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Frontiers in Pharmacology 2020Patients with locally advanced rectal cancer (LARC) are at higher risk of local and distant recurrence and are thus more vulnerable to metastatic diseases. Neoadjuvant...
BACKGROUND
Patients with locally advanced rectal cancer (LARC) are at higher risk of local and distant recurrence and are thus more vulnerable to metastatic diseases. Neoadjuvant chemoradiotherapy (nCRT) and subsequent curative resection with total mesorectal excision (TME) followed by adjuvant chemotherapy have been recommended by the National Comprehensive Cancer Network (NCCN) guidelines as standard of care for LARC patients. However, the efficacy of the addition of epidermal growth factor receptor (EGFR) inhibitors in kirsten rat sarcoma viral oncogene (KRAS)-wild type LARC patients remains uncertain.
MATERIALS
PubMed, Embase, and Web of Science were searched to retrieve records on the application of EGFR inhibitors in a neoadjuvant setting for LARC patients. pCR was used as surrogate endpoint to perform data synthesis in a single-arm setting.
RESULTS
Ten cohorts covering 540 subjects were eligible in this systematic review. The pooled pCR rate for EGFR inhibitors was 15% (95% confidence interval (95% CI), 11-20%; I = 55.2%); the pooled estimates of Grade 3/4 diarrhea, Grade 3/4 hand-foot syndrome, Grade 3/4 acneiform rash were 17% (95% CI, 4-34%; I = 93.3%), 2% (95% CI, 0-5%; I = 13.7%), and 15% (95% CI, 9-22%; I = 65.4%), respectively.
CONCLUSION
The addition of EGFR inhibitors in the nCRT for KRAS-wild type LARC patients provides comparable efficacy and acceptable safety. However, the results should be interpreted cautiously due to the small amount of relevant data and need further confirmation by more future studies.
PubMed: 32499700
DOI: 10.3389/fphar.2020.00706 -
Medicine Mar 2020The efficacy of panitumumab supplementation for colorectal cancer remains controversial. We conduct a systematic review and meta-analysis to explore the influence of... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The efficacy of panitumumab supplementation for colorectal cancer remains controversial. We conduct a systematic review and meta-analysis to explore the influence of panitumumab supplementation on treatment efficacy of colorectal cancer.
METHODS
We search PubMed, EMbase, Web of science, EBSCO, and Cochrane library databases through June 2019 for randomized controlled trials (RCTs) assessing the efficacy of panitumumab supplementation for colorectal cancer. This meta-analysis is performed using the random-effect model.
RESULTS
Five RCTs are included in the meta-analysis. Overall, compared with control group for colorectal cancer, panitumumab supplementation is associated with the increase in objective response for wild-type (WT) KRAS (RR = 1.70; 95% CI = 1.07-2.69; P = .03), but has no remarkable influence on objective response for mutant KRAS (RR = 0.92; 95% CI = 0.79-1.08; P = .32), objective response (RR = 1.35; 95% CI = 1.00-1.83; P = 0.05), progressive disease for WT KRAS (RR = 0.94; 95% CI = 0.85-1.02; P = .15), mortality (RR = 0.86; 95% CI = 0.69-1.08; P = .20), or mortality for WT KRAS (RR = 0.94; 95% CI = 0.84-1.05; P = .28). In addition, grade 3 and 4 adverse events are found to be higher in panitumumab group than those in control group (RR = 1.17; 95% CI = 1.08-1.27; P = .0001; ).
CONCLUSIONS
Panitumumab supplementation can provide some improvement in objective response for colorectal cancer patients with WT KRAS, but results in the increase in grade 3 and 4 adverse events.
Topics: Antineoplastic Agents, Immunological; Antineoplastic Combined Chemotherapy Protocols; Colorectal Neoplasms; Disease-Free Survival; Female; Fluorouracil; Humans; Leucovorin; Male; Organoplatinum Compounds; Panitumumab; Patient Safety; Randomized Controlled Trials as Topic; Survival Analysis; Treatment Outcome
PubMed: 32176047
DOI: 10.1097/MD.0000000000019210 -
In Vivo (Athens, Greece) 2020Despite several clinical trials and advances in understanding the genetic basis of biliary tract cancer (BTC), the addition of epidermal growth factor receptor (EGFR)... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Despite several clinical trials and advances in understanding the genetic basis of biliary tract cancer (BTC), the addition of epidermal growth factor receptor (EGFR) targeted therapy does not seem to enhance the activity of first-line chemotherapy (CHT).
MATERIALS AND METHODS
We carried out a meta-analysis of available randomized clinical trials to assess the efficacy and safety of gemcitabine-based first-line CHT plus monoclonal antibodies against EGFR (EGFR-mAbs) in advanced or metastatic BTC.
RESULTS
In the overall population, the pooled hazard ratio for overall (OS) and progression-free (PFS) survival were 0.82 (95% confidence interval=0.64-1.06) and 0.88 (95% confidence intervaI=0.73-1.08), respectively. No differences were detected in objective response rate between the two groups. Patients treated with gemcitabine-based CHT plus EGFR-mAbs showed a statistically significant increased risk of grade 3-4 neutropenia, grade 3-4 thrombocytopenia and especially grade 3-4 skin rash.
CONCLUSION
The addition of EGFR-mAbs to gemcitabine-based first-line CHT does not significantly improve overall and progression-free survival, nor the objective response rate in patients with advanced BTC and increases the risk of hematological and cutaneous adverse drug events.
Topics: Antibodies, Monoclonal; Antineoplastic Agents, Immunological; Antineoplastic Combined Chemotherapy Protocols; Bile Duct Neoplasms; Clinical Trials, Phase II as Topic; Clinical Trials, Phase III as Topic; ErbB Receptors; Humans; Molecular Targeted Therapy; Neoplasm Staging; Odds Ratio; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 32111744
DOI: 10.21873/invivo.11798 -
Cancer Medicine Sep 2019Systemic cancer therapies may induce infusion reactions (IRs) or hypersensitivities. Metastatic colorectal cancer (mCRC) patients treated with anti-EGFR therapies,... (Meta-Analysis)
Meta-Analysis
The incidence of infusion reactions associated with monoclonal antibody drugs targeting the epidermal growth factor receptor in metastatic colorectal cancer patients: A systematic literature review and meta-analysis of patient and study characteristics.
BACKGROUND
Systemic cancer therapies may induce infusion reactions (IRs) or hypersensitivities. Metastatic colorectal cancer (mCRC) patients treated with anti-EGFR therapies, including cetuximab and panitumumab, may be subject to these reactions. We conducted a meta-analysis to estimate the IR incidence in this population and identify variations in this incidence by patient or study characteristics.
METHODS
A systematic review was conducted to identify observational studies or clinical trials of mCRC patients treated with anti-EGFR therapies that reported occurrences of IRs, hypersensitivity, or allergy/anaphylaxis. The objective of the study was to estimate the incidence of IRs. Random effects models were used to meta-analyze the incidence of IRs overall and stratified by therapy type, study design, geographic location, RAS or KRAS mutation status, grade of reaction severity, and terminology used to describe the reaction.
RESULTS
The pooled estimate for IR incidence was 4.9% (95% confidence interval: 3.6%-6.5%). Lower-grade reactions were more common than higher-grade reactions overall and the incidence of reactions among cetuximab patients was nearly four times that of panitumumab patients (6.1% vs 1.6%).
CONCLUSIONS
IRs occur in approximately 5% of mCRC patients treated with anti-EGFR therapies, and the incidence varies significantly by grade of severity and therapy type. Studies evaluating these outcomes should consider investigating survival outcomes by IR status to determine its prognostic relevance.
Topics: Antibodies, Monoclonal; Cetuximab; Colorectal Neoplasms; Drug Hypersensitivity; ErbB Receptors; Humans; Incidence; Infusions, Intravenous; Observational Studies as Topic; Panitumumab; United States
PubMed: 31376243
DOI: 10.1002/cam4.2413