Observational cohort study of first-line bevacizumab with oxaliplatin or irinotecan and fluoropyrimidines in metastatic colorectal cancer: HGCSG0802—Analysis of early tumor shrinkage (ETS).

2016 ◽  
Vol 34 (4_suppl) ◽  
pp. 753-753 ◽  
Author(s):  
Satoshi Yuki ◽  
Hiroshi Nakatsumi ◽  
Kentaro Sawada ◽  
Takashi Kato ◽  
Takashi Meguro ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Multivariate Analysis ◽  
Metastatic Colorectal Cancer ◽  
Univariate Analysis ◽  
First Line ◽  
Factors Associated ◽  
Early Tumor Shrinkage ◽  
Significant Difference ◽  
Early Tumor ◽  
Line Chemotherapy

753 Background: It was reported that early tumor shrinkage (ETS) was associated with better overall survival (OS) in patients (pts) with metastatic colorectal cancer (mCRC) receiving first line chemotherapy. We investigated association of ETS with progression-free survival (PFS) and OS in pts with mCRC treated with first-line bevacizumab (BV)-based chemotherapy (HGCSG0802). Methods: The objective of HGCSG0802 was to evaluate PFS, OS, response rate (RR), safety and so on. The key eligibility criteria were evaluable lesions, older than 20 years old, ECOG PS 0-2. This analysis evaluated the association of ETS at 8 weeks from the start of chemotherapy with pts characteristics, PFS and OS. To identify factors associated with ETS, if there were clinical variables with p < 0.2 in univariate analysis, we planned a multivariate analysis using the logistic regression model. To identify predictive and prognostic factors, a multivariate analysis was performed using Cox proportional hazard model with backward elimination for variables with p < 0.2 in univariate analysis. Results: Of 108 pts (the full analysis set), 99 pts were evaluable for ETS. Sixty-eight pts (68.7%) had ETS ≥20%. The pts characteristics between ETS ≥20% (ETS) and <20% (Non-ETS) were well balanced. In univariate analysis to identify factors associated with ETS, there were no clinical variables with p < 0.2. The median PFS and OS were 7.3/18.3 months in Non-ETS versus 10.0/25.2 months in ETS (HR 0.529; p=0.006 and HR 0.627; p=0.107). In multivariate analysis for PFS and OS, although there was no significant difference between ETS and Non-ETS for OS (HR 0.709; p=0.186), there was significant difference for PFS (HR 0.524; p=0.006). Conclusions: ETS was observed in 68.7% (68/99) and non-ETS in 31.3% (31/99) of patients with metastatic colorectal cancer received bevacizumab combined first line chemotherapy. In univariate analysis, it could not identify any factors associated with ETS. In the results of multivariate analysis, ETS showed an independent predictive impact, but not prognostic impact. Clinical trial information: UMIN000018935.

Early tumor shrinkage indicates a favorable response to bevacizumab-based first-line chemotherapy for metastatic colorectal cancer

2017 ◽  
Vol 28 (10) ◽  
pp. 1166-1173 ◽  
Author(s):  
Mamoru Ito ◽  
Hitoshi Kusaba ◽  
Satomi Mukaide ◽  
Junji Kishimoto ◽  
Hozumi Shimokawa ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Tumor Shrinkage ◽  
First Line ◽  
Early Tumor Shrinkage ◽  
Early Tumor ◽  
Line Chemotherapy

scholarly journals Early tumor shrinkage in metastatic colorectal cancer: Retrospective analysis from an irinotecan-based randomized first-line trial

2013 ◽  
Vol 104 (6) ◽  
pp. 718-724 ◽  
Author(s):  
Clemens Giessen ◽  
Ruediger P. Laubender ◽  
Ludwig Fischer von Weikersthal ◽  
Andreas Schalhorn ◽  
Dominik P. Modest ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Retrospective Analysis ◽  
Tumor Shrinkage ◽  
First Line ◽  
Early Tumor Shrinkage ◽  
Early Tumor

Polymorphism of the chemokine CXCR4 to predict treatment benefit of first-line bevacizumab-based chemotherapy in patients with metastatic colorectal cancer.

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 635-635
Author(s):  
Satoshi Matsusaka ◽  
Fotios Loupakis ◽  
Wu Zhang ◽  
Shu Cao ◽  
Dongyun Yang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Clinical Outcome ◽  
Metastatic Colorectal Cancer ◽  
Tumor Cells ◽  
Direct Sequencing ◽  
Univariate Analysis ◽  
Candidate Snps ◽  
First Line ◽  
Significant Difference

635 Background: The chemokine receptor CXCR4 and its ligand CXCL12 promote angiogenesis and the migration of tumor cells into the metastatic sites in many cancers. CXCR4 expression on tumor cells is upregulated by hypoxia and angiogenic factors, such as vascular endothelial growth factor. Therefore, we analyzed the association between CXCR4/CXCL12 polymorphisms and prognosis in metastatic colorectal cancer (mCRC) patients underwent bevacizumab-based chemotherapy. Methods: This study included 144 Japanese patients (pts) for evaluation set and 424 patients from two clinical trials (204 of TRIBE arm A and 220 of PROVETTA) for validation set, with mCRC treated with bevacizumab-based chemotherapy as first line. A total of 144 Japanese pts with (male/female; 81/63, median age 61 years, median follow-up 4.2 years) and 424 pts (male/female; 252/172, median age 62 years; median follow-up time; 2.8 years) were enrolled in a pharmacogenomics translational study. Genomic DNA was extracted from the pts’ blood or tissue. One CXCR4 single nucleotide polymorphisms (SNP) (rs2228014) and two CXCL12 SNPs (rs1801157, rs3740085) were analyzed by PCR-based direct sequencing. All candidate SNPs were analyzed for association with the clinical outcome. Results: In univariate analysis, CXCR4 rs2228014 showed a significant difference in PFS [(G/G 15.3 months, any A allele 13.7 months, HR (95% CI) 1.64 (1.01-2.68), p=0.036)]. After multivariate analysis, CXCR4 rs2228014 remained to be a significant for PFS [HR (95% CI) 1.67 (1.01-2.78), p =0.046]. However, this polymorphism was not associated with tumor response and survival. In the validation cohort, pts with GG genotype had significantly longer PFS compared to those with any A allele (10.5 vs 9.6 months, HR (95% CI) 1.40 (1.02-1.93), p =0.035). CXCL12 polymorphisms were not associated with the clinical outcome. Conclusions: This study shows for the first time that CXCR4 rs2228014 may serve as a predictive marker in patients with mCRC treated with bevacizumab-based chemotherapy.

Association of early tumor shrinkage with progression-free survival in patients with metastatic colorectal cancer treated with bevacizumab-based chemotherapy: HGCSG0802.

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 749-749
Author(s):  
Hiroshi Nakatsumi ◽  
Satoshi Yuki ◽  
Tetsuhito Muranaka ◽  
Hiraku Fukushima ◽  
Takashi Kato ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Progression Free Survival ◽  
Rank Test ◽  
Tumor Shrinkage ◽  
First Line ◽  
Free Survival ◽  
Log Rank Test ◽  
Early Tumor Shrinkage ◽  
Significant Difference ◽  
Early Tumor

749 Background: It was reported that early tumor shrinkage (ETS) was associated with better overall survival (OS) in patients (pts) with metastatic colorectal cancer (mCRC) receiving cetuximab. We investigated association of ETS with progression free survival (PFS) in pts with unresectable colorectal liver metastases (CLM) from HGCSG0802 observational cohort study in pts with mCRC treated with first-line bevacizumab (BV)-based chemotherapy. Methods: The objective of HGCSG0802 was to evaluate PFS, OS, time to treatment failure (TTF), response rate (RR), safety and so on. The key eligibility criteria were evaluable lesions, older than 20 years old, ECOG PS 0-2. In this analysis, association of ETS at 8 weeks from the start of chemotherapy with pts characteristics, PFS and TTF was evaluated. Pts characteristics were compared using Student-t test, chi-square test and Fisher’s exact test. PFS and TTF were analyzed with Kaplan-Meier method and compared using log-rank test. Univariate analysis for the association of pts characteristics with PFS and TTF was performed using log-rank test, and multivariate analysis was performed using Cox proportional hazards model. Results: Of 108 pts (the full analysis set), 74 pts with CLM were evaluable for ETS. Forty-nine pts (66.2%) had ETS ≥20%. The pts characteristics between ETS ≥20% and <20% were well balanced. The median PFS was 7.3 months in ETS <20% versus 10.0 months in ETS ≥20% (HR 0.55; p=0.025). In multivariate analysis for PFS, there was no significant difference between ETS ≥20% and <20% (HR 0.585; p=0.066). The median TTF (ETS <20% v ≥20%) was 5,1 months vs. 7.7 months (HR 0.46; p=0.003). In multivariate analysis for TTF, there was significant difference between ETS ≥20% and <20% (HR 0.509; p=0.017). Conclusions: In this analysis, ETS ≥20% might be positive predictive marker for PFS and TTF in pts with CLM receiving first-line BV-based chemotherapy.

The impact of early tumor shrinkage on survival in WJOG4407G trial, a randomized phase III trial of mFOLFOX6 plus bevacizumab versus FOLFIRI plus bevacizumab in first-line treatment for metastatic colorectal cancer.

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 679-679 ◽  
Author(s):  
Michitaka Nagase ◽  
Kentaro Yamazaki ◽  
Hiroshi Tamagawa ◽  
Shinya Ueda ◽  
Takao Tamura ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Phase Iii ◽  
Tumor Shrinkage ◽  
Line Treatment ◽  
First Line ◽  
Early Tumor Shrinkage ◽  
Early Tumor ◽  
The Impact ◽  
First Line Treatment

679 Background: Early tumor shrinkage (ETS) has been reported as an important predictor of favorable outcomes in patients with metastatic colorectal cancer (mCRC) receiving first-line chemotherapy. We investigated the impact of ETS on survival in a randomized phase III study (WJOG4407G), which directly compared mFOLFOX6+bevacizumab (Bev) with FOLFIRI+Bev as first-line treatment. Methods: The subjects of this study were patients with measurable lesions whose tumor responses at 8 weeks were evaluated. ETS was defined as 20% or more decrease in the sum of the longest diameters of target lesions (RECIST ver.1.0) at 8 weeks. Progression-free survival (PFS) and overall survival (OS) were compared between patients with ETS and without ETS in each treatment. Results: Of 402 patients enrolled in the WJOG4407G trial, 354 (mFOLFOX6+Bev/FOLFIRI+Bev 175/179) patients were evaluated for this analysis. In this population, response rate, median PFS, and median OS of mFOLFOX+Bev/FOLFIRI+Bev were 65.7/68.2%, 10.7/12.1 months (HR 0.916, 95%CI 0.725-1.157, p=0.281), and 28.9/31.9 months (HR 0.870, 95%CI 0.653-1.159, p=0.272), respectively. One hundred (57.1%)/113 (63.1%) patients in the FOLFOX+Bev/FOLFIRI+Bev groups achieved ETS. No significant difference of the ratio of the patients with ETS between both groups was observed (p=0.099). In the FOLFIRI+Bev group, both PFS and OS were significantly longer in patients with ETS than those without ETS while there were no remarkable differences in the mFOLFOX6+Bev group (see Table). Conclusions: There were substantial differences in PFS and OS between the patients with and without ETS in the FOLFIRI+Bev group, but not in the FOLFOX+Bev group. The impact of ETS on survival is suggested to be different according to chemotherapy regimens. Clinical trial information: UMIN000001396. [Table: see text]

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