Limits...
A plasma cytokine and angiogenic factor (CAF) analysis for selection of bevacizumab therapy in patients with metastatic colorectal cancer.

Bai L, Wang F, Zhang DS, Li C, Jin Y, Wang DS, Chen DL, Qiu MZ, Luo HY, Wang ZQ, Li YH, Wang FH, Xu RH - Sci Rep (2015)

Bottom Line: Patients with lower pretreatment levels of hepatocyte growth factor (HGF) or VEGF-A(121) gain much more benefit from bevacizumab treatment as measured by progression-free survival (PFS) and overall survival (OS), while angiopoietin-like 4 (ANGPTL4) levels negatively correlated with PFS and response rate following bevacizumab (all adjusted interaction P < 0.05).Signature-negative patients showed impaired survival following bevacizumab treatment (PFS, 7.3 vs 7.0 months; hazard ratio [HR] 1.03; OS, 29.9 vs 21.1 months, HR 1.33) compared with signature-positive patients (PFS, 6.5 vs 11.9 months, HR 0.52; OS, 28.0 vs 55.3 months, HR 0.67).These promising results warrant further prospective studies.

View Article: PubMed Central - PubMed

Affiliation: Department of Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong 510060, P. R. China.

ABSTRACT
This study intends to identify biomarkers that could refine the selection of patients with metastatic colorectal cancer (mCRC) for bevacizumab treatment. Pretreatment 36 plasma cytokines and angiogenic factors (CAFs) were first measured by protein microarray analysis in patients who received first-line bevacizumab-containing therapies (discovery cohort, n = 64), and further evaluated by enzyme-linked immunosorbent assay in patients treated on regimens with or without bevacizumab (validation cohort, n = 186). Factor levels were correlated with clinical outcomes, predictive values were assessed using a treatment by marker interaction term in the Cox model. Patients with lower pretreatment levels of hepatocyte growth factor (HGF) or VEGF-A(121) gain much more benefit from bevacizumab treatment as measured by progression-free survival (PFS) and overall survival (OS), while angiopoietin-like 4 (ANGPTL4) levels negatively correlated with PFS and response rate following bevacizumab (all adjusted interaction P < 0.05). A baseline CAF signature combining these three markers has greater predictive ability than individual markers. Signature-negative patients showed impaired survival following bevacizumab treatment (PFS, 7.3 vs 7.0 months; hazard ratio [HR] 1.03; OS, 29.9 vs 21.1 months, HR 1.33) compared with signature-positive patients (PFS, 6.5 vs 11.9 months, HR 0.52; OS, 28.0 vs 55.3 months, HR 0.67). These promising results warrant further prospective studies.

No MeSH data available.


Related in: MedlinePlus

PFS (A) and OS (B) Kaplan–Meier plots of patients stratified by treatment arm based on three-marker signature index (positive versus negative).The signature negative indicates CAF Index = 0 or 1; the signature positive indicates CAF Index = 2 or 3. A score of +1 was assigned for candidate marker (ANGPTL4, HGF or VEGF121) concentrations below the corresponding cut-off or 0 for those above the cut-off. Then the score of each marker was added for each patient. Bev, bevacizumab; Chemo, chemotherapy.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4664961&req=5

f5: PFS (A) and OS (B) Kaplan–Meier plots of patients stratified by treatment arm based on three-marker signature index (positive versus negative).The signature negative indicates CAF Index = 0 or 1; the signature positive indicates CAF Index = 2 or 3. A score of +1 was assigned for candidate marker (ANGPTL4, HGF or VEGF121) concentrations below the corresponding cut-off or 0 for those above the cut-off. Then the score of each marker was added for each patient. Bev, bevacizumab; Chemo, chemotherapy.

Mentions: To create a “CAF index” from these candidate markers (ANGPTL4, HGF or VEGF121), a score of +1 was assigned for markers concentrations below the corresponding cut-off or 0 for those above the cut-off. Then the index for each patient was calculated by adding the score for each marker so that the final CAF index ranged from 0 to 3. We selected a CAF index value of 1 as the cut-off because the resulting groups were the most balanced (Half patients with CAF Index = 0 or 1 [signature negative] and half with CAF Index = 2 or 3 [signature positive]). Signature negative individuals showed no improvement in PFS following bevacizumab treatment (7.3 vs 7.0 months; HR, 1.03) compared to signature positive individuals (6.5 vs 11.9 months; HR, 0.52). With the addition of bevacizumab, median OS was only prolonged in patients with positive signature (28.0 vs 55.3 months; HR 0.67), while signature negative patients had an impaired OS following bevacizumab (29.9 vs 21.1; HR 1.33) (Fig. 5). The interaction between the CAF signature and the effect of bevacizumab was highly significant (interaction P = 0.001 for PFS; interaction P = 0.011 for OS).


A plasma cytokine and angiogenic factor (CAF) analysis for selection of bevacizumab therapy in patients with metastatic colorectal cancer.

Bai L, Wang F, Zhang DS, Li C, Jin Y, Wang DS, Chen DL, Qiu MZ, Luo HY, Wang ZQ, Li YH, Wang FH, Xu RH - Sci Rep (2015)

PFS (A) and OS (B) Kaplan–Meier plots of patients stratified by treatment arm based on three-marker signature index (positive versus negative).The signature negative indicates CAF Index = 0 or 1; the signature positive indicates CAF Index = 2 or 3. A score of +1 was assigned for candidate marker (ANGPTL4, HGF or VEGF121) concentrations below the corresponding cut-off or 0 for those above the cut-off. Then the score of each marker was added for each patient. Bev, bevacizumab; Chemo, chemotherapy.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4664961&req=5

f5: PFS (A) and OS (B) Kaplan–Meier plots of patients stratified by treatment arm based on three-marker signature index (positive versus negative).The signature negative indicates CAF Index = 0 or 1; the signature positive indicates CAF Index = 2 or 3. A score of +1 was assigned for candidate marker (ANGPTL4, HGF or VEGF121) concentrations below the corresponding cut-off or 0 for those above the cut-off. Then the score of each marker was added for each patient. Bev, bevacizumab; Chemo, chemotherapy.
Mentions: To create a “CAF index” from these candidate markers (ANGPTL4, HGF or VEGF121), a score of +1 was assigned for markers concentrations below the corresponding cut-off or 0 for those above the cut-off. Then the index for each patient was calculated by adding the score for each marker so that the final CAF index ranged from 0 to 3. We selected a CAF index value of 1 as the cut-off because the resulting groups were the most balanced (Half patients with CAF Index = 0 or 1 [signature negative] and half with CAF Index = 2 or 3 [signature positive]). Signature negative individuals showed no improvement in PFS following bevacizumab treatment (7.3 vs 7.0 months; HR, 1.03) compared to signature positive individuals (6.5 vs 11.9 months; HR, 0.52). With the addition of bevacizumab, median OS was only prolonged in patients with positive signature (28.0 vs 55.3 months; HR 0.67), while signature negative patients had an impaired OS following bevacizumab (29.9 vs 21.1; HR 1.33) (Fig. 5). The interaction between the CAF signature and the effect of bevacizumab was highly significant (interaction P = 0.001 for PFS; interaction P = 0.011 for OS).

Bottom Line: Patients with lower pretreatment levels of hepatocyte growth factor (HGF) or VEGF-A(121) gain much more benefit from bevacizumab treatment as measured by progression-free survival (PFS) and overall survival (OS), while angiopoietin-like 4 (ANGPTL4) levels negatively correlated with PFS and response rate following bevacizumab (all adjusted interaction P < 0.05).Signature-negative patients showed impaired survival following bevacizumab treatment (PFS, 7.3 vs 7.0 months; hazard ratio [HR] 1.03; OS, 29.9 vs 21.1 months, HR 1.33) compared with signature-positive patients (PFS, 6.5 vs 11.9 months, HR 0.52; OS, 28.0 vs 55.3 months, HR 0.67).These promising results warrant further prospective studies.

View Article: PubMed Central - PubMed

Affiliation: Department of Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong 510060, P. R. China.

ABSTRACT
This study intends to identify biomarkers that could refine the selection of patients with metastatic colorectal cancer (mCRC) for bevacizumab treatment. Pretreatment 36 plasma cytokines and angiogenic factors (CAFs) were first measured by protein microarray analysis in patients who received first-line bevacizumab-containing therapies (discovery cohort, n = 64), and further evaluated by enzyme-linked immunosorbent assay in patients treated on regimens with or without bevacizumab (validation cohort, n = 186). Factor levels were correlated with clinical outcomes, predictive values were assessed using a treatment by marker interaction term in the Cox model. Patients with lower pretreatment levels of hepatocyte growth factor (HGF) or VEGF-A(121) gain much more benefit from bevacizumab treatment as measured by progression-free survival (PFS) and overall survival (OS), while angiopoietin-like 4 (ANGPTL4) levels negatively correlated with PFS and response rate following bevacizumab (all adjusted interaction P < 0.05). A baseline CAF signature combining these three markers has greater predictive ability than individual markers. Signature-negative patients showed impaired survival following bevacizumab treatment (PFS, 7.3 vs 7.0 months; hazard ratio [HR] 1.03; OS, 29.9 vs 21.1 months, HR 1.33) compared with signature-positive patients (PFS, 6.5 vs 11.9 months, HR 0.52; OS, 28.0 vs 55.3 months, HR 0.67). These promising results warrant further prospective studies.

No MeSH data available.


Related in: MedlinePlus