Abstract:
BACKGROUND:Epidermal growth factor receptor (EGFR) inhibitors prevent cell growth and have shown benefit in the treatment of metastatic colorectal cancer, whether used as single agents or in combination with chemotherapy. Clear benefit has been shown in trials of EGFR monoclonal antibodies (EGFR MAb) but not EGFR tyrosine kinase inhibitors (EGFR TKI). However, there is ongoing debate as to which patient populations gain maximum benefit from EGFR inhibition and where they should be used in the metastatic colorectal cancer treatment paradigm to maximise efficacy and minimise toxicity. OBJECTIVES:To determine the efficacy, safety profile, and potential harms of EGFR inhibitors in the treatment of people with metastatic colorectal cancer when given alone, in combination with chemotherapy, or with other biological agents.The primary outcome of interest was progression-free survival; secondary outcomes included overall survival, tumour response rate, quality of life, and adverse events. SEARCH METHODS:We searched the Cochrane Central Register of Controlled Trials (CENTRAL), the Cochrane Library, Issue 9, 2016; Ovid MEDLINE (from 1950); and Ovid Embase (from 1974) on 9 September 2016; and ClinicalTrials.gov and the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP) on 14 March 2017. We also searched proceedings from the major oncology conferences ESMO, ASCO, and ASCO GI from 2012 to December 2016. We further scanned reference lists from eligible publications and contacted corresponding authors for trials for further information where needed. SELECTION CRITERIA:We included randomised controlled trials on participants with metastatic colorectal cancer comparing: 1) the combination of EGFR MAb and 'standard therapy' (whether chemotherapy or best supportive care) to standard therapy alone, 2) the combination of EGFR TKI and standard therapy to standard therapy alone, 3) the combination of EGFR inhibitor (whether MAb or TKI) and standard therapy to another EGFR inhibitor (or the same inhibitor with a different dosing regimen) and standard therapy, or 4) the combination of EGFR inhibitor (whether MAb or TKI), anti-angiogenic therapy, and standard therapy to anti-angiogenic therapy and standard therapy alone. DATA COLLECTION AND ANALYSIS:We used standard methodological procedures defined by Cochrane. Summary statistics for the endpoints used hazard ratios (HR) with 95% confidence intervals (CI) for overall survival and progression-free survival, and odds ratios (OR) for response rate (RR) and toxicity. Subgroup analyses were performed by Kirsten rat sarcoma viral oncogene homolog (KRAS) and neuroblastoma RAS viral (V-Ras) oncogene homolog (NRAS) status - firstly by status of KRAS exon 2 testing (mutant or wild type) and also by status of extended KRAS/NRAS testing (any mutation present or wild type). MAIN RESULTS:We identified 33 randomised controlled trials for analysis (15,025 participants), including trials of both EGFR MAb and EGFR TKI. Looking across studies, significant risk of bias was present, particularly with regard to the risk of selection bias (15/33 unclear risk, 1/33 high risk), performance bias (9/33 unclear risk, 9/33 high risk), and detection bias (7/33 unclear risk, 11/33 high risk).The addition of EGFR MAb to standard therapy in the KRAS exon 2 wild-type population improves progression-free survival (HR 0.70, 95% CI 0.60 to 0.82; high-quality evidence), overall survival (HR 0.88, 95% CI 0.80 to 0.98; high-quality evidence), and response rate (OR 2.41, 95% CI 1.70 to 3.41; high-quality evidence). We noted evidence of significant statistical heterogeneity in all three of these analyses (progression-free survival: I2 = 76%; overall survival: I2 = 40%; and response rate: I2 = 77%), likely due to pooling of studies investigating EGFR MAb use in different lines of therapy. Rates of overall grade 3 to 4 toxicity, diarrhoea, and rash were increased (moderate-quality evidence for all three outcomes), but there was no evidence for increased rates of neutropenia.For the extended RAS wild-type population (no mutations in KRAS or NRAS), addition of EGFR MAb improved progression-free survival (HR 0.60, 95% CI 0.48 to 0.75; moderate-quality evidence) and overall survival (HR 0.77, 95% CI 0.67 to 0.88; high-quality evidence). Response rate was also improved (OR 4.28, 95% CI 2.61 to 7.03; moderate-quality evidence). We noted significant statistical heterogeneity in the progression-free survival analysis (I2 = 61%), likely due to the pooling of studies combining EGFR MAb with chemotherapy with monotherapy studies.We observed no evidence of a statistically significant difference when EGFR MAb was compared to bevacizumab, in progression-free survival (HR 1.02, 95% CI 0.93 to 1.12; high quality evidence) or overall survival (HR 0.84, 95% CI 0.70 to 1.01; moderate-quality evidence). We noted significant statistical heterogeneity in the overall survival analysis (I2 = 51%), likely due to the pooling of first-line and second-line studies.The addition of EGFR TKI to standard therapy in molecularly unselected participants did not show benefit in limited data sets (meta-analysis not performed). The addition of EGFR MAb to bevacizumab plus chemotherapy in people with KRAS exon 2 wild-type metastatic colorectal cancer did not improve progression-free survival (HR 1.04, 95% CI 0.83 to 1.29; very low quality evidence), overall survival (HR 1.00, 95% CI 0.69 to 1.47; low-quality evidence), or response rate (OR 1.20, 95% CI 0.67 to 2.12; very low-quality evidence) but increased toxicity (OR 2.57, 95% CI 1.45 to 4.57; low-quality evidence). We noted significant between-study heterogeneity in most analyses.Scant information on quality of life was reported in the identified studies. AUTHORS' CONCLUSIONS:The addition of EGFR MAb to either chemotherapy or best supportive care improves progression-free survival (moderate- to high-quality evidence), overall survival (high-quality evidence), and tumour response rate (moderate- to high-quality evidence), but may increase toxicity in people with KRAS exon 2 wild-type or extended RAS wild-type metastatic colorectal cancer (moderate-quality evidence). The addition of EGFR TKI to standard therapy does not improve clinical outcomes. EGFR MAb combined with bevacizumab is of no clinical value (very low-quality evidence). Future studies should focus on optimal sequencing and predictive biomarkers and collect quality of life data.
journal_name
Cochrane Database Syst Revjournal_title
The Cochrane database of systematic reviewsauthors
Chan DLH,Segelov E,Wong RS,Smith A,Herbertson RA,Li BT,Tebbutt N,Price T,Pavlakis Ndoi
10.1002/14651858.CD007047.pub2subject
Has Abstractpub_date
2017-06-27 00:00:00pages
CD007047issn
1469-493Xjournal_volume
6pub_type
杂志文章,meta分析,评审abstract:BACKGROUND:General health checks are common elements of health care in some countries. They aim to detect disease and risk factors for disease with the purpose of reducing morbidity and mortality. Most of the commonly used individual screening tests offered in general health checks have been incompletely studied. Also,...
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abstract:BACKGROUND:Venom immunotherapy (VIT) is commonly used for preventing further allergic reactions to insect stings in people who have had a sting reaction. The efficacy and safety of this treatment has not previously been assessed by a high-quality systematic review. OBJECTIVES:To assess the effects of immunotherapy usi...
journal_title:The Cochrane database of systematic reviews
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doi:10.1002/14651858.CD008838.pub2
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abstract:OBJECTIVES:To estimate the short-term efficacy and toxicity of sulfasalazine for the treatment of rheumatoid arthritis (RA). SEARCH STRATEGY:We searched the Cochrane Musculoskeletal Group trials register, and Medline, up to July 1997, using the search strategy developed by the Cochrane Collaboration (Dickersin 1994). ...
journal_title:The Cochrane database of systematic reviews
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doi:10.1002/14651858.CD000958
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abstract:BACKGROUND:Nursing homes for older people provide an environment likely to promote the acquisition and spread of meticillin-resistant Staphylococcus aureus (MRSA), putting residents at increased risk of colonisation and infection. It is recognised that infection control strategies are important in preventing and contro...
journal_title:The Cochrane database of systematic reviews
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doi:10.1002/14651858.CD006354.pub2
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abstract:BACKGROUND:In general, surgery is believed to offer the best prospects for cure for early stage non-small cell lung cancer (NSCLC). In spite of the intention to consider all patients with stage I-II disease for surgery, there are those who, although technically operable, either refuse surgery or are considered inoperab...
journal_title:The Cochrane database of systematic reviews
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doi:10.1002/14651858.CD002935
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abstract:BACKGROUND:Vitamin A deficiency is a significant public health problem in low and middle income countries. Vitamin A supplementation (VAS) provided to lactating postpartum mothers or to infants less than six months of age are two possible strategies to improve the nutrition of infants at high risk of vitamin A deficien...
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pub_type: 杂志文章,meta分析,评审
doi:10.1002/14651858.CD007480.pub2
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abstract:BACKGROUND:Chronic suppurative otitis media (CSOM), sometimes referred to as chronic otitis media (COM), is a chronic inflammation and infection of the middle ear and mastoid cavity, characterised by ear discharge (otorrhoea) through a perforated tympanic membrane. The predominant symptoms of CSOM are ear discharge and...
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abstract:BACKGROUND:Acute bronchitis leading to ongoing exacerbations is a serious condition predisposed to by viruses, bacteria or environmental factors. It can be fatal. Antibiotic therapy is not particularly useful. An oral Haemophilus influenzae vaccine has been developed. OBJECTIVES:To assess the effects of an oral, monob...
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doi:10.1002/14651858.CD001958.pub2
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abstract:BACKGROUND:Breathlessness is one of the most common symptoms experienced in the advanced stages of malignant and non-malignant disease. Benzodiazepines are widely used for the relief of breathlessness in advanced diseases and are regularly recommended in the literature. However, the evidence for their use for this symp...
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abstract:BACKGROUND:Acute bacterial meningitis remains a disease with high mortality rate, ranging from 10 to 30 percent, despite advances in critical care. It has been estimated that between 5 to 40 percent of all patients can suffer hearing loss. The use of corticosteroids as adjuvant therapy in the treatment of acute bacteri...
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pub_type: 杂志文章,meta分析,评审
doi:10.1002/14651858.CD004305
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abstract:BACKGROUND:Medical professionals routinely carry out surgical hand antisepsis before undertaking invasive procedures to destroy transient micro-organisms and inhibit the growth of resident micro-organisms. Antisepsis may reduce the risk of surgical site infections (SSIs) in patients. OBJECTIVES:To assess the effects o...
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pub_type: 杂志文章,meta分析,评审
doi:10.1002/14651858.CD004288.pub3
更新日期:2016-01-22 00:00:00
abstract:BACKGROUND:Misoprostol (Cytotec, Searle) is a prostaglandin E1 analogue marketed for use in the prevention and treatment of peptic ulcer disease. It is inexpensive, easily stored at room temperature and has few systemic side effects. It is rapidly absorbed orally and vaginally. Although not registered for such use, mis...
journal_title:The Cochrane database of systematic reviews
pub_type: 杂志文章,评审
doi:10.1002/14651858.CD000941
更新日期:2001-01-01 00:00:00
abstract:BACKGROUND:This is one of a series of reviews of methods of cervical ripening and labour induction using standardised methodology. The use of complementary therapies is increasing and some women look to complementary therapies during pregnancy and childbirth to be used alongside conventional medical practice. Acupunctu...
journal_title:The Cochrane database of systematic reviews
pub_type: 杂志文章,meta分析,评审
doi:10.1002/14651858.CD002962.pub3
更新日期:2013-08-15 00:00:00
abstract:BACKGROUND:Overgowns are widely used in newborn nurseries and neonatal intensive care units. It was thought that they may help to prevent the spread of nosocomial infection and serve as a reminder to staff and visitors to wash their hands before contacts with the infant. OBJECTIVES:The objective of this review was to ...
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pub_type: 杂志文章,meta分析,评审
doi:10.1002/14651858.CD003670
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abstract:BACKGROUND:Hysterectomy using an abdominal approach removes either the uterus alone (subtotal hysterectomy) or both the uterus and the cervix (total hysterectomy). The latter is more common but outcomes have not been systematically compared. OBJECTIVES:To assess and compare outcomes with subtotal hysterectomy versus t...
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pub_type: 杂志文章,meta分析,评审
doi:10.1002/14651858.CD004993.pub2
更新日期:2006-04-19 00:00:00
abstract:BACKGROUND:Currently, the two most common surgical techniques for approaching the vas during vasectomy are the incisional method and the no-scalpel technique. Whereas the conventional incisional technique involves the use of a scalpel to make one or two incisions, the no-scalpel technique uses a sharp-pointed, forceps-...
journal_title:The Cochrane database of systematic reviews
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doi:10.1002/14651858.CD004112.pub3
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abstract:BACKGROUND:Gastro-oesophageal reflux (GOR) is an extremely common and usually self-limiting condition in infants. When treatment is required, Cisapride, a pro-kinetic agent, has been commonly prescribed for the symptomatic management of GOR. There have been recent reports of possibly serious adverse events, e.g. an inc...
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doi:10.1002/14651858.CD002300
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journal_title:The Cochrane database of systematic reviews
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abstract:BACKGROUND:Haemophilus influenzae (H. influenzae) is an important cause of meningitis and pneumonia in children. Vaccine cost is a significant barrier to use in low income countries. Determining the size of the effects of the vaccine will enable cost-effectiveness comparisons with competing priorities in low income cou...
journal_title:The Cochrane database of systematic reviews
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journal_title:The Cochrane database of systematic reviews
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abstract:BACKGROUND:Acute sinusitis is a common reason for primary care visits. It causes significant symptoms and often results in time off work and school. OBJECTIVES:We examined whether intranasal corticosteroids (INCS) are effective in relieving symptoms of acute sinusitis. SEARCH STRATEGY:We searched the Cochrane Central...
journal_title:The Cochrane database of systematic reviews
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abstract:BACKGROUND:Previous research suggests that increasing dietary intakes of calcium, potassium or magnesium separately may reduce BP to a small degree over the short term. It is unclear whether increasing intakes of a combination of these minerals produces a larger reduction in BP. OBJECTIVES:To evaluate the effects of c...
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abstract:BACKGROUND:Postoperative nausea and vomiting (PONV) is a common adverse effect of anaesthesia and surgery. Up to 80% of patients may be affected. These outcomes are a major cause of patient dissatisfaction and may lead to prolonged hospital stay and higher costs of care along with more severe complications. Many antiem...
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更新日期:2020-10-19 00:00:00