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Medicine International 2024The present systematic review evaluated the effectiveness of anti-EGFR therapy in combination with radiotherapy (RT) or with chemoradiation compared with the existing...
The present systematic review evaluated the effectiveness of anti-EGFR therapy in combination with radiotherapy (RT) or with chemoradiation compared with the existing standard of care for the treatment of locally advanced head and neck squamous cell carcinoma (LAHNSCC). The PubMed, SCOPUS, EMBASE and COCHRANE databases were searched and 12 phase III randomized controlled trials were included. The effectiveness of the anti-EGFR monoclonal antibody cetuximab was evaluated in nine trials. Nimotuzumab (one trial), zalutumumab (one trial) and panitumumab (one trial) were the monoclonal antibodies evaluated in the remaining three trials. One study tested the effectiveness of adding cetuximab to radical RT and found that patients with LAHNSCC exhibited improvement in locoregional control (LRC), overall survival (OS) and progression-free survival (PFS) compared with those of patients treated with RT alone. A total of three studies tested the effectiveness of adding an anti-EGFR agent to chemoradiation. Of these, a single institution study in which patients received cisplatin at 30 mg/m weekly, instead of the standard doses of 100 mg/m every 3 weeks or 40 mg/m every week, reported significant improvement in PFS with the addition of nimotuzumab to chemoradiotherapy without an improvement in overall survival. However, the other two studies indicated that, when added to standard chemoradiation, the anti-EGFR monoclonal antibodies cetuximab or zalutumumab did not improve survival outcomes. Two phase III trials evaluated RT plus an anti-EGFR agent compared with chemoradiation alone. Of these, one study reported inferior outcomes with cetuximab-RT in terms of OS and LRC, whereas the other study with panitumumab plus RT failed to prove the non-inferiority. Two trials evaluated induction chemotherapy followed by cetuximab-RT compared with chemoradiotherapy and reported no benefits in terms of OS or PFS. Furthermore, one study evaluated induction chemotherapy followed by cetuximab-RT compared with induction chemotherapy followed by chemoradiotherapy and found no improvement in OS or PFS. Finally, three phase III trials tested the effectiveness of cetuximab plus RT in the treatment of human papillomavirus-positive oropharyngeal carcinoma, and found it to be inferior compared with cisplatin-RT in terms of OS, PFS and failure-free survival. Based on the aforementioned findings, it is difficult to conclude that anti-EGFR therapy in any form has an advantage over conventional chemoradiation in the treatment of LAHNSCC.
PubMed: 38873325
DOI: 10.3892/mi.2024.165 -
Diseases (Basel, Switzerland) Apr 2024This systematic review critically evaluates the impact of systemic treatments on outcomes and quality of life (QoL) in patients with RAS-positive stage IV colorectal... (Review)
Review
This systematic review critically evaluates the impact of systemic treatments on outcomes and quality of life (QoL) in patients with RAS-positive stage IV colorectal cancer, with studies published up to December 2023 across PubMed, Scopus, and Web of Science. From an initial pool of 1345 articles, 11 relevant studies were selected for inclusion, encompassing a diverse range of systemic treatments, including panitumumab combined with FOLFOX4 and FOLFIRI, irinotecan paired with panitumumab, regorafenib followed by cetuximab ± irinotecan and vice versa, and panitumumab as a maintenance therapy post-induction. Patient demographics predominantly included middle-aged to elderly individuals, with a slight male predominance. Racial composition, where reported, showed a majority of Caucasian participants, highlighting the need for broader demographic inclusivity in future research. Key findings revealed that the addition of panitumumab to chemotherapy (FOLFOX4 or FOLFIRI) did not significantly compromise QoL while notably improving disease-free survival, with baseline EQ-5D HSI mean scores ranging from 0.76 to 0.78 and VAS mean scores from 70.1 to 74.1. Improvements in FACT-C scores and EQ-5D Index scores particularly favored panitumumab plus best supportive care in KRAS wild-type mCRC, with early dropout rates of 38-42% for panitumumab + BSC. Notably, cetuximab + FOLFIRI was associated with a median survival of 25.7 months versus 16.4 months for FOLFIRI alone, emphasizing the potential benefits of integrating targeted therapies with chemotherapy. In conclusion, the review underscores the significant impact of systemic treatments, particularly targeted therapies and their combinations with chemotherapy, on survival outcomes and QoL in patients with RAS-positive stage IV colorectal cancer, and the need for personalized treatment.
PubMed: 38667537
DOI: 10.3390/diseases12040079 -
BMC Gastroenterology Feb 2024To evaluate the benefit of bevacizumab under the comprehensive treatment strategy and its advantages over other drugs, so as to provide reference for the formulation of... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To evaluate the benefit of bevacizumab under the comprehensive treatment strategy and its advantages over other drugs, so as to provide reference for the formulation of clinical plans.
METHODS
As of October 1, 2022, the randomized controlled clinical trials of bevacizumab in combination with metastatic colorectal cancer published in PubMed, Cochrane Library and Medline databases were searched. The odds ratio (OR) and its 95% confidence interval (CI) were used to evaluate the short-term disease control effect and long-term survival of the treatment strategy.
RESULTS
21 RCTs (6665 patients; 3356 patients in the experimental group and 3309 patients in the control group; average age, 55-75 years) were treated with bevacizumab as the experimental group for metastatic colorectal cancer. BEV has stronger anti-tumor activity than the single treatment scheme (OR = 1.30, 95% CI: 1.11-1.52). And Benefits of the BEV group were 0.73 (0.55, 0.96), 1.26 (0.71, 2.24), 1.63 (0.92, 2.87) and 0.07 (0.02, 0.25) compared with CET, VAN, CED and PAN respectively. The disease control of BEV combined therapy was better (OR = 1.36, 95% CI: 1.04-1.78). The same as compared with cediranib (OR = 1.94, 95% CI: 1.06-3.55). However, the long-term prognosis of BEV, including the overall survival (HRs = 0.98, 95% CI: 0.84-1.15) and progression-free survival (HRs = 1.05,95% CI: 0.97-1.13) were not prolonged. The survival benefits of cetuximab and panitumumab were not reflected.
CONCLUSION
The addition of BEV can enhance the anti-tumor ability and disease control, while cetuximab and panitumumab may have stronger ability. However, it did not effectively improve the survival of patients. A more reasonable and effective treatment plan needs more clinical experimental support.
Topics: Humans; Middle Aged; Aged; Bevacizumab; Cetuximab; Panitumumab; Colorectal Neoplasms; Colonic Neoplasms; Rectal Neoplasms; Antineoplastic Combined Chemotherapy Protocols
PubMed: 38302922
DOI: 10.1186/s12876-024-03134-w -
Critical Reviews in Oncology/hematology Nov 2023In RAS wild type (wt) metastatic colorectal cancer (mCRC) maintenance therapy after induction with fluoropyrimidine (FP)-based cytotoxic therapy (CT) plus anti-EGFR... (Review)
Review
BACKGROUND
In RAS wild type (wt) metastatic colorectal cancer (mCRC) maintenance therapy after induction with fluoropyrimidine (FP)-based cytotoxic therapy (CT) plus anti-EGFR agents is controversial.
METHODS
Phase II-III randomized trials were included. Maintenance strategies considered were: observation, anti-EGFR or FP monotherapy, FP + anti-EGFR, doublet CT + anti-EGFR.
RESULTS
Maintenance with FP + anti-EGFR (HR 0.56, 95% CrI 0.36-0.89) showed the greatest PFS benefit compared to observation, ranking first on SUCRA analysis (96.4%). Considering OS, doublet CT+ anti-EGFR, FP + anti-EGFR and anti-EGFR monotherapy yielded similar results. For PFS, FP + anti-EGFR confirmed to be valuable in BRAF wt patients and left sided tumors. In left sided tumors, the OS benefit of adding CT was limited. FP plus anti-EGFR showed a favourable safety profile compared to doublet CT + anti-EGFR.
CONCLUSIONS
FP + anti-EGFR can be considered a valuable maintenance option in RAS wt mCRC. EGFR monotherapy can be considered, especially in left-sided tumors.
PubMed: 37659764
DOI: 10.1016/j.critrevonc.2023.104106 -
The Oncologist Oct 2023HER2 overexpression/amplification in patients with RAS wild-type (WT) metastatic colorectal cancer (mCRC) may be associated with resistance to standard-of-care anti-EGFR... (Meta-Analysis)
Meta-Analysis
BACKGROUND
HER2 overexpression/amplification in patients with RAS wild-type (WT) metastatic colorectal cancer (mCRC) may be associated with resistance to standard-of-care anti-EGFR therapies. Given the lack of comprehensive investigations into this association, we assessed the prognostic or predictive effect of HER2 amplification/overexpression on anti-EGFR treatment outcomes.
METHODS
A systematic review of MEDLINE, Embase, and Cochrane Library (2001-2021) identified studies evaluating progression-free survival (PFS), overall response rate (ORR), and overall survival (OS) in HER2-positive vs. HER2-negative patients with RAS WT mCRC who received anti-EGFR treatments and whose HER2 status was known. Meta-analyses of proportions (ORR) and hazard ratios (PFS, OS) were performed using random-effect models with pre-specified sensitivity analyses.
RESULTS
Five high-quality retrospective cohort studies were included in the meta-analyses representing 594 patients with mCRC. All patients received anti-EGFR treatment, either as monotherapy or in combination with chemotherapy. Meta-analysis of PFS demonstrated a 2.84-fold higher risk of death or progression (95% CI, 1.44-5.60) in patients with HER2-positive (vs. HER2-negative) RAS WT mCRC treated with anti-EGFR regimens. The odds of response to anti-EGFR treatment were 2-fold higher in HER2-negative vs. HER2-positive (odds ratio, 1.96 [95% CI, 1.10-3.48]). Differences in OS were not statistically significant. Sensitivity analyses confirmed the robustness of the base-case estimates.
CONCLUSIONS
While this study could not account for all confounding factors, in patients with RAS WT mCRC who received anti-EGFR therapy, HER2 overexpression/amplification was associated with worse PFS and ORR and may therefore predict poorer outcomes. HER2 testing is important to inform treatment decisions and could optimize outcomes for patients.
Topics: Humans; Antibodies, Monoclonal; Colorectal Neoplasms; Retrospective Studies; ErbB Receptors; Panitumumab; Colonic Neoplasms; Rectal Neoplasms; Proto-Oncogene Proteins p21(ras); Antineoplastic Combined Chemotherapy Protocols
PubMed: 37463037
DOI: 10.1093/oncolo/oyad200 -
World Journal of Surgical Oncology Aug 2022To date, the optimal treatment for potentially resectable metastatic colorectal cancer (mCRC) patients has yet to be determined. Encouraging results have been reported... (Meta-Analysis)
Meta-Analysis
BACKGROUND
To date, the optimal treatment for potentially resectable metastatic colorectal cancer (mCRC) patients has yet to be determined. Encouraging results have been reported in studies exploring the efficacy of triplet chemotherapy plus anti-epidermal growth factor receptor (anti-EGFR) target agents. Thus, we conducted a meta-analysis to evaluate the efficacy and safety of triplet chemotherapy plus anti-EGFR target agents.
METHODS
We systematically searched the PubMed, Embase, and Web of Science databases from December 2004 to October 2021 for studies examining the efficacy of triplet chemotherapy plus anti-EGFR target agents in mCRC patients. The primary outcomes were the objective response rate (ORR) and R0 resection rate (R0RR), and the secondary outcomes were median progression-free survival (mPFS), median overall survival (mOS), and toxicity. Data were analyzed with R software 4.1.2.
RESULTS
Fourteen studies comprising 762 patients with mCRC were included in this meta-analysis. Analysis with a random effects model revealed that after treatment with triplet chemotherapy plus anti-EGFR target agents, the pooled ORR was 82% (95% CI= 76-88%, I= 76%), and the pooled R0RR of colorectal liver metastasis (CLM) was 59% (95% CI= 49-68%, I= 60%). The mPFS ranged from 9.5 to 17.8 months, and the mOS ranged from 24.7 to 62.5 months. A total of 648 grade 3 or 4 adverse events were reported; the most commonly reported events were diarrhea (174/648), neutropenia (157/648), and skin toxicity (95/648), which had pooled prevalence rates of 29% (95% CI= 20-39%, I= 84%), 28% (95% CI= 20-37%, I= 77%), and 17% (95% CI= 11-24%, I= 66%), respectively.
CONCLUSIONS
Triplet chemotherapy plus anti-EGFR agents therapy seems to be capable of increasing the ORR of mCRC patients and the R0RR of CLM patients. The toxicity of this treatment is manageable. High-quality randomized controlled trial (RCT) studies are required for further validation.
Topics: Antineoplastic Combined Chemotherapy Protocols; Colonic Neoplasms; Colorectal Neoplasms; Humans; Panitumumab; Rectal Neoplasms
PubMed: 35965307
DOI: 10.1186/s12957-022-02707-x -
International Journal of Environmental... Jul 2022Despite substantially elevated risk of serious adverse events (SAEs) from targeted therapy in combination with chemotherapy, comprehensive pharmacovigilance research is... (Meta-Analysis)
Meta-Analysis
Safety Assessment on Serious Adverse Events of Targeted Therapeutic Agents Prescribed for RAS Wild-Type Metastatic Colorectal Cancer: Systematic Review and Network Meta-Analysis.
Despite substantially elevated risk of serious adverse events (SAEs) from targeted therapy in combination with chemotherapy, comprehensive pharmacovigilance research is limited. This study aims to systematically assess SAE risks of commonly prescribed targeted agents (bevacizumab, cetuximab, and panitumumab) in patients with rat sarcoma viral oncogene homolog (RAS) wild-type metastatic colon cancer. Keyword searches of Cochrane Library, Clinical Key and MEDLINE were conducted per PRISMA-NMA guidelines. Frequentist network meta-analysis was performed with eight randomized controlled trials to compare relative risk (RR) of 21 SAE profiles. The risks of hematological, gastrointestinal, neurological SAE were insignificant among targeted agents (p > 0.05). The risk of serious hypertension was substantially elevated in bevacizumab-based chemotherapy (p < 0.05), whereas panitumumab-based chemotherapy had markedly elevated risk of serious thromboembolism (RR 3.65; 95% CI 1.30−10.26). Although both cetuximab and panitumumab demonstrated increased risk of serious dermatological and renal toxicities, panitumumab-based chemotherapy has relatively higher risk of skin toxicity (RR 15.22; 95% CI 7.17−32.35), mucositis (RR 3.18; 95% CI 1.52−6.65), hypomagnesemia (RR 20.10; 95% CI 5.92−68.21), and dehydration (RR 2.81; 95% CI 1.03−7.67) than cetuximab-based chemotherapy. Thus, further studies on risk stratification and SAE management are warranted for safe administration of targeted agents.
Topics: Antineoplastic Agents; Bevacizumab; Cetuximab; Colorectal Neoplasms; Humans; Network Meta-Analysis; Panitumumab
PubMed: 35954563
DOI: 10.3390/ijerph19159196 -
Frontiers in Oncology 2021Systemic treatments, namely, either monotherapy or combination therapy, are commonly administered to patients with advanced or metastatic colorectal cancer (CRC). This...
BACKGROUND
Systemic treatments, namely, either monotherapy or combination therapy, are commonly administered to patients with advanced or metastatic colorectal cancer (CRC). This study aimed to provide the complete efficacy and safety profiles and ranking of systemic therapies for the treatment of unresectable advanced or metastatic CRC.
METHODS
We searched PubMed, Embase, the Cochrane Library, and ClinicalTrials.gov from inception until June 30, 2021, and also the bibliographies of relevant studies. Randomized controlled trials comparing two or more treatments, namely, at least capecitabine, 5-fluorouracil, leucovorin, irinotecan, bevacizumab, cetuximab, oxaliplatin, or panitumumab were investigated. A network meta-analysis using the Bayesian approach was performed to compare the efficacy and safety of treatments. The surface under the cumulative ranking curve (SUCRA) was calculated for the probability of each treatment as the most effective. The overall response rate (ORR), disease control rate (DCR), overall survival (OS), progression-free survival (PFS), adverse events (AEs) grade ≥3, and serious adverse events (SAEs) were evaluated.
RESULTS
One hundred two publications with 36,147 participants were assigned to 39 different treatments. Among 11 treatments with full information on six outcomes, FOLFIRI/FOLFOX/FOLFOXIRI + bevacizumab significantly improved both the ORR and DCR, compared to FOLFIRI. Although FOLFOX and FOLFIRI/FOLFOX + cetuximab significantly prolonged both OS and PFS, treatments were comparable in terms of AEs grade ≥3 and SAEs. The top highest SUCRA values were observed in the FOLFOXIRI + panitumumab group for ORR (96%) and DCR (99%), FOLFIRI + bevacizumab + panitumumab group for OS (62%) and PFS (54%), and FOLFOXIRI + bevacizumab group for AEs grade ≥3 (59%) and SAEs (59%) outcomes.
CONCLUSIONS
These findings suggest an available range of systemic treatment therapies with different efficacy and safety profiles with patients. Further investigations of the side effects and mutation status are required to confirm our findings.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/, identifier CRD42019127772.
PubMed: 35223449
DOI: 10.3389/fonc.2021.756214 -
Medicine Jul 2020Test on the KRAS somatic mutation status is necessary before cetuximab and panitumumab treatments are given to colorectal cancer patients. Metastatic colorectal cancer... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Test on the KRAS somatic mutation status is necessary before cetuximab and panitumumab treatments are given to colorectal cancer patients. Metastatic colorectal cancer patients sometimes lack tumor tissue samples, and the testing of KRAS mutation in plasma samples requires highly sensitive methods.
OBJECTIVES
The aim of this study was to evaluate the accuracy of digital PCR in detecting KRAS mutation in plasma samples of colorectal cancer patients.
DATA SOURCES
Literature research was conducted in Pubmed, Embase, and Cochrane Library.
STUDY ELIGIBILITY CRITERIA, PARTICIPANTS, AND INTERVENTIONS
Database searching found 188 relevant studies. After removing duplicates, eligible studies were selected from 151 publications using the following exclusion criteria: STUDY APPRAISAL AND SYNTHESIS METHODS:: Data were extracted from the eligible studies by 2 independent researchers. Pooled accuracy parameters were calculated from those extracted data using Meta-DiSc and STATA software.
RESULTS
Twelve eligible studies were selected for the systematic review and meta-analysis. After calculation, the pooled sensitivity and specificity were 0.83 (95% CI: 0.79-0.86) and 0.91 (95%CI: 0.88-0.93), respectively. Pooled positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio were 7.30 (95%CI: 4.78-11.17), 0.22 (95%CI: 0.15-0.32), and 41.00 (95%CI: 21.07-79.78), respectively. Area under curve of the summarized ROC curve was 0.9322.
LIMITATIONS
Although no significant bias was identified, number of included studies was still quite small, especially in subgroup analysis.
CONCLUSIONS AND IMPLICATION OF KEY FINDINGS
Digital PCR showed high accuracy and could be a reliable detection method for KRAS mutation in plasma samples. Large-cohort prospective study is required to further confirm the usefulness of digital PCR in KRAS mutation detection.
Topics: Adult; Aged; Colorectal Neoplasms; Female; Humans; Male; Middle Aged; Mutation; Polymerase Chain Reaction; Proto-Oncogene Proteins p21(ras); ROC Curve; Reproducibility of Results; Sensitivity and Specificity
PubMed: 32664155
DOI: 10.1097/MD.0000000000021171 -
Critical Reviews in Oncology/hematology Sep 2020The most effective regimen is unclear for patients with recurrent or metastatic head and neck squamous cell carcinomas (R/M HNSCC). We performed a systematic review and... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The most effective regimen is unclear for patients with recurrent or metastatic head and neck squamous cell carcinomas (R/M HNSCC). We performed a systematic review and meta-analysis of randomized controlled trials (RCTs) investigating only systemic therapy for R/M HNSCC.
METHODS
This systematic review followed PRISMA and the Cochrane Collaboration Handbook for Systematic Reviews of Interventions. Endpoints included overall survival (OS), progression-free survival (PFS) and overall response rates (ORR).
RESULTS
55 RCTs from 1990-November 2019 qualified for review (n=12132). Only PD-1/PDL-1 inhibitors increased OS in R/M HNSCC platinum-resistant disease against their control (HR = 0·79, 95%CI 0·70-0.90, p<0·001), especially for PD-L1 ≥ 1% expressing tumours (HR = 0·72, 95%CI 0·60-0·86, p<0·001). PFS was prolonged for anti-EGFR agents against methotrexate when used in a second line setting (HR = 0·74, 95 %CI 0·62-0·87, p=0·001), and when cetuximab (HR = 0·60, 95%CI 0·49-0·72, p<0·0001) and panitumumab (HR = 0·76, 95%CI 0·65-0·89, p=0·001) were introduced to platinum-based regimens for first-line treatment.
CONCLUSIONS
PD-1/PD-L1 inhibitors may represent the future of R/M HNSCC treatment. However, EGFR inhibitors may still play improve clinical outcomes.
Topics: Antineoplastic Combined Chemotherapy Protocols; Cetuximab; Head and Neck Neoplasms; Humans; Methotrexate; Neoplasm Recurrence, Local; Squamous Cell Carcinoma of Head and Neck
PubMed: 32569853
DOI: 10.1016/j.critrevonc.2020.102984