Dataset Information

Withholding the Introduction of Anti-Epidermal Growth Factor Receptor: Impact on Outcomes in RAS Wild-Type Metastatic Colorectal Tumors: A Multicenter AGEO Study (the WAIT or ACT Study).

ABSTRACT: BACKGROUND:Patients with RAS wild-type (WT) nonresectable metastatic colorectal cancer (mCRC) may receive either bevacizumab or an anti-epidermal growth factor receptor (EGFR) combined with first-line, 5-fluorouracil-based chemotherapy. Without the RAS status information, the oncologist can either start chemotherapy with bevacizumab or wait for the introduction of the anti-EGFR. Our objective was to compare both strategies in a routine practice setting. MATERIALS AND METHODS:This multicenter, retrospective, propensity score-weighted study included patients with a RAS WT nonresectable mCRC, treated between 2013 and 2016 by a 5-FU-based chemotherapy, with either delayed anti-EGFR or immediate anti-vascular endothelial growth factor (VEGF). Primary criterion was overall survival (OS). Secondary criteria were progression-free survival (PFS) and objective response rate (ORR). RESULTS:A total of 262 patients (129 in the anti-VEGF group and 133 in the anti-EGFR group) were included. Patients receiving an anti-VEGF were more often men (68% vs. 56%), with more metastatic sites (>2 sites: 15% vs. 9%). The median delay to obtain the RAS status was 19?days (interquartile range: 13-26). Median OS was not significantly different in the two groups (29 vs. 30.5 months, p = .299), even after weighting on the propensity score (hazard ratio [HR] =?0.86, 95% confidence interval [CI], 0.69-1.08, p = .2024). The delayed introduction of anti-EGFR was associated with better median PFS (13.8 vs. 11.0 months, p = .0244), even after weighting on the propensity score (HR = 0.74, 95% CI, 0.61-0.90, p = .0024). ORR was significantly higher in the anti-EGFR group (66.7% vs. 45.6%, p = .0007). CONCLUSION:Delayed introduction of anti-EGFR had no deleterious effect on OS, PFS, and ORR, compared with doublet chemotherapy with anti-VEGF. IMPLICATIONS FOR PRACTICE:For RAS/RAF wild-type metastatic colorectal cancer, patients may receive 5-fluorouracil-based chemotherapy plus either bevacizumab or an anti-epidermal growth factor receptor (EGFR). In daily practice, the time to obtain the RAS status might be long enough to consider two options: to start the chemotherapy with bevacizumab, or to start without a targeted therapy and to add the anti-EGFR at reception of the RAS status. This study found no deleterious effect of the delayed introduction of an anti-EGFR on survival, compared with the introduction of an anti-vascular endothelial growth factor from cycle 1. It is possible to wait one or two cycles to introduce the anti-EGFR while waiting for RAS status.

SUBMITTER: Palmieri LJ

PROVIDER: S-EPMC7011620 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Withholding the Introduction of Anti-Epidermal Growth Factor Receptor: Impact on Outcomes in RAS Wild-Type Metastatic Colorectal Tumors: A Multicenter AGEO Study (the WAIT or ACT Study).

Palmieri Lola-Jade LJ Mineur Laurent L Tougeron David D Rousseau Benoît B Granger Victoire V Gornet Jean-Marc JM Smith Denis D Lievre Astrid A Galais Marie-Pierre MP Doat Solene S Pernot Simon S Bignon-Bretagne Anne-Laure AL Metges Jean-Philippe JP Baba-Hamed Nabil N Michel Pierre P Obled Stéphane S Vitellius Carole C Bouche Olivier O Saban-Roche Léa L Buecher Bruno B des Guetz Gaëtan G Locher Christophe C Trouilloud Isabelle I Goujon Gaël G Dior Marie M Manfredi Sylvain S Soularue Emilie E Phelip Jean-Marc JM Henriques Julie J Vernery Dewi D Coriat Romain R

The oncologist 20191002 2

<h4>Background</h4>Patients with RAS wild-type (WT) nonresectable metastatic colorectal cancer (mCRC) may receive either bevacizumab or an anti-epidermal growth factor receptor (EGFR) combined with first-line, 5-fluorouracil-based chemotherapy. Without the RAS status information, the oncologist can either start chemotherapy with bevacizumab or wait for the introduction of the anti-EGFR. Our objective was to compare both strategies in a routine practice setting.<h4>Materials and methods</h4>This ...[more]

PMID: 32043796

Similar Datasets

Project description:BackgroundUnderstanding how frailty affects patients listed for transplantation has been identified as a priority research need. Frailty may be associated with a high risk of death or wait-list withdrawal, but this has not been evaluated in a large multicenter cohort of Canadian wait-listed patients.ObjectiveThe primary objective is to evaluate whether frailty is associated with death or permanent withdrawal from the transplant wait list. Secondary objectives include assessing whether frailty is associated with hospitalization, quality of life, and the probability of being accepted to the wait list.DesignProspective cohort study.SettingSeven sites with established renal transplant programs that evaluate patients for the kidney transplant wait list.PatientsIndividuals who are being considered for the kidney transplant wait list.MeasurementsWe will assess frailty using the Fried Phenotype, a frailty index, the Short Physical Performance Battery, and the Clinical Frailty Scale at the time of listing for transplantation. We will also assess frailty at the time of referral to the wait list and annually after listing in a subgroup of patients.MethodsThe primary outcome of the composite of time to death or permanent wait-list withdrawal will be compared between patients who are frail and those who are not frail and will account for the competing risks of deceased and live donor transplantation. Secondary outcomes will include number of hospitalizations and length of stay, and in a subset, changes in frailty severity over time, change in quality of life, and the probability of being listed. Recruitment of 1165 patients will provide >80% power to identify a relative hazard of ≥1.7 comparing patients who are frail to those who are not frail for the primary outcome (2-sided α = .05), whereas a more conservative recruitment target of 624 patients will provide >80% power to identify a relative hazard of ≥2.0.ResultsThrough December 2019, 665 assessments of frailty (inclusive of those for the primary outcome and all secondary outcomes including repeated measures) have been completed.LimitationsThere may be variation across sites in the processes of referral and listing for transplantation that will require consideration in the analysis and results.ConclusionsThis study will provide a detailed understanding of the association between frailty and outcomes for wait-listed patients. Understanding this association is necessary before routinely measuring frailty as part of the wait-list eligibility assessment and prior to ascertaining the need for interventions that may modify frailty.Trial registrationNot applicable as this is a protocol for a prospective observational study.

Project description:BackgroundThrough Community Care Networks (CCNs) implemented with the VA MISSION Act, VA expanded provider contracting and instituted network adequacy standards for Veterans' community care.ObjectiveTo determine whether early CCN implementation impacted community primary care (PC) appointment wait times overall, and by rural/urban and PC shortage area (HPSA) status.DesignUsing VA administrative data from February 2019 through February 2020 and a difference-in-differences approach, we compared wait times before and after CCN implementation for appointments scheduled by VA facilities that did (CCN appointments) and did not (comparison appointments) implement CCNs. We ran regression models with all appointments, and stratified by rural/urban and PC HPSA status. All models adjusted for Veteran characteristics and VA facility-level clustering.Appointments13,720 CCN and 40,638 comparison appointments.Main measuresWait time, measured as number of days from authorization to use community PC to a Veteran's first corresponding appointment.Key resultsOverall, unadjusted wait times increased by 35.7 days ([34.4, 37.1] 95% CI) after CCN implementation. In adjusted analysis, comparison wait times increased on average 33.7 days ([26.3, 41.2] 95% CI, p < 0.001) after CCN implementation; there was no significant difference for CCN wait times (across-group mean difference: 5.4 days, [-3.8, 14.6] 95% CI, p = 0.25). In stratified analyses, comparison wait time increases ranged from 29.6 days ([20.8, 38.4] 95% CI, p < 0.001) to 42.1 days ([32.9, 51.3] 95% CI, p > 0.001) after CCN implementation, while additional differences for CCN appointments ranged from 13.4 days ([3.5, 23.4] 95% CI, p = 0.008) to -15.1 days ([-30.1, -0.1] 95% CI, p = 0.05) for urban and PC HPSA appointments, respectively.ConclusionsAfter early CCN implementation, community PC wait times increased sharply at VA facilities that did and did not implement CCNs, regardless of rural/urban or PC HPSA status, suggesting community care demand likely overwhelmed VA resources such that CCNs had limited impact.

Project description:: Background: The optimal anti-angiogenic strategy as second-line treatment in RAS wild-type metastatic colorectal cancer (mCRC) treated with anti-EGFR (Epidermal Growth Factor Receptor) based first-line treatment is still debated. This multicenter, real-world, retrospective study is aimed at evaluating the effectiveness of second-line Bevacizumab- and Aflibercept-based treatments after an anti-EGFR based first-line regimen. Clinical outcomes measured were: objective response rate (ORR), progression free survival (PFS), overall survival (OS) and adverse events (AEs) profiles. From February 2011 to October 2019, 277 consecutive mCRC patients received Bevacizumab-based (228, 82.3%) or Aflibercept-based (49, 17.7%) regimen. No significant difference was found regarding ORR. The median follow-up was 27.7 months (95%CI: 24.7-34.4). Aflibercept-treated group had a significantly shorter PFS compared to Bevacizumab-treated group (5.6 vs. 7.1 months, respectively) (HR = 1.34 (95%CI: 0.95-1.89); p = 0.0932). The median OS of the Bevacizumab-treated group and Aflibercept-treated group was 16.2 (95%CI: 15.3-18.1) and 12.7 (95%CI: 8.8-17.5) months, respectively (HR= 1.31 (95%CI: 0.89-1.93) p = 0.16). After adjusting for the key covariates (age, gender, performance status, number of metastatic sites and primary tumor side) Bevacizumab-based regimens revealed to be significantly related with a prolonged PFS (HR = 1.44 (95%CI: 1.02-2.03); p = 0.0399) compared to Aflibercept-based regimens, but not with a prolonged OS (HR = 1.47 (95%CI: 0.99-2.17); p = 0.0503). The incidence of G3/G4 VEGF inhibitors class-specific AEs was 7.5% and 26.5% in the Bevacizumab-treated group and the Aflibercept-treated group, respectively (p = 0.0001). Our analysis seems to reveal that Bevacizumab-based regimens have a slightly better PFS and class-specific AEs profile compared to Aflibercept-based regimen as second-line treatment of RAS wild-type mCRC patients previously treated with anti-EGFR based treatments. These results have to be taken with caution and no conclusive considerations are allowed.

Project description:Endogenous and synthetic glucocorticoids (GCs) regulate epidermal development and combat skin inflammatory diseases. GC actions can be mediated through the GC receptor (GR) and/or the mineralocorticoid receptor (MR), highly homologous ligand-activated transcription factors. While the role of GR as a potent anti-inflammatory mediator is well known, that of MR is not as clear, nor is whether these receptors cooperate or antagonize each other in the epidermis. To address this, we generated mice with epidermal-specific loss of both receptors (double knockout, DKO), and analyzed the phenotypical and functional consequences relative to single KOs or controls (CO). At birth, DKO epidermis displayed a phenotype of defective differentiation and inflammation, which was more severe than in either single KO, featuring neutrophil-containing infiltrates, and gene dysregulation characteristic of human psoriatic lesions. This phenotype resolved spontaneously. However, in adulthood, single or combined loss of GC receptors increased susceptibility to inflammation and hyperproliferation triggered by phorbol ester which, different to CO, was not effectively counteracted by GC treatment. Also, DKOs were more susceptible to imiquimod-induced psoriasis than CO showing severe defective epidermal differentiation and microabcesses while single KOs showed an intermediate response. Immortalized DKO keratinocytes featured increased proliferation kinetics and reduced cell size, a unique phenotype relative to single KO cells. The lack of GR and MR in keratinocytes, individual or combined, caused constitutive increases in p38 and ERK activities, which were partially reversed upon reinsertion of receptors into DKO cells. DKO keratinocytes also displayed significant increases in AP-1 and NF-?B transcriptional activities, which were partially rescued by ERK and p38 inhibition, respectively. Reinsertion of GR and MR in DKO keratinocytes resulted in physical and cooperative functional interactions that restored the transcriptional response to GCs. In conclusion, our data have revealed that epidermal GR and MR act cooperatively to regulate epidermal development and counteract skin inflammation.

Dataset Information

Withholding the Introduction of Anti-Epidermal Growth Factor Receptor: Impact on Outcomes in RAS Wild-Type Metastatic Colorectal Tumors: A Multicenter AGEO Study (the WAIT or ACT Study).

Publications

Withholding the Introduction of Anti-Epidermal Growth Factor Receptor: Impact on Outcomes in RAS Wild-Type Metastatic Colorectal Tumors: A Multicenter AGEO Study (the WAIT or ACT Study).

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets