Extended RAS analysis and subsequent anti-EGFR and anti-VEGF treatment (tx) in PEAK: A first-line phase 2 study of FOLFOX6 + panitumumab (pmab) or bevacizumab (bev) in metastatic colorectal cancer (mCRC).

2014 ◽  
Vol 32 (15_suppl) ◽  
pp. 3629-3629 ◽  
Author(s):  
Fernando Rivera ◽  
Lee Steven Schwartzberg ◽  
Meinolf Karthaus ◽  
Gianpiero Fasola ◽  
Jean-Luc Canon ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Phase 2 ◽  
First Line ◽  
Anti Vegf ◽  
Phase 2 Study

Phase 2 study of second-line FOLFIRI-aflibercept in prospectively stratified, RAS wild type, anti-EGFR resistant, metastatic colorectal cancer patients: The DISTINCTIVE trial.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e15503-e15503
Author(s):  
Eleonora Lai ◽  
Fotios Loupakis ◽  
Pina Ziranu ◽  
Giuseppe Aprile ◽  
Alberto Zaniboni ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Interim Analysis ◽  
Angiogenic Factors ◽  
Rank Test ◽  
Second Line ◽  
Phase 2 ◽  
Wild Type ◽  
First Line ◽  
Phase 2 Study

e15503 Background: Data on anti-angiogenic second line treatment in RAS wild type (wt) metastatic colorectal cancer (mCRC) patients (pts) progressing after first-line anti-EGFR drug are lacking and no validated biomarkers are available. We present the pre-planned interim analysis of the DISTINCTIVE trial (NCT04252456), a biologically enriched, prospectively stratified phase 2 study assessing the aflibercept use in this setting. Methods: RAS wt mCRC pts progressing after first line oxaliplatin-based + anti-EGFR therapy and candidates for second-line FOLFIRI/aflibercept are eligible for the DISTINCTIVE trial. Pts are prospectively allocated to a favorable (F) or unfavorable (U) prognostic group, according to Elisa-assessed baseline (BL) VEGFR2 plasma levels (PL). Other circulating angiogenic factors are evaluated at BL, first tumor assessment (TA1) and disease progression (PD). Primary endpoint is overall survival (OS) according to VEGFR2 levels. Secondary endpoints are OS, progression free survival (PFS), response rate, safety and angiogenic factors levels. Statistical analysis is performed with MedCalc (survival distribution: Kaplan-Meier; survival comparison: log-rank test; multivariate analysis: logistic regression). Sample size: 151 pts (one-sided test, α: 0.1, β: 0.2). Results: From 04/2018 to 06/2020, 73 pts were enrolled. Complete data from 44 pts were available for interim analysis. 33 pts (75%) achieved DCR (26 pts/59% SD, 7 pts/16% PR). Globally, median OS was 11.9 months (m) (95%CI 10 – 14.2). 24 (54.5%) pts were prospectively assigned to F group (VEGFR2 PL > 4 ng/ml) and 20 (45.5%) to U group (VEGFR2 PL ≤4 ng/ml). OS in F group was 13.1 m (95%CI 9.6 – 14.2) vs 11.9 m (95%CI 6.8 – 11.9) in U group (HR 0.76 p = 0.6218). PFS was 9.8 m [95%CI 5.7 – 24.2] in F group vs 4.2 m [95%CI 2.5 – 14.2] in U group (HR 0.41 p = 0.0105). We also found preliminary correlation with PD as shown in table. Conclusions: Interim analysis showed high activity of FOLFIRI/aflibercept in RAS WT anti-EGFR pretreated mCRC pts. VEGFR2 showed promising ability to predict aflibercept efficacy. Our data on circulating angiogenic biomarkers are likely to further compose the landscape of anti-angiogenic activity in mCRC pts. Clinical trial information: NCT04252456. [Table: see text]

scholarly journals Axitinib and/or bevacizumab with modified FOLFOX-6 as first-line therapy for metastatic colorectal cancer: A randomized phase 2 study

Cancer ◽  
2013 ◽  
Vol 119 (14) ◽  
pp. 2555-2563 ◽  
Author(s):  
Jeffrey R. Infante ◽  
Tony R. Reid ◽  
Allen L. Cohn ◽  
William J. Edenfield ◽  
Terrence P. Cescon ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Phase 2 ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy ◽  
Phase 2 Study ◽  
Randomized Phase 2

scholarly journals A double-blind, randomized, placebo-controlled, phase 2 study of maintenance enzastaurin with 5-fluorouracil/leucovorin plus bevacizumab after first-line therapy for metastatic colorectal cancer

Cancer ◽  
2011 ◽  
Vol 118 (17) ◽  
pp. 4132-4138 ◽  
Author(s):  
Robert A. Wolff ◽  
Martin Fuchs ◽  
Maria Di Bartolomeo ◽  
Anwar M. Hossain ◽  
Clemens Stoffregen ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Phase 2 ◽  
First Line ◽  
Double Blind ◽  
First Line Therapy ◽  
Line Therapy ◽  
Phase 2 Study

scholarly journals Comparison of irinotecan and oxaliplatin as the first-line therapies for metastatic colorectal cancer: a meta-analysis

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Sadayuki Kawai ◽  
Nozomi Takeshima ◽  
Yu Hayasaka ◽  
Akifumi Notsu ◽  
Mutsumi Yamazaki ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Meta Analysis ◽  
Controlled Trials ◽  
Significant Heterogeneity ◽  
Cochrane Central Register ◽  
First Line ◽  
Anti Vegf ◽  
Significant Difference ◽  
High Incidence

Abstract Background Irinotecan (IRI) and oxaliplatin (Ox) are standard therapeutic agents of the first-line treatments for metastatic colorectal cancer (mCRC). Previous meta-analyses of randomized controlled trials (RCTs) showed that treatment with Ox-based compared with IRI-based regimens was associated with better overall survival (OS). However, these reports did not include trials of molecular targeting agents and did not take methods for the administration of concomitant drugs, such as bolus or continuous infusion of 5-fluorouracil, into account. A systematic literature review was performed to compare the efficacy and toxicity profiles between IRI- and Ox-based regimens as the first-line treatments for mCRC. Methods This meta-analysis used data from the Cochrane Central Register of Controlled Trials, PubMed, and SCOPUS. The primary endpoint was OS, and the secondary endpoints were progression-free survival (PFS), objective response rate (ORR), and adverse events (AEs). Results Nineteen trials involving 4571 patients were included in the analysis. No statistically significant difference was observed between the two groups in terms of OS, PFS, and ORR. There was no significant heterogeneity. Regarding ≥ grade 3 AEs, IRI-based regimens were associated with a high incidence of leukopenia, febrile neutropenia, and diarrhea. Moreover, there was a high incidence of thrombocytopenia and peripheral sensory neuropathy in patients who received Ox-based regimens. In a subgroup analysis, IRI combined with bevacizumab was correlated with a better PFS (HR = 0.90, 95% CI = 0.82–0.98, P = 0.02), but not with OS (pooled HR = 0.91, 95% CI = 0.80–1.03, P = 0.15). Conclusion Although the safety profiles of IRI- and Ox-based regimens varied, their efficacy did not significantly differ. The combination of anti-VEGF antibody and IRI was associated with better PFS compared with anti-VEGF antibody and Ox. Both regimens could be used as the first-line treatments for mCRC with consideration of the patients’ condition or toxicity profiles.

scholarly journals Subsequent anti-VEGF therapy after first-line anti-EGFR therapy improved overall survival of patients with metastatic colorectal cancer

2018 ◽  
Vol Volume 11 ◽  
pp. 465-471 ◽  
Author(s):  
Tianzhu Qiu ◽  
Wensen Chen ◽  
Ping Li ◽  
Jing Sun ◽  
Yanhong Gu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Metastatic Colorectal Cancer ◽  
First Line ◽  
Anti Vegf

Exploratory biomarker findings from cohort 2 of MODUL: An adaptable, phase 2, signal-seeking trial of fluoropyrimidine + bevacizumab ± atezolizumab maintenance therapy for BRAFwt metastatic colorectal cancer.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 3570-3570
Author(s):  
Josep Tabernero ◽  
Axel Grothey ◽  
Dirk Arnold ◽  
Michel Ducreux ◽  
Peter J. O'Dwyer ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Maintenance Treatment ◽  
Predictive Biomarkers ◽  
Experimental Treatment ◽  
Progression Free Survival ◽  
Phase 2 ◽  
First Line ◽  
Tissue Samples ◽  
First Line Therapy

3570 Background: MODUL is an adaptable, phase 2, signal-seeking trial testing novel agents as first-line therapy for predefined subgroups of patients with metastatic colorectal cancer (mCRC). Previously reported findings demonstrated that adding atezolizumab to fluoropyrimidine (FP)/bevacizumab as first-line maintenance treatment after induction with FOLFOX + bevacizumab did not improve efficacy outcomes in BRAFwt mCRC. Given these efficacy results, exploratory assessments on tumour samples were conducted to provide insights into factors that might affect efficacy of maintenance treatment and provide guidance on appropriate therapeutic strategies for BRAFwt mCRC. Methods: In patients with BRAFwt tumours (Cohort 2), experimental treatment was FP/bevacizumab + atezolizumab. Primary efficacy endpoint: progression-free survival (PFS). Overall survival (OS) was a secondary endpoint. Archival tissue samples from 104 patients were analysed by immunohistochemistry (IHC) at HistoGeneX (PD-L1; CD8/GrB/FoxP3). SP142 antibody was used for PD-L1 IHC analysis, which evaluated PD-L1low (IC 0–1) vs PD-L1high (IC > 1) in correlation with PFS and OS in the control and experimental arms. CD8/GrB/FoxP3 triplex staining was also performed to evaluate potential correlations with efficacy. Results: 445 patients with BRAFwt mCRC were randomised (2:1 ratio) to maintenance treatment in Cohort 2. Archival samples from 104 patients were analysed: FP/bevacizumab + atezolizumab (n = 82); FP/bevacizumab (n = 22). The biomarker evaluable population (BEP) for PD-L1 was n = 81 for FP/bevacizumab + atezolizumab [PD-L1low n = 35 (43%); PD-L1high n = 46 (57%)] and n = 22 for FP/bevacizumab [PD-L1low n = 16 (72%); PD-L1high n = 6 (28%)]. The BEP for CD8/GrB was n = 50 for FP/bevacizumab + atezolizumab and n = 16 for FP/bevacizumab. No difference in PFS or OS was observed in the FP/bevacizumab + atezolizumab vs FP/bevacizumab arms for PD-L1high [PFS: HR = 1.5 (95% CI 0.45−4.8), p = 0.51; OS: HR = 1.3 (95% CI 0.38−4.1), p = 0.71] or PD-L1low [PFS: HR = 0.92 (95% CI 0.47−1.8), p = 0.81; OS: HR = 0.78 (95% CI 0.4−1.5), p = 0.48]. Similar results were observed with CD8/GrBhigh [PFS: HR = 0.73 (95% CI 0.27−2.0), p = 0.55; OS: HR = 0.66 (95% CI 0.24−1.8), p = 0.44], CD8/GrBlow [PFS: HR = 1.0 (95% CI 0.42–2.5), p = 0.96; OS: HR = 0.73 (95% CI 0.3–1.8), p = 0.5], FoxP3high [PFS: HR = 0.97 (95% CI 0.37−2.5), p = 0.95; OS: HR = 0.95 (95% CI 0.36−2.5), p = 0.91] and FoxP3low [PFS: HR = 0.73 (95% CI 0.29−1.9), p = 0.53; OS: HR = 0.5 (95% CI 0.19−1.3), p = 0.18]. Conclusions: These findings suggest that PD-L1, CD8/GrB and FoxP3 might not be predictive biomarkers in BRAFwt mCRC. Further analyses are needed to further evaluate potential predictive and prognostic factors of response in this setting. Clinical trial information: NCT02291289.

Sign in / Sign up

Export Citation Format

Share Document