Use of VEGF expression to predict for first-line treatment chemotherapy regimen in metastatic colorectal cancer.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e14695-e14695
Author(s):  
Metin Ozkan ◽  
Veli Berk ◽  
Kemal Deniz ◽  
Halit Karaca ◽  
Mevlude Inanc ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Metastatic Colorectal Cancer ◽  
Survival Rates ◽  
First Line ◽  
Vegf Expression ◽  
Treatment Protocols ◽  
Primary Tumors ◽  
Study Results ◽  
Low Expression

e14695 Background: In metastatic colorectal cancer treatment more successful results are achieved by adding anti-angiogenic therapy to the chemotherapy. Over expression of VEGF in colorectal cancer is known to be a poor prognosis factor but its effects on designating the therapy is not clear. In this study, results of the patients receiving FOLFIRI + Bevacizumab or XELOX + Bevacizumab were compared for VEGF expression. Methods: VEGF was assessed immunohistochemically in primary tumors of the 53 metastatic colorectal cancers. Severity and conformity of VEGF expression was evaluated. Results were used to assess the association with the therapy response, progression free survival (PFS) and overall survival (OS). Results: The median age of the patients was 55 (range, 32-79). In combination with bevacizumab 38 patients received FOLFIRI and 15 patients received XELOX. In 30 patients (57%) there was a strong expression of VEGF and in 23 patients (23%) the expression was weak. In the high VEGF expression group, PFS was 11 months in FOLFIRI receiving patients and 8 months in XELOX receiving ones but in low expression group PFS was 8 months in patients receiving either one of the two treatment protocols. In high expression group, PFS in FOLFIRI-bevacizumab combination receiving patients was different and this difference was statistically significant (p=0.009). Overall survival in FOLFIRI receiving patients with high VEGF expression was 26 months and with low VEGF expression it was 16 months (p=0.04). Median OS was not reached in the XELOX receiving patient group. FOLFIRI regime clinical benefit was 58% in high VEGF expression group whilst it was 34% in low expression group. This difference was not statistically significant but it was close to the significance threshold (p=0.06). There was no association between the therapy responses and VEGF expression of the 15 patients who received XELOX. Conclusions: There is no difference in efficacy between the first line chemotherapy regimens of the metastatic colorectal cancer. In this study, in metastatic colorectal patients with over expressed VEGF first line FOLFIRI-bevacizumab combination led to better response and survival rates.

Predictive significance of VEGF and HIF-1α expression in metastatic colorectal cancer patients receiving chemotherapy combined with bevacizumab.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e14672-e14672
Author(s):  
Veli Berk ◽  
Kemal Deniz ◽  
Halit Karaca ◽  
Mevlude Inanc ◽  
Oktay Bozkurt ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Clinical Benefit ◽  
Hypoxia Inducible Factor ◽  
Therapy Response ◽  
Progression Free Survival ◽  
Vegf Expression ◽  
Primary Tumors ◽  
Colorectal Cancer Patients ◽  
Low Expression

e14672 Background: There is no suggested molecular indicator in identifying which patients will benefit from anti-angiogenic treatment in metastatic colorectal cancer. Over expression of vascular endothelial growth factor (VEGF) and Hypoxia Inducible Factor 1-alpha (HIF-1α) are associated with bad prognosis. In this study, VEGF and HIF-1α expression and their clinical significance are studied in tumor tissues of patients with colorectal cancer receiving treatment with bevacizumab. Methods: VEGF and HIF-1α were observed immunohistochemically in primary tumors of 53 patients. The expressions were separated by evaluating low and high of VEGF and HIF-1α expression. We evaluated whether expression of VEGF and HIF-1α can help to predict treatment response, progression free survival (PFS), and overall survival (OS). Results: Fifty-three patients were enrolled in the study. Median age was 55. VEGF was strongly expressed in 30 patients (57%) whilst low expression was observed in 23 of them (43%). When VEGF expression was evaluated in association with therapy response rates; the clinical benefit rate was 38% in the low expression group whereas it was 62% in high expression group. This difference was statistically significant (p=0.01). In the group with strong VEGF expression PFS was 10 months whereas it was 8 months in the low expression group (p=0.009). When evaluated for OS, 26 months versus 15 months was in favor of highly expressed VEGF group (p=0.03). Highly expressed HIF-1α was found in 29 patients (55%), on the other hand low expressed HIF-1α was detected in 24 (%45) patients. For clinical benefit rates, PFS and OS there was no difference between high and low expressed HIF-1α groups. Conclusions: It has been demonstrated that VEGF and HIF-1α expressions are associated with poor prognosis in several tumors, mainly colorectal carcinomas. With the better understanding of carciogenesis and angiogenesis at molecular level, especially VEGF and HIF-1α became target molecules of the therapy. According to results of our study, VEGF expression is a predictive factor in designating the metastatic colorectal cancer treatment.

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

Surrogate End Points for Median Overall Survival in Metastatic Colorectal Cancer: Literature-Based Analysis From 39 Randomized Controlled Trials of First-Line Chemotherapy

2007 ◽  
Vol 25 (29) ◽  
pp. 4562-4568 ◽  
Author(s):  
Patricia A. Tang ◽  
Søren M. Bentzen ◽  
Eric X. Chen ◽  
Lillian L. Siu
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Randomized Controlled Trials ◽  
Metastatic Colorectal Cancer ◽  
Controlled Trials ◽  
First Line ◽  
End Points ◽  
Randomized Controlled ◽  
Hazard Ratios ◽  
Line Chemotherapy

Purpose Our aims were to determine the correlations between progression-free survival (PFS), time to progression (TTP), and response rate (RR) with overall survival (OS) in the first-line treatment of metastatic colorectal cancer (MCRC), and to identify a potential surrogate for OS. Methods Randomized trials of first-line chemotherapy in MCRC were identified, and statistical analyses were undertaken to evaluate the correlations between the end points. Results Thirty-nine randomized controlled trials were identified containing a total of 87 treatment arms. Among trials, the nonparametric Spearman rank correlation coefficient (rs) between differences (Δ) in surrogate end points (ΔPFS, ΔTTP, and ΔRR) and ΔOS were 0.74 (95% CI, 0.47 to 0.88), 0.52 (95% CI, 0.004 to 0.81), 0.39 (95% CI, 0.08 to 0.63), respectively. The rs for ΔPFS was not significantly different from the rs ΔTTP (P = .28). Linear regression analysis was performed using hazard ratios for PFS and OS. There was a strong relationship between hazard ratios for PFS and OS; the slope of the regression line was 0.54 ± 0.10, indicating that a novel therapy producing a 10% risk reduction for PFS will yield an estimated 5.4% ± 1% risk reduction for OS. Conclusion In first-line chemotherapy trials for MCRC, improvements in PFS are strongly associated with improvements in OS. In this patient population, PFS may be an appropriate surrogate for OS. As a clinical end point, PFS offers increased statistical power at a given time of analysis and a significant lead time advantage compared with OS.

Metastatic Colorectal Cancer Treatment to progression or Not?

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 13511-13511
Author(s):  
B. Melosky ◽  
C. Lohrisch ◽  
C. Kollmansberger ◽  
S. Gill ◽  
H. Kennecke ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Metastatic Colorectal Cancer ◽  
Hazard Ratio ◽  
Second Line ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy ◽  
Number Of Cycles ◽  
Line Chemotherapy

13511 Background: Treatment until progression or planned interruption of first line chemotherapy is common in the therapy for metastatic colorectal cancer and are upon the discretion of the oncologist. A retrospective analysis was performed to determine the impact of these differing therapeutic strategies on overall survival. Methods: Eligible patients were treated between 2002 to 2004 in British Columbia. All patients received chemotherapy with both FOLFOX and FOLFIRI, either first or second line. Records were retrospectively reviewed for treatment interruption, efficacy and toxicity. Overall survival was the primary endpoint. Results: 101 patients were identified. Twenty-three patients who progressed before receiving 8 cycles of chemotherapy and 9 patients who stopped their chemotherapy due to toxicity were excluded. The remaining patients were analyzed for survival. Twenty-three patients were treated to progression of whom 6 received first line FOLFIRI and 17 received first line FOLFOX. The mean number of cycles of first line therapy was was 11.5. Forty six patients received a planned break. Of these, 21pateints received first line FOLFIRI and 25 patients received first line FOLFOX. Mean number of cycles of first line therapy was 9.7. Median survival of patients treated to progression was 16 months compared to 22 months for patients with planned break of therapy (p=0.003). The Hazard ratio was 2.3 (p=0.01) in favor of patients who had a planned break. Uni-variate and multivariate analysis showed no significance of sex, age, site (colon versus rectal), sequence and ECOG status as predictive factors. Conclusion: In this study, patients who were treated until progression with first line chemotherapy with either FOLFOX or FOLFIRI had an inferior survival. Possible explanations for the detrimental hazard ratio for patients treated to progression are decreasing reserve for second line therapy when first line therapy is prolonged and increasing resistance to 5-FU based therapy with prolonged exposure. As this is a retrospective, observational study, other variables not captured by the modeled covariates that may have influenced results. This data suggests that treating to best response and then allowing a break does not detrimentally affect survival. No significant financial relationships to disclose.

Effect of the addition of bevacizumab to first-line FOLFOX on efficacy, including response rate, progression-free survival, and overall survival, in patients with metastatic colorectal cancer.

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 588-588
Author(s):  
M. Suenaga ◽  
N. Mizunuma ◽  
S. Matsusaka ◽  
E. Shinozaki ◽  
M. Ogura ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Metastatic Colorectal Cancer ◽  
Survival Benefit ◽  
Response Rate ◽  
Progression Free Survival ◽  
Line Treatment ◽  
First Line ◽  
Free Survival ◽  
First Line Treatment

588 Background: Bevacizumab (BV) is a recombinant, humanized monoclonal antibody against vascular endothelial growth factor. Used in combination with chemotherapy, BV has been shown to improve survival in both first- and second-line treatment for metastatic colorectal cancer (mCRC). However, it was reported that addition of BV to FOLFOX conferred only little survival benefit (Saltz et al. JCO2008). The aim of this study was to assess the efficacy of addition of BV to FOLFOX in first-line treatment for patients with mCRC. Methods: Bevacizumab was approved for mCRC in July 2007 in Japan. This study was conducted at a single institution and comprised 217 consecutive patients receiving first-line treatment for mCRC between 2005 and 2009. The primary objective was to compare survival benefit in patients treated with FOLFOX4 (FF) between 2005 and 2007 with that in patients receiving FOLFOX4+BV 5 mg/kg (FF+BV) between 2007 and 2009. Results: Total number of patients in the FF and FF+BV groups was 132 and 85, respectively. Characteristics of patients were as follows (FF vs. FF+B): median age, 62 yrs (range 28-76 yrs) vs. 60 yrs (range16-74 yrs); ECOG PS0, 98.8% vs. 81.8%; and median follow-up time, 20.8 months vs. 24.4 months. Median progression-free survival (PFS) in the FF and FF+BV groups was 10 months (95% CI, 8.7-11.3) and 17 months (95% CI, 10.2-14.1), while median overall survival (OS) was 21 months (95% CI, 17.9-24.1) and not reached, respectively. Response rate was 46% (95% CI, 37- 54) in FF, and 62% (95% CI, 51-73) in FF+BV. Addition of BV to FOLFOX4 significantly improved PFS (p=0.002) and OS (p<0.001). Conclusions: The additive effect of BV for first-line FOLFOX was reconfirmed. These data indicate potential survival benefits from the addition of BV to FOLFOX in first-line treatment of mCRC. In addition, PFS may be a sensitive indicator of outcome prior to post-treatment. No significant financial relationships to disclose.

The efficacy of first-line IRIS with or without bevacizumab in patients with metastatic colorectal cancer: Analysis of two phase II studies.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e14604-e14604
Author(s):  
Satoshi Yuki ◽  
Hiraku Fukushima ◽  
Toraji Amano ◽  
Michio Nakamura ◽  
Mineo Kudo ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Phase Ii ◽  
Performance Status ◽  
Safety Data ◽  
Hazard Ratio ◽  
First Line ◽  
Two Phase ◽  
Phase Ii Studies ◽  
Study Results

e14604 Background: The safety and efficacy of first-line IRIS (S-1 in combination with irinotecan; Komatsu Y, et al. Oncology, 2011) and IRIS/Bev (IRIS in combination with bevacizumab (Bev); Komatsu Y, et al. Acta Oncol, 2012/Yuki S, et al. 2013 ASCO-GI) have been evaluated in patients with metastatic colorectal cancer (mCRC). This time, no randomized studies comparing these regimens have been performed. This retrospective analysis compared efficacy and safety data for the two regimens from separate phase II studies performed at Hokkaido Gastrointestinal Cancer Study Group (HGCSG). Methods: Patients with histologically confirmed unresectable metastatic or recurrent CRC and received no prior chemotherapy were enrolled. In the first trial, patients received irinotecan 100 mg/m2 on day 1,15 and oral S-1 40 mg/m2 twice daily on days 1-14 every 4 weeks (IRIS study: HGCSG0302). In the second trial, patients received the same regimen plus Bev 5 mg/kg on day 1,15 (IRIS/Bev study). Results: A total of 40 and 52 patients were enrolled the IRIS and IRIS/Bev studies, respectively. Patient characteristics were generally similar in both groups, whereas there were more cases of good performance status and less number of metastatic organ in IRIS/Bev group. The median overall survival was 39.6 months in IRIS/Bev, as compared with 23.4 months in IRIS, corresponding to a hazard ratio for death of 0.418 (p<0.001). The median progression-free survival was 17.0 months in IRIS/Bev, as compared with 8.6 months in IRIS (hazard ratio for disease progression, 0.418; p<0.001); the corresponding response rate were 63.5 percent and 52.5 percent (p=0.393).In a multivariate analysis of PFS and OS, IRIS/Bev (n=52) was significantly associated with longer PFS and OS compared with IRIS alone (n=40). Conclusions: In this retrospective comparison of two studies, the addition of Bev to IRIS appeared to improve outcome compared with IRIS alone in the first-line treatment of patients with mCRC.

scholarly journals MONARCC: a randomised phase II study of panitumumab monotherapy and panitumumab plus 5-fluorouracil as first-line therapy for RAS and BRAF wildtype metastatic colorectal cancer: a study by the Australasian Gastrointestinal Trials Group (AGITG)

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Ho Wai Derrick Siu ◽  
Niall Tebbutt ◽  
Lorraine Chantrill ◽  
Chris Karapetis ◽  
Christopher Steer ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Colorectal Cancer ◽  
Overall Survival ◽  
Metastatic Colorectal Cancer ◽  
Phase Ii ◽  
Tumour Response ◽  
Trial Registration ◽  
First Line ◽  
The Impact

Abstract Background Doublet chemotherapy in combination with a biologic agent has been a standard of care in patients with metastatic colorectal cancer for over a decade. The evidence for a “lighter” treatment approach is limited to mono-chemotherapy plus bevacizumab in the RAS unselected population. Anti-EGFR antibodies have activity as monotherapy or in combination with chemotherapy in RAS wildtype metastatic colorectal cancer; however their role in first-line treatment in combination with 5-fluorouracil monotherapy or when given alone has not been well studied. MONARCC aims to investigate this approach in an elderly population. Methods/design MONARCC is a prospective, open-label, multicentre, non-comparative randomised phase II trial. Eligible patients aged ≥70 with unresectable metastatic, untreated, RAS/BRAF wildtype metastatic colorectal cancer will be randomised 1:1 to receive panitumumab alone or panitumumab plus infusional 5-fluorouracil. RAS and BRAF analyses will be performed in local laboratories. Comprehensive Health Assessment and Limited Health Assessments will be performed at baseline and at 16 weeks, respectively, to assess frailty. The Patient Symptom Questionnaire and Overall Treatment Utility are to be undertaken at different timepoints to assess the impact of treatment-related toxicities and quality of life. Treatment will be delivered every 2 weeks until disease progression, unacceptable toxicity (as determined by treating clinician or patient), delay of treatment of more than 6 weeks, or withdrawal of consent. The primary end point is 6-month progression-free survival in both arms. Secondary end points include overall survival, time to treatment failure, objective tumour response rate as defined by RECIST v1.1 and safety (adverse events). Tertiary and correlative endpoints include the feasibility and utility of a comprehensive geriatric assessment, quality of life and biological substudies. Discussion MONARCC investigates the activity and tolerability of first-line panitumumab-based treatments with a view to expand on current treatment options while maximising progression-free and overall survival and quality of life in molecularly selected elderly patients with metastatic colorectal cancer. Trial registration Australia New Zealand Clinical Trials Registry: ACTRN12618000233224, prospectively registered 14 February 2018.

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