were assigned to receive second-line treatment of erlotinib plus bevacizumab and panitumumab (arm I), or erlotinib plus placebo (arm II)...
March 6, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28280605/next-generation-sequencing-identifies-interactome-signatures-in-relapsed-and-refractory-metastatic-colorectal-cancer
#12
Benny Johnson, Laurence Cooke, Daruka Mahadevan
BACKGROUND: In the management of metastatic colorectal cancer (mCRC), KRAS, NRAS and BRAF mutational status individualizes therapeutic options and identify a cohort of patients (pts) with an aggressive clinical course. We hypothesized that relapsed and refractory mCRC pts develop unique mutational signatures that may guide therapy, predict for a response and highlight key signaling pathways important for clinical decision making. METHODS: Relapsed and refractory mCRC pts (N=32) were molecularly profiled utilizing commercially available next generation sequencing (NGS) platforms...
February 2017: Journal of Gastrointestinal Oncology
https://www.readbyqxmd.com/read/28245681/-does-the-sidedness-determine-the-first-line-treatment-of-irresectable-metastatic-colorectal-cancer
#13
Tamás Kullmann, István Sipőcz, Tamás Pintér
INTRODUCTION AND AIM: Median life expectancy of non-resectable metastatic colorectal cancer may surpass three years. However, several points of the treatment strategy are subject of ongoing debate. Optimal sequence of targeted agents is not elucidated either. Based on retrospective analyses of six clinical studies and a metaanalysis, the superiority of anti-EGFR agents such as cetuximab and panitumumab over anti-VEGF bevacizumab has been proposed in the treatment of left sided tumours...
March 2017: Orvosi Hetilap
https://www.readbyqxmd.com/read/28242452/top-down-analysis-of-immunoglobulin-g-isotypes-1-and-2-with-electron-transfer-dissociation-on-a-high-field-orbitrap-mass-spectrometer
#14
Luca Fornelli, Daniel Ayoub, Konstantin Aizikov, Xiaowen Liu, Eugen Damoc, Pavel A Pevzner, Alexander Makarov, Alain Beck, Yury O Tsybin
The increasing importance of immunoglobulins G (IgGs) as biotherapeutics calls for improved structural characterization methods designed for these large (~150kDa) macromolecules. Analysis workflows have to be rapid, robust, and require minimal sample preparation. In a previous work we showed the potential of Orbitrap Fourier transform mass spectrometry (FTMS) combined with electron transfer dissociation (ETD) for the top-down investigation of an intact IgG1, resulting in ~30% sequence coverage. Here, we describe a top-down analysis of two IgGs1 (adalimumab and trastuzumab) and one IgG2 (panitumumab) performed with ETD on a mass spectrometer equipped with a high-field Orbitrap mass analyzer...
February 27, 2017: Journal of Proteomics
https://www.readbyqxmd.com/read/28237539/rationale-for-and-design-of-the-paradigm-study-randomized-phase-iii-study-of-mfolfox6-plus-bevacizumab-or-panitumumab-in-chemotherapy-na%C3%A3-ve-patients-with-ras-kras-nras-wild-type-metastatic-colorectal%C3%A2-cancer
#15
Takayuki Yoshino, Hiroyuki Uetake, Katsuya Tsuchihara, Kohei Shitara, Kentaro Yamazaki, Eiji Oki, Takeo Sato, Takeshi Naitoh, Yoshito Komatsu, Takeshi Kato, Kazunori Yamanaka, Kouji Iwasaki, Jumpei Soeda, Masamitsu Hihara, Takeharu Yamanaka, Atsushi Ochiai, Kei Muro
BACKGROUND: It remains unclear whether an anti-VEGF or anti-EGFR antibody with standard doublet chemotherapy is the optimal first-line treatment in patients with RAS (KRAS/NRAS) wild-type metastatic colorectal cancer (mCRC). Here we outline the PARADIGM study (NCT02394795), designed to evaluate the superiority of panitumumab over bevacizumab, in combination with oxaliplatin/5-fluorouracil/leucovorin (mFOLFOX6) in patients with RAS wild-type chemotherapy-naïve mCRC. PATIENTS AND METHODS: Eligible patients are aged 20 to 79 years with an ECOG performance status of 0-1 and histologically/cytologically confirmed RAS wild-type mCRC...
January 24, 2017: Clinical Colorectal Cancer
https://www.readbyqxmd.com/read/28229371/overall-survival-and-metastasis-resections-in-patients-with-metastatic-colorectal-cancer-using-electronic-medical-records
#16
Eetu Heervä, Maija Lavonius, Panu Jaakkola, Heikki Minn, Raija Ristamäki
PURPOSE: Treatment for patients with metastatic colorectal cancer is chemotherapy commonly combined with monoclonal antibodies against vascular endothelial growth factor (bevacizumab) or epidermal growth factor receptor (cetuximab or panitumumab), the efficacy of which has been proven in randomized controlled trials. The objective of the current retrospective study was to analyze the impact of targeted therapy, adverse events, and dose reduction on overall survival (OS) and metastasis resection rates...
February 23, 2017: Journal of Gastrointestinal Cancer
https://www.readbyqxmd.com/read/28228152/cardiac-metastasis-from-colon-cancer-effectively-treated-with-5-fluorouracil-leucovorin-and-oxaliplatin-modified-folfox6-plus-panitumumab-a-case-report
#17
Yoshiki Tsujii, Yoshito Hayashi, Akira Maekawa, Tetsuji Fujinaga, Kengo Nagai, Shunsuke Yoshii, Akihiko Sakatani, Satoshi Hiyama, Shinichiro Shinzaki, Hideki Iijima, Tetsuo Takehara
BACKGROUND: Cardiac metastasis from colorectal cancer is rare. There is little evidence supporting the effectiveness of chemotherapy, and standard therapy for metastatic cardiac tumors has not been established. CASE PRESENTATION: A 76-year-old woman presented with a right ventricle tumor that was detected incidentally on screening cardiac ultrasonography. The initial computed tomography (CT) scan showed the cardiac tumor, which was approximately 40 mm in size, and multiple pulmonary nodules...
February 23, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28220486/cetuximab-plus-irinotecan-versus-panitumumab-in-patients-with-refractory-metastatic-colorectal-cancer-in-ontario-canada
#18
Katarzyna J Jerzak, Scott Berry, Yoo-Joung Ko, Craig Earle, Kelvin K W Chan
The addition of irinotecan to an epidermal growth factor receptor (EGFR) antibody has previously been shown to improve tumor response rate and time to progression but not overall survival (OS) for refractory metastatic colorectal cancer (mCRC). We assessed the "real-world" effectiveness and toxicity of the combination versus monotherapy. In Ontario, Canada, universal public funding is available for either cetuximab plus irinotecan (Cmab + I) combination therapy or panitumumab (Pmab) monotherapy, only in patients with refractory nonmutated RAS mCRC...
May 1, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28199979/atm-mutations-and-e-cadherin-expression-define-sensitivity-to-egfr-targeted-therapy-in-colorectal-cancer
#19
Anna-Lena Geißler, Miriam Geißler, Daniel Kottmann, Lisa Lutz, Christiane D Fichter, Ralph Fritsch, Britta Weddeling, Frank Makowiec, Martin Werner, Silke Lassmann
EGFR-targeted therapy is a key treatment approach in patients with RAS wildtype metastatic colorectal cancers (CRC). Still, also RAS wildtype CRC may be resistant to EGFR-targeted therapy, with few predictive markers available for improved stratification of patients. Here, we investigated response of 7 CRC cell lines (Caco-2, DLD1, HCT116, HT29, LS174T, RKO, SW480) to Cetuximab and correlated this to NGS-based mutation profiles, EGFR promoter methylation and EGFR expression status as well as to E-cadherin expression...
March 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28198009/endoscopic-ultrasound-guided-fine-needle-aspirate-derived-preclinical-pancreatic-cancer-models-reveal-panitumumab-sensitivity-in-kras-wild-type-tumors
#20
William Berry, Elizabeth Algar, Beena Kumar, Christopher Desmond, Michael Swan, Brendan J Jenkins, Daniel Croagh
Pancreatic cancer (PC) is largely refractory to existing therapies used in unselected patient trials, thus emphasizing the pressing need for new approaches for patient selection in personalized medicine. KRAS mutations occur in 90% of PC patients and confer resistance to epidermal growth factor receptor (EGFR) inhibitors (e.g., panitumumab), suggesting that KRAS wild-type PC patients may benefit from targeted panitumumab therapy. Here, we use tumor tissue procured by endoscopic ultrasound-guided fine-needle aspirate (EUS-FNA) to compare the in vivo sensitivity in patient-derived xenografts (PDXs) of KRAS wild-type and mutant PC tumors to panitumumab, and to profile the molecular signature of these tumors in patients with metastatic or localized disease...
February 15, 2017: International Journal of Cancer. Journal International du Cancer
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