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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 -
Journal of Managed Care & Specialty... Feb 2019Pharmacogenetic testing can provide predictive insights about the efficacy and safety of drugs used in cancer treatment. Although many drug-gene associations have been...
BACKGROUND
Pharmacogenetic testing can provide predictive insights about the efficacy and safety of drugs used in cancer treatment. Although many drug-gene associations have been reported in the literature, the strength of evidence supporting each association can vary significantly. Even among the subgroup of drugs classified by the PharmGKB database to have a high or moderate level of evidence, there is limited information regarding the economic value of pharmacogenetic testing.
OBJECTIVES
To: (a) summarize the available pharmacoeconomic evidence assessing the value of pharmacogenetic testing for cancer drugs with clinically relevant drug-gene associations; (b) determine the quality of the studies that contain this evidence; and (c) discuss the quality of this evidence with respect to the level of evidence of the drug-gene associations.
METHODS
The PharmGKB database was used to identify cancer drugs with clinically relevant drug-gene associations graded high (1A, 1B) or moderate (2A, 2B). A systematic literature review was conducted using these drugs. Ovid MEDLINE and Embase databases were searched to identify cost-effectiveness, cost-utility, or cost-minimization studies comparing pharmacogenetic testing to an alternative. Cost and effect values from every relevant comparison within the studies were extracted, and the incremental cost-effectiveness ratio (ICER) was either extracted or calculated for each comparison. Quality assessment was conducted for each study using the Quality of Health Economic Studies (QHES) instrument. Qualitative synthesis was used to summarize the data.
RESULTS
The search yielded 2,191 citations, of which 35 studies met the inclusion criteria. Pharmacoeconomic studies were available for the following drugs from the PharmGKB database: fluoropyrimidine, 6-mercaptopurine, irinotecan, carboplatin, cisplatin, erlotinib, gefitinib, cetuximab, panitumumab, and trastuzumab. The studies were conducted in Asia, Europe, Canada, the United States, and Mexico and reported cost-utility, cost-effectiveness, and cost-minimization outcomes. The mean QHES score was 80 (SD = 22) for the studies of drug-gene pairs with high (1A, 1B) and moderate (2A, 2B) levels of evidence (1A = 82, 1B = 93, 2A = 71, and 2B = 74). There was variation across studies in terms of reporting. 109 relevant comparisons were identified within the studies. Of those that reported cost per life-year or cost per quality-adjusted life-year (n = 58 comparisons), pharmacogenetic testing was dominant in 21% overall and 42%, 21%, 17%, and 5% of the comparisons in Asia, Europe, Canada, and the United States, respectively. Variability was observed in the ICER values regardless of geographic region or drug. Pharmacogenetic testing was cost saving in 17 of 19 cost-minimization comparisons and was favored most frequently when compared with genetically indiscriminate strategies containing the drug of interest.
CONCLUSIONS
There was mixed evidence regarding the value of pharmacogenetic testing to guide cancer treatment. For future pharmacogenomic-related economic studies, we recommend prioritizing clinically relevant drug-gene associations and greater adherence to available best practice guidelines for conducting and reporting economic evaluation studies.
DISCLOSURES
No outside funding supported this review. Part of Hussain's research time was supported by a Merit Review Award (I01 BX000545), Medical Research Service, U.S. Department of Veterans Affairs. Hussain also reports personal fees from Bristol-Myers Squibb, AstraZeneca, Novartis, Bayer HealthCare Pharmaceuticals, and France Foundation, outside the submitted work. Onukwugha reports grants from Pfizer and Bayer HealthCare Pharmaceuticals, along with advisory board fees from Novo Nordisk, outside the submitted work. Faruque, Neuberger, and Noh have nothing to disclose.
Topics: Antineoplastic Agents; Cost-Benefit Analysis; Economics, Pharmaceutical; Humans; Neoplasms; Pharmacogenomic Testing; Quality-Adjusted Life Years
PubMed: 30698084
DOI: 10.18553/jmcp.2019.25.2.260 -
BioDrugs : Clinical Immunotherapeutics,... Dec 2018The last decade has seen the increasing use of biological medicines in combination with chemotherapy containing 5-fluorouracil/oxaliplatin or irinotecan for the... (Comparative Study)
Comparative Study Meta-Analysis
Comparative Effectiveness and Safety of Monoclonal Antibodies (Bevacizumab, Cetuximab, and Panitumumab) in Combination with Chemotherapy for Metastatic Colorectal Cancer: A Systematic Review and Meta-Analysis.
BACKGROUND
The last decade has seen the increasing use of biological medicines in combination with chemotherapy containing 5-fluorouracil/oxaliplatin or irinotecan for the treatment of metastatic colorectal cancer (mCRC). These combinations have resulted in increased progression-free survival (PFS) in patients with mCRC; however, there are remaining concerns over the extent of their effect on overall survival (OS). Published studies to date suggest no major differences between the three currently available monoclonal antibodies (MoAbs); however, there are differences in costs. In addition, there is rising litigation in Brazil in order to access these medicines as they are currently not reimbursed.
OBJECTIVE
The aim was to investigate the comparative effectiveness and safety of three MoAbs (bevacizumab, cetuximab and panitumumab) associated with fluoropyrimidine-based chemotherapy regimens and compared to fluoropyrimidine-based chemotherapy alone in patients with mCRC, through an updated systematic review and meta-analysis of concurrent or non-concurrent observational cohort studies, to guide authorities and the judiciary.
METHOD
A systematic review and meta-analysis was performed based on cohort studies published in databases up to November 2017. Effectiveness measures included OS, PFS, post-progression survival (PPS), Response Evaluation Criteria In Solid Tumors (RECIST), response rate, metastasectomy and safety. The methodological quality of the studies was also evaluated.
RESULTS
A total of 21 observational cohort studies were included. There were statistically significant and clinically relevant benefits in patients treated with bevacizumab versus no bevacizumab mainly around OS, PFS, PPS and the metastasectomy rate, but not for the disease control rates. However, there was an increase in treatment-related toxicities and concerns with the heterogeneity of the studies.
CONCLUSION
The results pointed to an advantage in favor of bevacizumab for OS, PFS, PPS, and metastasectomy. Although this advantage may be considered clinically modest, bevacizumab represents a hope for increased survival and a chance of metastasectomy for patients with mCRC. However, there are serious adverse events associated with its use, especially severe hypertension and gastrointestinal perforation, that need to be considered.
Topics: Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Brazil; Cetuximab; Colorectal Neoplasms; Cost-Benefit Analysis; Disease-Free Survival; Fees, Pharmaceutical; Fluorouracil; Humans; Hypertension; Incidence; Intestinal Perforation; Irinotecan; Oxaliplatin; Panitumumab; Reimbursement Mechanisms; Response Evaluation Criteria in Solid Tumors
PubMed: 30499082
DOI: 10.1007/s40259-018-0322-1 -
Clinical Colorectal Cancer Jun 2018Monoclonal antibody inhibitors of the epidermal growth factor receptor (EGFR) have been shown to improve outcomes for patients with metastatic colorectal cancer (mCRC)...
Monoclonal antibody inhibitors of the epidermal growth factor receptor (EGFR) have been shown to improve outcomes for patients with metastatic colorectal cancer (mCRC) without RAS gene mutations. However, treatment with anti-EGFR agents can be associated with toxicities of the skin, nails, hair, and eyes. Because these dermatologic toxicities can result in treatment discontinuation and affect patient quality of life, their management is an important focus when administering anti-EGFR monoclonal antibodies. The present systematic review describes the current data reporting the nature and incidence of, and management and treatment options for, dermatologic toxicities occurring during anti-EGFR treatment of mCRC. A search of the National Library of Medicine PubMed database from January 1, 2009, to August 18, 2016, identified relevant reports discussing dermatologic toxicity management among patients with mCRC receiving anti-EGFR therapy. The studies were grouped by type and rated by level of evidence using the GRADE approach developed by the Agency for Healthcare Research and Quality. Overall, 269 reports were reviewed (nonrandomized trials, n = 120; randomized trials, n = 31; retrospective studies, n = 15; reviews, n = 39). Dermatologic toxicity of any grade occurs in most patients who receive anti-EGFR therapy; approximately 10% to 20% of patients experienced grade 3/4 toxicity. The most common dermatologic toxicities include papulopustular/acneiform rash, xerosis, and pruritus; however, nail changes, hair abnormalities, and ocular conditions also occur. Guidance for managing these toxicities includes the use of inexpensive emollient ointments and moisturizers, avoidance of sun exposure, avoidance of irritants, and the use of short showers. Several studies also found that preemptive treatment was more effective than reactive treatment at limiting the incidence and severity of skin toxicity. With appropriate treatment, the dermatologic toxicities associated with anti-EGFR monoclonal antibody therapy can be managed, minimizing patient discomfort and the need for therapy interruption and/or discontinuation. Additionally, preemptive treatment can reduce dermatologic toxicity severity, ultimately yielding better quality of life.
Topics: Antibodies, Monoclonal; Antineoplastic Agents, Immunological; Cetuximab; Colorectal Neoplasms; Drug Eruptions; ErbB Receptors; Humans; Incidence; Panitumumab
PubMed: 29576427
DOI: 10.1016/j.clcc.2017.12.004 -
Scientific Reports Feb 2018Hypomagnesemia is a recognized side-effect of cetuximab- or panitumumab-based chemotherapy for metastatic colorectal cancer (mCRC). The clinical relevance of... (Meta-Analysis)
Meta-Analysis Review
Hypomagnesemia is a recognized side-effect of cetuximab- or panitumumab-based chemotherapy for metastatic colorectal cancer (mCRC). The clinical relevance of hypomagnesemia is under debate. Thus, a systematic review and meta-analysis of retrospective studies and randomized clinical trials (RCTs) comparing hypomagnesemia with normal magnesium levels in wild-type KRAS mCRC was performed. One RCT, two retrospective studies, and two American Society of Clinical Oncology (ASCO) and European Society for Medical Oncology (ESMO) conference presentations from phase III RCTs involving 1723 patients were included in this study. Patients with hypomagnesemia demonstrated better progression-free survival (PFS) (Hazard ratio [HR]: 0.64; 95% confidence interval [CI]: 0.47-0.88), overall survival (OS) (HR: 0.72; 95% CI: 0.53-0.92), and objective response rate (ORR) (Risk ratio [RR]: 1.81; 95% confidence interval [CI]: 1.30-2.52). By subgroup analysis, frontline, later lines or combination therapy with hypomagnesemia were associated with PFS benefits (HR: 0.78; 95% CI: 0.62-0.98; HR: 0.60; 95% CI: 0.40-0.90; HR: 0.62; 95% CI: 0.41-0.94, respectively). In patients with wild-type KRAS mCRC, hypomagnesemia is associated with better clinical benefits of PFS, OS and ORR when treated with cetuximab- or panitumumab-based chemotherapy. Future clinical trials should corroborate its predictive role.
Topics: Antibodies, Monoclonal; Antineoplastic Agents, Immunological; Cetuximab; Colorectal Neoplasms; Humans; Magnesium; Neoplasm Metastasis; Panitumumab; Proto-Oncogene Proteins p21(ras); Randomized Controlled Trials as Topic; Survival Analysis
PubMed: 29391418
DOI: 10.1038/s41598-018-19835-8 -
Health Technology Assessment... Jun 2017Colorectal cancer is the fourth most commonly diagnosed cancer in the UK after breast, lung and prostate cancer. People with metastatic disease who are sufficiently fit... (Review)
Review
The clinical effectiveness and cost-effectiveness of cetuximab (review of technology appraisal no. 176) and panitumumab (partial review of technology appraisal no. 240) for previously untreated metastatic colorectal cancer: a systematic review and economic evaluation.
BACKGROUND
Colorectal cancer is the fourth most commonly diagnosed cancer in the UK after breast, lung and prostate cancer. People with metastatic disease who are sufficiently fit are usually treated with active chemotherapy as first- or second-line therapy. Targeted agents are available, including the antiepidermal growth factor receptor (EGFR) agents cetuximab (Erbitux, Merck Serono UK Ltd, Feltham, UK) and panitumumab (Vecitibix, Amgen UK Ltd, Cambridge, UK).
OBJECTIVE
To investigate the clinical effectiveness and cost-effectiveness of panitumumab in combination with chemotherapy and cetuximab in combination with chemotherapy for rat sarcoma () wild-type (WT) patients for the first-line treatment of metastatic colorectal cancer.
DATA SOURCES
The assessment included a systematic review of clinical effectiveness and cost-effectiveness studies, a review and critique of manufacturer submissions, and a de novo cohort-based economic analysis. For the assessment of effectiveness, a literature search was conducted up to 27 April 2015 in a range of electronic databases, including MEDLINE, EMBASE and The Cochrane Library.
REVIEW METHODS
Studies were included if they were randomised controlled trials (RCTs) or systematic reviews of RCTs of cetuximab or panitumumab in participants with previously untreated metastatic colorectal cancer with WT status. All steps in the review were performed by one reviewer and checked independently by a second. Narrative synthesis and network meta-analyses (NMAs) were conducted for outcomes of interest. An economic model was developed focusing on first-line treatment and using a 30-year time horizon to capture costs and benefits. Costs and benefits were discounted at 3.5% per annum. Scenario analyses and probabilistic and univariate deterministic sensitivity analyses were performed.
RESULTS
The searches identified 2811 titles and abstracts, of which five clinical trials were included. Additional data from these trials were provided by the manufacturers. No data were available for panitumumab plus irinotecan-based chemotherapy (folinic acid + 5-fluorouracil + irinotecan) (FOLFIRI) in previously untreated patients. Studies reported results for WT subgroups. First-line treatment with anti-EGFR therapies in combination with chemotherapy appeared to have statistically significant benefits for patients who are WT. For the independent economic evaluation, the base-case incremental cost-effectiveness ratio (ICER) for WT patients for cetuximab plus oxaliplatin-based chemotherapy (folinic acid + 5-fluorouracil + oxaliplatin) (FOLFOX) compared with FOLFOX was £104,205 per quality-adjusted life-year (QALY) gained; for panitumumab plus FOLFOX compared with FOLFOX was £204,103 per QALY gained; and for cetuximab plus FOLFIRI compared with FOLFIRI was £122,554 per QALY gained. The ICERs were sensitive to treatment duration, progression-free survival, overall survival (resected patients only) and resection rates.
LIMITATIONS
The trials included WT populations only as subgroups. No evidence was available for panitumumab plus FOLFIRI. Two networks were used for the NMA and model, based on the different chemotherapies (FOLFOX and FOLFIRI), as insufficient evidence was available to the assessment group to connect these networks.
CONCLUSIONS
Although cetuximab and panitumumab in combination with chemotherapy appear to be clinically beneficial for WT patients compared with chemotherapy alone, they are likely to represent poor value for money when judged by cost-effectiveness criteria currently used in the UK. It would be useful to conduct a RCT in patients with WT.
STUDY REGISTRATION
This study is registered as PROSPERO CRD42015016111.
FUNDING
The National Institute for Health Research Health Technology Assessment programme.
Topics: Antibodies, Monoclonal; Antineoplastic Agents; Antineoplastic Agents, Immunological; Cetuximab; Colorectal Neoplasms; Cost-Benefit Analysis; Female; Humans; Male; Neoplasm Metastasis; Panitumumab; Technology Assessment, Biomedical; Treatment Outcome
PubMed: 28682222
DOI: 10.3310/hta21380 -
Cancer Treatment Reviews Feb 2017Both stereotactic radiotherapy (SRT) and immune- or targeted therapy play an increasingly important role in personalized treatment of metastatic disease. Concurrent... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND AND PURPOSE
Both stereotactic radiotherapy (SRT) and immune- or targeted therapy play an increasingly important role in personalized treatment of metastatic disease. Concurrent application of both therapies is rapidly expanding in daily clinical practice. In this systematic review we summarize severe toxicity observed after concurrent treatment.
MATERIAL AND METHODS
PubMed and EMBASE databases were searched for English literature published up to April 2016 using keywords "radiosurgery", "local ablative therapy", "gamma knife" and "stereotactic", combined with "bevacizumab", "cetuximab", "crizotinib", "erlotinib", "gefitinib", "ipilimumab", "lapatinib", "sorafenib", "sunitinib", "trastuzumab", "vemurafenib", "PLX4032", "panitumumab", "nivolumab", "pembrolizumab", "alectinib", "ceritinib", "dabrafenib", "trametinib", "BRAF", "TKI", "MEK", "PD1", "EGFR", "CTLA-4" or "ALK". Studies performing SRT during or within 30days of targeted/immunotherapy, reporting severe (⩾Grade 3) toxicity were included.
RESULTS
Concurrent treatment is mostly well tolerated in cranial SRT, but high rates of severe toxicity were observed for the combination with BRAF-inhibitors. The relatively scarce literature on extra-cranial SRT shows a potential risk of increased toxicity when SRT is combined with EGFR-targeting tyrosine kinase inhibitors and bevacizumab, which was not observed for cranial SRT.
CONCLUSIONS
This review gives a best-possible overview of current knowledge and its limitations and underlines the need for a timely generation of stronger evidence in this rapidly expanding field.
Topics: Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; CTLA-4 Antigen; Cetuximab; Humans; Immunotherapy; Molecular Targeted Therapy; Neoplasms; Niacinamide; Phenylurea Compounds; Radiosurgery; Sorafenib
PubMed: 28056412
DOI: 10.1016/j.ctrv.2016.11.013