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World Journal of Surgical Oncology Nov 2023The meta-analysis aimed to assess the clinical efficacy of chemotherapeutic triplet-drug regimen combined with anti-EGFR antibody in patients with initially unresectable... (Meta-Analysis)
Meta-Analysis
The meta-analysis aimed to assess the clinical efficacy of chemotherapeutic triplet-drug regimen combined with anti-EGFR antibody in patients with initially unresectable metastatic colorectal cancer (mCRC). A systematic literature search was performed in PubMed Publisher. Studies evaluating FOLFOXIRI combine with panitumumab or cetuximab as the therapy for initially unresectable mCRC were included. The primary outcome was objective response rate (ORR) and rate of R0 resections. The secondary outcomes included overall survival (OS), progression-free survival (PFS), and grades 3 or 4 adverse events. R software (version 4.0.2) and RevMan (version 5.3) were used to analyze the extracted data. The studies included were published between 2010 and 2021, involving four single-arm phase II trials and two randomized phase II trials. A total of 6 studies with 282 patients were included. The data showed a significant benefit for the FOLFOXIRI + anti-EGFR antibody arm compared with FOLFOXIRI arm (RR 1.33; 95% CI, 1.13-1.58; I = 0%, P < 0.05). The pooled ORR and pooled rate of R0 resection in patients who receiving FOLFOXIRI + anti-EGFR antibody were 85% (95% CI, 0.78-0.91; I = 58%) and 42% (95% CI, 0.32-0.53; I = 62%), respectively. The range of median PFS between all the six studies was 9.5-15.5 months, with weighted pooled median PFS mean 11.7 months. The range of median OS between all the four studies was 24.7-37 months, with weighted pooled median PFS mean 31.9 months. The common grades 3 and 4 adverse events were diarrhea and neutropenia. Our findings show that triplet-drug chemotherapy (FOLFOXIRI) combined with anti-EGFR antibody (panitumumab or cetuximab) represents a very effective therapeutic combination associated with a significant ORR and R0 rection rate for patients with molecularly unselected and surgically unresectable metastatic CRC.
Topics: Humans; Panitumumab; Cetuximab; Colorectal Neoplasms; Treatment Outcome; Colonic Neoplasms; Rectal Neoplasms; Antineoplastic Combined Chemotherapy Protocols; Fluorouracil; Leucovorin; Clinical Trials, Phase II as Topic; Randomized Controlled Trials as Topic
PubMed: 37978547
DOI: 10.1186/s12957-023-03256-7 -
World Journal of Gastrointestinal... Oct 2023Although common in lung cancer, somatic epidermal growth factor receptor () mutations are rarely found in colorectal cancer, occurring in approximately 3% of cases....
BACKGROUND
Although common in lung cancer, somatic epidermal growth factor receptor () mutations are rarely found in colorectal cancer, occurring in approximately 3% of cases. Treatment with anti-EGFR antibodies is commonplace, but tyrosine kinase inhibitors are not standard treatments in colorectal cancer. Here we report a case of sustained response to osimertinib in a colorectal cancer patient with an T790M mutation on cell-free DNA analysis.
CASE SUMMARY
A 72-year old woman with a past medical history of post-polio syndrome confined to a wheelchair, scoliosis and hypothyroidism presented with metastatic sigmoid colon adenocarcinoma with hepatic metastases. Next generation sequencing revealed a wild-type, microsatellite stable, PD-L1 negative malignancy. Mutations in and were also identified, as well as amplification. Cell-free DNA analysis revealed an T790M mutation. She was unable to tolerate first-line treatment with panitumumab, 5-fluorouracil and leucovorin, progressed on second-line treatment with trifluridine/tipiracil plus bevacizumab, and was unable to tolerate third-line treatment with regorafenib. She was started on fourth-line treatment with off-label osimertinib, with clinical response - decrease in size of hepatic metastases and a pericardial effusion. She remained on treatment with osimertinib for seven months.
CONCLUSION
This case shows the benefit of multi-gene sequencing assays to identify potential therapeutic options in patients with refractory disease.
PubMed: 37969405
DOI: 10.4251/wjgo.v15.i10.1829 -
Journal of Cutaneous Medicine and... Nov 2023Acneiform eruptions occur frequently and early in patients on epidermal growth factor receptor inhibitors (EGFRi). Identification of baseline patient risk factors would...
Acneiform eruptions occur frequently and early in patients on epidermal growth factor receptor inhibitors (EGFRi). Identification of baseline patient risk factors would prompt earlier referral to dermatology to optimize prevention and management. The primary objective of this retrospective study is to determine the association between clinical and demographic characteristics and the development of acneiform eruptions. A retrospective chart review was conducted on patients diagnosed with colon and head and neck cancers who started EGFRi between January 2017 and December 2021. Patients were followed until death or September 2022. Baseline demographic and clinical parameters were documented and patients were followed from the time of diagnosis to most recent visit for the development and management of an acneiform eruption. Regression analyses were performed to determine the association between baseline characteristics and the development of acneiform eruptions. A total of 66 patients were treated with cetuximab or panitumumab between 2017-2021 were included in the analysis. Forty-seven of the sixty-six patients developed an acneiform eruption while on EGFRi therapy (71.2%). Combination cancer therapy with another chemotherapeutic agent was associated with a lower risk of acneiform eruption (OR 0.03, = .027). No other baseline features were statistically associated with a lower risk of acneiform eruption. Acneiform eruptions are a common cutaneous adverse event of EGFRi therapy. Ongoing research is required to elucidate risk factors for the development of acneiform eruptions, to improve the quality of life of oncology patients.
Topics: Humans; Antibodies, Monoclonal; Antineoplastic Agents; Retrospective Studies; Quality of Life; Drug Eruptions; Acneiform Eruptions; ErbB Receptors; Risk Factors
PubMed: 37942582
DOI: 10.1177/12034754231211326 -
European Journal of Cancer (Oxford,... Dec 2023Upfront anti-EGFR therapy represents the standard of care for patients with left-sided, MSS/pMMR, RAS and BRAF wild-type mCRC. Molecular 'hyperselection' may...
BACKGROUND
Upfront anti-EGFR therapy represents the standard of care for patients with left-sided, MSS/pMMR, RAS and BRAF wild-type mCRC. Molecular 'hyperselection' may optimize EGFR inhibition by detecting additional resistance alterations.
MATERIALS AND METHODS
We used comprehensive genomic profiling on archival samples of elderly patients enrolled in the PANDA trial to detect: HER2 amplification/mutations; MET amplification; NTRK/ROS1/ALK/RET rearrangements; PIK3CA exon 20 mutations; PTEN alterations; AKT1 mutations; MAP2K1 mutations. We defined 'Gene Altered' (GA) patients whose tumour harboured at least one alteration, and 'Hyperselected' (HS) those without. Survival and tumour response outcomes were correlated to hyperselection status alone or combined with primary tumour sidedness or treatment arm.
RESULTS
Genomic alterations were detected in 41/147 patients (27.9%). PFS, OS and ORR were inferior in GA versus HS (median PFS: 7.6 versus 12.8 months, HR = 2.08, 95% CI: 1.43-3.03, p < 0.001; median OS: 20.0 versus 29.5 months, HR = 1.82, 95% CI:1.23-2.69, p = 0.002; ORR: 51% versus 71%; OR = 0.43, 95% CI: 0.21-0.91, p = 0.02). In the multivariable models, the impact of hyperselection on PFS and OS was confirmed. Lower ORR was observed with 5-FU/LV/panitumumab in GA (40% versus 62%), but not in HS (70% versus 72%). GA was associated with worse survival and response regardless of primary tumour sidedness, whereas in the HS subgroup, right-and left sided tumours had similar outcomes.
CONCLUSIONS
Molecular hyperselection and comprehensive genomic profiling have a potential usefulness in elderly patients with RAS/BRAF wild-type, pMMR/MSS mCRC, eligible for upfront EGFR inhibition.
Topics: Aged; Humans; Antibodies, Monoclonal; Antineoplastic Combined Chemotherapy Protocols; Colonic Neoplasms; Colorectal Neoplasms; ErbB Receptors; Fluorouracil; Panitumumab; Protein-Tyrosine Kinases; Proto-Oncogene Proteins; Proto-Oncogene Proteins B-raf; Rectal Neoplasms
PubMed: 37924647
DOI: 10.1016/j.ejca.2023.113396 -
World Journal of Surgical Oncology Oct 2023Adding anti-epidermal growth factor receptor (anti-EGFR) target agents to conversion therapy may improve the resection rates and survival of patients with potentially... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Adding anti-epidermal growth factor receptor (anti-EGFR) target agents to conversion therapy may improve the resection rates and survival of patients with potentially resectable metastatic colorectal cancer (mCRC). This study aims to analyze the efficacy and safety of additional anti-EGFR target agents.
METHODS
A systematic search was conducted on PubMed, Web of Science, Embase, and Cochrane Library. And all relevant studies published in English before January 2023 were collected to explore the impact of additional anti-EGFR targeted agent on the efficacy and safety of patients with potentially resectable mCRC (PROSPERO: CRD42022340523, https://www.crd.york.ac.uk/PROSPERO/ ).
RESULTS
This study included a total of 8 articles, including 2618 patients. The overall response rate (ORR) and R0 resection rates of the experimental group were higher than those of the control group, while there was no significant difference in progression-free survival (PFS) and overall survival (OS) between the two groups. In RAS/KRAS wild-type patients, the ORR (RR: 1.20, 95% Cl: 1.02-1.41, p = 0.03), R0 resection rate (RR: 1.60, 95% Cl: 1.17-2.20, p = 0.003), PFS (HR: 0.80, 95% Cl: 0.68-0.93, p = 0.003), and OS (HR: 0.87, 95% Cl: 0.76-0.99, p = 0.031) of the experimental group were higher than those of the control group. While in KRAS mutant patients, there was no statistical difference between the two groups in ORR, R0 resection rate, PFS, and OS.
CONCLUSION
The addition of anti-EGFR targeted agents can improve the prognosis of RAS/KRAS wild-type patients with potentially resectable mCRC, while KRAS mutant patients may not benefit. In addition, the overall safety factor was controllable.
Topics: Humans; Antibodies, Monoclonal; Antineoplastic Combined Chemotherapy Protocols; Cetuximab; Colorectal Neoplasms; ErbB Receptors; Proto-Oncogene Proteins p21(ras); Randomized Controlled Trials as Topic; Neoplasm Metastasis
PubMed: 37880688
DOI: 10.1186/s12957-023-03222-3 -
PharmacoEconomics - Open Nov 2023Cetuximab and panitumumab, two anti-EGFR therapies, are widely used for third-line therapy of metastatic colorectal cancer (mCRC) with wild-type KRAS, but there remains...
Real-World Cost Effectiveness of a Policy of KRAS Testing to Inform Cetuximab or Panitumumab for Third-Line Therapy of Metastatic Colorectal Cancer in British Columbia, Canada.
BACKGROUND
Cetuximab and panitumumab, two anti-EGFR therapies, are widely used for third-line therapy of metastatic colorectal cancer (mCRC) with wild-type KRAS, but there remains uncertainty around their cost effectiveness. The objective of this analysis was to conduct a real-world cost-effectiveness analysis of the policy change introducing KRAS testing and third-line anti-EGFR therapy mCRC in British Columbia (BC), Canada.
METHODS
We conducted secondary analysis of administrative data for a cohort of mCRC patients treated in BC in 2006-2015. Patients potentially eligible for KRAS testing and third-line therapy after the policy change (July 2009) were matched 2:1 to pre-policy patients using genetic matching on propensity score and baseline covariates. Costs and survival time were calculated over an 8-year time horizon, with bootstrapping to characterize uncertainty around endpoints. Cost effectiveness was expressed using incremental cost-effectiveness ratios (ICER) and the probability of cost effectiveness at a range of thresholds.
RESULTS
The cohort included 1757 mCRC patients (n = 456 pre-policy and n = 1304 post-policy; of those, n = 420 received cetuximab or panitumumab). There was a significant increase in survival and cost following the policy change. Adoption of KRAS testing and anti-EGFR therapy had an ICER of CA$73,759 per life-year gained (LYG) (95% CI 46,133-186,446). In scenario analysis, a reduction in cetuximab and panitumumab cost of at least 50% was required to make the policy change cost effective at a threshold of CA$50,000/LYG.
CONCLUSION
A policy of third-line anti-EGFR therapy informed by KRAS testing may be considered cost effective at thresholds above CA$70,000/LYG. Reduction in drug costs, through price discounts or potential future biosimilars, would make anti-EGFR therapy considerably more cost effective. By using real-world data for a large cohort with long follow-up we can assess the value of a policy of KRAS testing and anti-EGFR therapy achieved in practice.
PubMed: 37819586
DOI: 10.1007/s41669-023-00444-9 -
The Oncologist Dec 2023Colorectal cancer is the third most common cancer worldwide, and incidence is rising in younger individuals. Anti-EGFR antibodies, including cetuximab and panitumumab,... (Review)
Review
Colorectal cancer is the third most common cancer worldwide, and incidence is rising in younger individuals. Anti-EGFR antibodies, including cetuximab and panitumumab, have been incorporated into standard-of-care practice for patients with advanced disease. Herein, we review the molecular characteristics of these agents and the trials that lead to their approvals. Further, we discuss clinical implications of data regarding biomarkers that dictate treatment selection, different dosing strategies, and side effect management. Finally, we look towards the future and describe contexts in which these agents are currently being investigated clinically with a focus on combinations with MAPK-targeted therapies and immunotherapy. Overall, this review provides historical context, current clinical usage, and future directions for anti-EGFR antibodies in advanced colorectal cancer.
Topics: Humans; Antibodies, Monoclonal; Antineoplastic Agents; Antibodies, Monoclonal, Humanized; ErbB Receptors; Cetuximab; Colorectal Neoplasms
PubMed: 37774394
DOI: 10.1093/oncolo/oyad262 -
Current Oncology (Toronto, Ont.) Sep 2023Minimal Canadian data are available on the RAS testing rates, treatment patterns, and corresponding overall survival (OS) in metastatic colorectal cancer (mCRC)...
Minimal Canadian data are available on the RAS testing rates, treatment patterns, and corresponding overall survival (OS) in metastatic colorectal cancer (mCRC) patients. We conducted a population-based cohort study of left-sided RAS wild-type (WT) mCRC patients diagnosed between 1 January 2014 and 31 December 2019, and who were treated with first-line (1L) chemotherapy plus the epidermal growth factor receptor inhibitor panitumumab, chemotherapy plus bevacizumab, or chemotherapy alone, in Alberta, Canada, using electronic medical records and administrative health system data. Of the 2721 patients identified with left-sided mCRC, 320 patients with RAS WT mCRC were treated with 1L systemic therapy: chemotherapy plus panitumumab (n = 64), chemotherapy plus bevacizumab (n = 52), or chemotherapy alone (n = 204). Only 65% and 39% of the 320 1L-treated patients initiated second- and third-line therapy, respectively. A total of 71% of individuals with treated left-sided mCRC underwent RAS testing. The median OS for mCRC patients with RAS WT left-sided tumours was higher for patients treated with 1L panitumumab plus chemotherapy (34.3 months; 95% CI: 23.8-39.6) than for patients who received 1L chemotherapy alone (30.0 months; 95% CI: 24.9-34.1) or 1L bevacizumab plus chemotherapy (25.6 months; 95% CI: 21.2-35.7). These findings highlight an unmet need in left-sided RAS WT mCRC, with relatively few individuals receiving a biologic agent in combination with chemotherapy in the 1L setting, a high rate of attrition between lines, and a need for increased RAS testing before treatment initiation.
PubMed: 37754511
DOI: 10.3390/curroncol30090596 -
Cancers Sep 2023Anti-EGFR antibodies combined with chemotherapy doublets are a cornerstone of the upfront treatment of colorectal cancer. RAS and BRAF mutations are established negative...
The Impact of Sidedness on the Efficacy of Anti-EGFR-Based First-Line Chemotherapy in Advanced Colorectal Cancer Patients in Real-Life Setting-A Nation-Wide Retrospective Analysis (RACER).
Anti-EGFR antibodies combined with chemotherapy doublets are a cornerstone of the upfront treatment of colorectal cancer. RAS and BRAF mutations are established negative predictive factors for such therapy. The primary tumour located in the proximal colon has recently emerged as another negative predictive factor. We have conducted a retrospective multicentre study to collect data on real-world population characteristics, practice patterns, and outcomes in patients with metastatic colorectal cancer treated in a first-line setting with either cetuximab or panitumumab in combination with either FOLFOX or FOLFIRI chemotherapy. The presented analysis focuses on the impact of the primary tumour location. 126 of 842 patients analysed (15.0%) had proximal primary. It was associated with a lower BMI at diagnosis, mucinous histology, and peritoneal metastases. It was also associated with inferior treatment outcomes in terms of response ratio: 59.4% vs. 74.22% (odds ratio [OR] 0.51, 95% CI 0.33-0.78, = 0.010), and median depth of response: -36.7% vs. -50.0% ( = 0.038). There was only a borderline non-significant trend for inferior PFS in patients with proximal tumours. OS data was incomplete. The presented analysis confirms the negative impact of tumour sidedness on the efficacy of an upfront anti-EGFR-chemotherapy combination and provides valuable data on real-world population characteristics.
PubMed: 37686636
DOI: 10.3390/cancers15174361