Impact of Delayed Addition of Anti-EGFR Monoclonal Antibodies on the Outcome of First-Line Therapy in Metastatic Colorectal Cancer Patients: a Retrospective Registry-Based Analysis

Fiala, Ondřej; Veškrňová, Veronika; Chloupková, Renata; Poprach, Alexandr; Kiss, Igor; Kopečková, Kateřina; Dušek, Ladislav; Slavíček, Lubomír; Kohoutek, M; Fínek, Jindřich; Svoboda, Marek; Petruželka, Luboš; Boublíková, Ludmila; Dvořák, Josef; Melichar, Bohuslav; Büchler, Tomáš

doi:10.1007/s11523-018-0597-7

Cited by 6 publications

(5 citation statements)

References 38 publications

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“…The comparison of our findings to other studies using realworld data from Europe is hampered regarding studies using certain criteria to select patients, e.g., if they excluded patients with early disease progression (11,12) or focused on patients with metachronous metastases (13). A study from the UK based on medical records, which included unselected patients with advanced CRC (N = 714) similar to our approach, confirmed our findings.…”

Section: Discussionsupporting

confidence: 68%

“…So far, available studies using real-world data such as administrative claims are often based on data from the United States (8)(9)(10). To our knowledge, real-world evidence based on routinely collected data on utilization of biologics in CRC patients from Europe is limited to two studies from the Czech Republic using data from a specific drug registry, one study from the Netherlands using data from a regional cancer registry, and one from Italy based on five regional cancer registries (11)(12)(13)(14). Large claims or medical record databases from Europe have thus not been used for this purpose so far.…”

Section: Introductionmentioning

confidence: 99%

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Characteristics and Absolute Survival of Metastatic Colorectal Cancer Patients Treated With Biologics: A Real-World Data Analysis From Three European Countries

et al. 2021

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Introduction: Biologics were approved for the treatment of advanced colorectal cancer (CRC) based on favorable benefit-risk-assessments from randomized controlled trials (RCTs), but evidence on their use in the real-world setting is scarce. Based on descriptive analyses we therefore aimed to assess characteristics and survival of CRC patients treated with biologics using large healthcare databases from three European countries (Netherlands, Italy, Germany).Methods: We included CRC patients treated with a biologic in 2010 or 2014 and characterized them regarding age, sex, comorbidities, and absolute survival.Results: Among 4,758 patients, the mean age ranged from 64.8 to 66.8 years, the majority was male, and comorbidities used as exclusion criteria in RCTs were coded in up to 30% of these patients. The proportion of bevacizumab users decreased between 2010 (72–93%) and 2014 (63–85%). In 2014, the absolute 12-month survival in new users was 64% (95% CI 51–77%), 56% (30–80%), and 61% (58–63%) in the Dutch, Italian, and German database, respectively, varying by age and comorbidity.Conclusions: Our study suggests that in the real-world setting, CRC patients treated with biologics are older and less selected regarding comorbidities compared to patients in RCTs, potentially explaining the relatively low 12-month survival we found. Treatment decisions in the real-world setting may require careful evaluation given that the risk-benefit ratio may vary depending on age and co-existing conditions.

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Section: Discussionsupporting

confidence: 68%

Section: Introductionmentioning

confidence: 99%

Characteristics and Absolute Survival of Metastatic Colorectal Cancer Patients Treated With Biologics: A Real-World Data Analysis From Three European Countries

et al. 2021

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“…Indeed, the ORR in the anti‐EGFR group was 67% and 72% in our study and in the FIRE‐3 study, respectively. Furthermore, a retrospective study compared in metastatic colorectal cancer RAS WT the introduction of the anti‐EGFR at the first cycle versus the introduction at the second cycle versus the introduction at the third or fourth cycle, without any detrimental effect on OS and ORR of delayed addition of anti‐EGFR agents . Therefore, the strategy of a delayed introduction of an anti‐EGFR appeared feasible and not deleterious compared with doublet chemotherapy with an anti‐VEGF.…”

Section: Discussionmentioning

confidence: 99%

“…We included 10 aflibercept‐treated patients from a phase II trial, which may have been a selection bias. We did not compare the immediate introduction of the anti‐EGFR to their delayed introduction, but Fiala et al compared immediate anti‐EGFR to delayed anti‐EGFR and suggested that there was no difference between those two groups. Our study compared for the first time the strategy of a delayed introduction of an anti‐EGFR to the recommended targeted therapy started at cycle 1.…”

Section: Discussionmentioning

confidence: 99%

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)

et al. 2019

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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.

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“…39 In a recently published study, we report that limited pretreatment with chemotherapy before the start of EGFRi could be associated with modestly improved outcomes. 40…”

Section: Discussionmentioning

confidence: 99%

Sequential therapy with bevacizumab and EGFR inhibitors for metastatic colorectal carcinoma: a national registry-based analysis

Büchler

Chloupková

Poprach

et al. 2018

CMAR

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Although inhibitors of vascular endothelial growth factor and inhibitors of epidermal growth factor receptor (EGFRi) are commonly used for the treatment of metastatic colorectal cancer (mCRC), the optimal sequencing of these agents is currently unclear. Methods: A national registry of targeted therapies was used to analyze baseline characteristics and outcomes of patients with mCRC and wild-type KRAS exon 2 status who received bevacizumab and EGFRi (cetuximab or panitumumab) as a part of first-and second-line treatment in either sequence. Results: The cohort included 490 patients (181 patients treated with first-line EGFRi and second-line bevacizumab and 309 patients treated with first-line bevacizumab and second-line EGFRi). Median overall survival (OS) from the initiation on first-line therapy was similar for patients treated with either sequence, reaching 31.8 (95% CI 27.5-36.1) vs 31.4 months (95% CI 27.8-35.0) for EGFRi → bevacizumab vs bevacizumab → EGFRi cohort, respectively. Time from first-line initiation to progression on the second-line therapy [progression-free survival (PFS)] was 21.1 (95% CI 19.3-23.0) vs 19.3 months (95% CI 17.3-21.3) for bevacizumab → EGFRi vs EGFRi → bevacizumab cohort, respectively (P=0.016). Conclusion: This retrospective analysis of real-world data of patients with wild-type KRAS exon 2 mCRC showed no differences in OS between cohorts treated with bevacizumab → EGFRi vs the reverse sequence while combined PFS favored the bevacizumab → EGFRi sequence.

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Impact of Delayed Addition of Anti-EGFR Monoclonal Antibodies on the Outcome of First-Line Therapy in Metastatic Colorectal Cancer Patients: a Retrospective Registry-Based Analysis

Cited by 6 publications

References 38 publications

Characteristics and Absolute Survival of Metastatic Colorectal Cancer Patients Treated With Biologics: A Real-World Data Analysis From Three European Countries

Characteristics and Absolute Survival of Metastatic Colorectal Cancer Patients Treated With Biologics: A Real-World Data Analysis From Three European Countries

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)

Sequential therapy with bevacizumab and EGFR inhibitors for metastatic colorectal carcinoma: a national registry-based analysis

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