Cetuximab with irinotecan or oxaliplatin for first-line metastatic colorectal cancer: Effectiveness in the EREBUS cohort compared to pivotal trials.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e14542-e14542
Author(s):  
Annie Fourrier-Réglat ◽  
Magali Rouyer ◽  
Pernelle Noize ◽  
Emmanuelle Bignon ◽  
Alise Le Monies ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Treatment Initiation ◽  
Response Rate ◽  
Real Life ◽  
Wild Type ◽  
First Line ◽  
Multicenter Cohort Study ◽  
Baseline Characteristics ◽  
One Year

e14542 Background: Cetuximab (CTX) has demonstrated improved survival outcomes in metastatic colorectal cancer (mCRC) but information from real-life use is sparse. Here, CTX survival and safety outcomes in real-life are compared to those observed in OPUS and CRYSTAL trials. Methods: EREBUS is a French multicenter cohort study that included over two years (2009-2010) patients with unresectable mCRC and wild-type KRAS initiating CTX as 1st-line therapy in 65 centres and followed for 12 months from treatment initiation. Results: We included 389 patients treated with a combination of CTX with irinotecan-based (56.0%) or CTX with oxaliplatin-based (37.8%) chemotherapy. The main characteristics, safety, response rate, and one year survival of this cohort are presented in the Table below in parallel with results obtained in pivotal trials. Conclusions: Despite differences in baseline characteristics between real-life and pivotal trials (such as ECOG status), the response rate and PFS were comparable in mCRC patients with wt KRAS treated with 1st-line CTX. The nature of adverse events was in-line with the trials but the frequency was lower probably owing to under-notification in real-life. [Table: see text]

First line treatment of metastatic colorectal cancer: Are clinical trial results reproducible in real-life practice?

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 836-836
Author(s):  
Ron Lewin ◽  
Omer Gal ◽  
Aaron Sulkes ◽  
Noa Gordon ◽  
Irit Ben-Aharon ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Performance Status ◽  
Group Analysis ◽  
Real Life ◽  
Line Treatment ◽  
Wild Type ◽  
First Line ◽  
Primary Tumor Site ◽  
Ras Status

836 Background: Treatment of metastatic colorectal cancer (mCRC) has greatly advanced over the past decade, based on data from randomized controlled trials (RCTs). This raises the question whether results of RCTs, performed on selected patients (pts), do reflect outcomes in real-life practice. The aim of this study was to summarize our experience in the treatment of mCRC and compare it to data reported in RCTs. Methods: A retrospective single-institution study on consecutive mCRC pts treated with first-line bevacizumab-containing regimens in our institute between 2006 and 2014. Results: The study included 300 pts, of whom 54% were males. Median age was 67 years (range 28-90), 26% aged ≥ 75 years. ECOG performance status was ≤1 in 93%. The primary tumor site was right colon in 37%, left colon in 40%, rectal in 23% and 1% of pts had synchronous tumors. RAS status was available in 60%, of whom 55% had wild-type alleles. 46% of pts had a single metastatic site, including 27% with liver-limited disease, and 54% had multiple metastatic sites. Irinotecan-based chemotherapy was used in 66%, oxaliplatin-based chemotherapy in 29% and flouropyrimidine monotherapy in 5%. Curative metastasectomy during 1st line treatment was performed in 29%. Grade ≥3 hematological and non-hematological toxicities were reported in 24% and 38% of pts, respectively. Second and third line treatments were administered to 75% and 66% of pts, respectively; 73% of pts received both irinotecan and oxaliplatin through their treatment course and 76% of those with wild-type RAS were treated with anti-EGFR therapy. Overall response rate and disease control rate were 69% and 89%, respectively. Median progression-free survival (PFS) and overall survival (OS) were 17 and 28 months, respectively. In a sub-group analysis on "RCT-like population", excluding pts ≥ 75 years, ECOG PS ≥ 3 and/or mutated/unknown RAS status, median PFS and OS were 15 and 29 months, respectively. Conclusions: The results of this study suggest that, if adhered to international clinical guidelines, outcomes reported in RCTs are indeed reproducible in routine clinical practice in unselected real-life pts. Additional data, with more pts and longer follow-up, will be presented.

scholarly journals Post-Induction Management in Patients With Left-Sided RAS and BRAF Wild-Type Metastatic Colorectal Cancer Treated With First-Line Anti-EGFR-Based Doublet Regimens: A Multicentre Study

2021 ◽  
Vol 11 ◽  
Author(s):  
Alessandro Parisi ◽  
Alessio Cortellini ◽  
Olga Venditti ◽  
Roberto Filippi ◽  
Lisa Salvatore ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Disease Progression ◽  
Objective Response ◽  
Real Life ◽  
Treatment Strategies ◽  
Induction Treatment ◽  
Wild Type ◽  
First Line ◽  
Post Induction

BackgroundFew data regarding post-induction management following first-line anti-epidermal growth factor receptor (EGFR)-based doublet regimens in patients with left-sided RAS/BRAF wild-type metastatic colorectal cancer (mCRC) are available.MethodsThis multicenter, retrospective study aimed at evaluating clinicians’ attitude, and the safety and effectiveness of post-induction strategies in consecutive patients affected by left-sided RAS/BRAF wild-type mCRC treated with doublet chemotherapy plus anti-EGFR as first-line regimen, who did not experience disease progression within 6 months from induction initiation, at 21 Italian and 1 Spanish Institutions. The measured clinical outcomes were: progression-free survival (PFS), overall survival (OS), adverse events, and objective response rate (ORR).ResultsAt the data cutoff, among 686 consecutive patients with left-sided RAS/BRAF wild-type mCRC treated with doublet plus anti-EGFR as first-line regimen from March 2012 to October 2020, 355 eligible patients have been included in the present analysis. Among these, 118 (33.2%), 66 (18.6%), and 11 (3.1%) received a maintenance with 5-fluorouracil/leucovorin (5FU/LV)+anti-EGFR, anti-EGFR, and 5FU/LV, respectively, while 160 (45.1%) patients continued induction treatment (non-maintenance) until disease progression, unacceptable toxicity, patient decision, or completion of planned treatment. The median period of follow-up for the overall population was 33.7 months (95%CI = 28.9–35.6). The median PFS values of the 5FU/LV+anti-EGFR, anti-EGFR, 5FU/LV, and non-maintenance cohorts were 16.0 (95%CI = 14.3–17.7, 86 events), 13.0 (95%CI = 11.4–14.5, 56 events), 14.0 (95%CI = 8.1–20.0, 8 events), and 10.1 months (95%CI = 9.0–11.2, 136 events), respectively (p < 0.001). The median OS values were 39.6 (95%CI = 31.5–47.7, 43 events), 36.1 (95%CI = 31.6–40.7, 36 events), 39.5 (95%CI = 28.2–50.8, 4 events), and 25.1 months (95%CI = 22.6–27.6, 99 events), respectively (p < 0.001). After adjusting for key covariates, a statistically significant improvement in PFS in favor of 5FU/LV+anti-EGFR (HR = 0.59, 95%CI = 0.44–0.77, p < 0.001) and anti-EGFR (HR = 0.71, 95%CI = 0.51–0.98, p = 0.039) compared to the non-maintenance cohort was found. Compared to the non-maintenance cohort, OS was improved by 5FU/LV+anti-EGFR (HR = 0.55, 95%CI = 0.38–0.81, p = 0.002) and, with marginal significance, by anti-EGFR (HR = 0.67, 95%CI = 0.51–0.98, p = 0.051). No difference was found in ORR. Any grade non-hematological and hematological events were generally higher in the non-maintenance compared to the maintenance cohorts.ConclusionAmong the treatment strategies following an anti-EGFR-based doublet first-line induction regimen in patients affected by left-sided RAS/BRAF wild-type mCRC treated in a “real-life” setting, 5FU/LV+anti-EGFR resulted the most adopted, effective, and relatively safe regimen.

Is oxaliplatin a good partner for EGFR monoclonal antibodies as first-line treatment in KRAS wild-type metastatic colorectal cancer? A meta-analysis.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e14645-e14645
Author(s):  
Feng Wen ◽  
Qiu Li ◽  
Ruilei Tang ◽  
Yaxiong Sang ◽  
Meng Li ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Monoclonal Antibodies ◽  
Metastatic Colorectal Cancer ◽  
Response Rate ◽  
Meta Analysis ◽  
Fixed Effect ◽  
Line Treatment ◽  
Wild Type ◽  
First Line ◽  
First Line Treatment

e14645 Background: This meta-analysis was performed to determine whether the addition of monoclonal antibodies (mAbs) of epidermal growth factor receptor (EGFR) to oxaliplatin-based chemotherapy treatment improves efficacy in KRAS wild-type metastatic colorectal cancer (mCRC), and whether infusional 5-fluorouracil (5-FU) and oxaliplatin is a preferred combination for EGFR mAbs. Methods: Oxaliplatin (including treatment), EGFR mAbs, first-line treatment, KRAS wild-type, and mCRC were used as key words. The PRIME, OPUS, COIN, and NORDIC VII trials were identified by two independent authors. Time-to-event outcomes of overall survival (OS) and progression-free survival (PFS) were analyzed using HRs (Hazard Ratios) with fixed effect, and response rate (RR) using odd ratios (OR) with fixed effect. Results: A total of 1,767 patients who were KRAS wild-type were included in this meta-analysis, with 866 patients in the mAbs and chemotherapy combination group and 901 patients in the chemotherapy alone group. The addition of mAbs to oxaliplatin-based chemotherapy in patients with KRAS wild-type mCRC as first-line treatment resulted in significant improvements in PFS (HR=0.88; 95% confidence interval (CI), 0.79 to 0.99; P=0.03) and response rate (RR) (OR = 1.38; 95% CI, 1.14 to 1.66; P = 0.009) compared with chemotherapy alone, but the difference in OS was not significant (HR=0.96; 95% CI, 0.85 to 1.08; P=0.48). However, the differences neither in OS nor in PFS were not significant when mAbs were added to bolus 5-FU or capecitabine-based regimens compared with chemotherapy alone, whereas PFS improved with an infusional 5-FU and oxaliplatin combination (P=0.06; PFS, HR=0.76; 95% CI, 0.65 to 0.86; P=0.0002), and even OS was marginally significant. Conclusions: Oxaliplatin and infusional 5-FU regimen tends to be a better backbone combination with EGFR mAbs as first-line treatment in KRAS wild-type mCRC.

Real-world treatment outcomes from nationwide ONCO-colon Turkey registry in RAS wi̇ld-type patients treated with biologics first-line metastatic colorectal cancer.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e15561-e15561
Author(s):  
Umut Kefeli ◽  
Cagatay Arslan ◽  
Mahmut Emre Yildirim ◽  
Abdurrahman Isikdogan ◽  
Nuri Karadurmus ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Clinical Trials ◽  
Metastatic Colorectal Cancer ◽  
Real World ◽  
Response Rate ◽  
Wild Type ◽  
First Line ◽  
Real World Data ◽  
Mutant Type ◽  
Anti Vegf

e15561 Background: Efficacy of anti-angiogenic and anti-EGFR agents has been demonstrated metastatic colorectal cancer (mCRC). Real-world evidence is especially important to detect the findings of patients outside of clinical trials. It complements together with clinical trials. However, there are a few studies that evaluated these treatments with biologics in the real-world setting. Recognizing the change that has occurred over the years will also shed light on future approaches. Therefore, we aimed to investigate the real-world data of patients with RAS-wild type mCRC. Methods: Medical records from 28 centers were collected for patients diagnosed with RAS wild-type mCRC between January 2016 and April 2019 and were included into the study. Histopathological, molecular and clinical characteristics of the patients were recorded. The treatment duration, response rate, progression-free survival and safety results were determined. Also, changes over the years were compared. Patients were compared according to the first-line biological treatments as anti-EGFR group (Group A and B) (panitumumab and cetuximab) and anti-VEGF group (group C). Results: Patients with KRAS mutant type were 43,6% and 6.1% patients were NRAS mutant type. A total of 1064 patients with documented RAS wild-type status were evaluated. 33%, 37% and 30% of all first line patients were treated with regimen including panitumumab, cetuximab and anti-VEGF, respectively. The median follow-up time was 24 (1-59) months. Median age was 61 (17-88) years. Thirty-five percent of the patients were female. Twenty percent of the patients had a right-sided colon tumor. Patients received median 6 cycles of treatment. Also, responded patients received median 6 cycles of treatment as maintenance treatment with biologics plus fluoropyrimidine. Overall response rate was 46,4%, 41,9% and 41,5% in A, B and C group respectively (p = 0,170). The median OS was 26, 27, and 23 months in A, B and C group respectively (p = 0.044). The median PFS of the patients in first-line setting that received panitumumab, cetuximab and bevacizumab were 11.6 (SE:0,6; 95% CI: 10.4-12.7), 11.0 (SE:0,5; 95% CI: 9.9-12.0), and 9.6 (SE:0,4; 95% CI: 8.8-10.4) months respectively (p = 0.012). In univariate analysis, female gender (p = 0.030), left sided tumors(p = 0.001), ECOG performance status (PS) 0-1 (p = 0.001), normal CEA level at initial diagnosis(p = 0.001) and treatment with anti-EGFR agents(p = 0.016) were found as favorable factors. PS 0-1 and normal CEA level at initial diagnosis were found as independent prognostic factors in multivariate analysis (p = 0.049, p = 0.031 respectively). Conclusions: This analysis of real-world data confirms the comparable efficacy of anti-EGFR agents in RAS-wild type mCRC. However, anti-EGFR treatment provides PFS and OS advantage when compared with anti-VEGF treatment in these patients.

scholarly journals Evidence-Based Second-Line Treatment in RAS Wild-Type/Mutated Metastatic Colorectal Cancer in the Precision Medicine Era

2021 ◽  
Vol 22 (14) ◽  
pp. 7717
Author(s):  
Guido Giordano ◽  
Pietro Parcesepe ◽  
Giuseppina Bruno ◽  
Annamaria Piscazzi ◽  
Vincenzo Lizzi ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Checkpoint Inhibitors ◽  
Line Treatment ◽  
Second Line ◽  
Wild Type ◽  
First Line ◽  
Braf Mutations ◽  
Mutational Status ◽  
First Line Treatment

Target-oriented agents improve metastatic colorectal cancer (mCRC) survival in combination with chemotherapy. However, the majority of patients experience disease progression after first-line treatment and are eligible for second-line approaches. In such a context, antiangiogenic and anti-Epidermal Growth Factor Receptor (EGFR) agents as well as immune checkpoint inhibitors have been approved as second-line options, and RAS and BRAF mutations and microsatellite status represent the molecular drivers that guide therapeutic choices. Patients harboring K- and N-RAS mutations are not eligible for anti-EGFR treatments, and bevacizumab is the only antiangiogenic agent that improves survival in combination with chemotherapy in first-line, regardless of RAS mutational status. Thus, the choice of an appropriate therapy after the progression to a bevacizumab or an EGFR-based first-line treatment should be evaluated according to the patient and disease characteristics and treatment aims. The continuation of bevacizumab beyond progression or its substitution with another anti-angiogenic agents has been shown to increase survival, whereas anti-EGFR monoclonals represent an option in RAS wild-type patients. In addition, specific molecular subgroups, such as BRAF-mutated and Microsatellite Instability-High (MSI-H) mCRCs represent aggressive malignancies that are poorly responsive to standard therapies and deserve targeted approaches. This review provides a critical overview about the state of the art in mCRC second-line treatment and discusses sequential strategies according to key molecular biomarkers.

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