Published Ahead of Print on February 16, 2016 as 10.1200/JCO.2015.65.8666 The latest version is at http://jco.ascopubs.org/cgi/doi/10.1200/JCO.2015.65.8666
JOURNAL OF CLINICAL ONCOLOGY
E D I T O R I A L
Targeting the Vascular Endothelial Growth Factor Pathway in Gastric Cancer: A Hit or a Miss? David H. Ilson, Memorial Sloan-Kettering Cancer Center, New York, NY See accompanying article doi:10.1200/JCO.2015.63.5995
Gastric cancer is the third leading cause of cancer-related mortality globally, and China is the epicenter of gastric cancer incidence, accounting for nearly half of the world’s cases.1 In the article that accompanies this editorial, Chinese investigators led by Jin Li2 report positive results for the multitargeted tyrosine kinase inhibitor apatinib, which also targets the vascular endothelial growth factor receptor 2 (VEGFR2) kinase, in chemotherapy-refractory gastric cancer. Although no responses were seen, overall survival, the primary end point, was improved by a median of 1.8 months with apatinib treatment, which translated into a 30% short-term reduction in the risk of death. This study adds to incremental but modest gains in survival achieved in recent clinical trials in gastric cancer. How will VEGFtargeted therapies move forward in the treatment of gastric cancer, and how do we put these results into the context of other recent advances? In the arena of targeted therapies, the VEGF pathway has been an early and ongoing focus of drug development, given its pivotal role in tumor growth, invasion, and metastasis. Despite the failure to achieve a survival improvement for use of bevacizumab combined with first-line chemotherapy in gastric cancer,3 recent studies of VEGF-directed therapies have yielded positive results in later-line therapy. Ramucirumab, which blocks ligand binding to the VEGFR2 receptor, achieved modest survival benefits (1.4 months) as a single agent in a second-line trial in gastric cancer4 and when combined with second-line paclitaxel (2.2 months).5 The results now reported for apatinib are consistent with these earlier observations, and the similar but small survival improvements across these trials add to evidence that the VEGF pathway is a viable therapeutic target. Whether it is better to target the VEGFR2 tyrosine kinase or the receptor itself will require earlier-line study of both ramucirumab and apatinib. An ongoing phase III trial is evaluating ramucirumab in combination with first-line capecitabine plus cisplatin chemotherapy in metastatic esophagogastric cancer (ClinicalTrials.gov identifier NCI-2015-00221). In addition to combination with chemotherapy, VEGF-targeted agents will also move forward as part of targeted therapy combinations, given the potential for these agents to modify the tumor microenvironment and interact with immunomodulatory pathways and other receptor-associated tyrosine kinases through receptor cross talk. Whether VEGF-targeted agents may be useful as maintenance therapy, either sequenced with or combined with chemotherapy, will be an important study question as well. Negative results, however, were recently reported for VEGF-targeted therapy combined with adjuvant perioperative chemotherapy and gastric
cancer resection: the recent 1,000-patient British ST03 trial failed to demonstrate any survival benefit for the addition of bevacizumab to perioperative chemotherapy.6 Because there currently is no biomarker to identify patients who may experience greater benefit from VEGF-targeted agents, the negative results of this large trial have dampened interest in the study of VEGF-targeted agents as part of adjuvant therapy. The greatest incremental benefit for targeted therapy is seen when a biomarker is used to enrich the study population, as evidenced by the positive results achieved for trastuzumab in human epidermal growth factor receptor 2–positive gastric cancer7; those patients with the highest overexpression of human epidermal growth factor receptor 2 achieved the greatest treatment benefit. In patients without biomarker selection, recent large randomized trials of epidermal growth factor receptor–targeted antibodies failed to improve outcome in first-line chemotherapy, with a detriment actually seen for adding these agents to chemotherapy. 8,9 However, biomarkers that were predicted to select patients most likely to benefit from targeted strategies have also failed. The recent negative and sobering experience with MET pathway inhibitors both in immunohistochemically and gene amplification selected populations,10,11 even with strong signals for these agents in prior phase I/II trials, indicates the need ultimately for larger-scale validation of both biomarkers and novel therapies. Results from The Cancer Genome Atlas studies in esophagogastric cancer may provide a roadmap for stratification of patients in future trial design, as could retrospective evaluation of completed clinical trials to assess the impact of gastric cancer molecular classification.12 The identification of molecular subsets with higher rates of genomic amplification of targetable receptorassociated tyrosine kinase pathways, along with higher rates of PIK3CA kinase mutation, microsatellite instability, and overexpression of the ligands programmed death-ligands 1 and 2, may lead to enrichment of populations more likely to benefit from specific targeted therapies and immunotherapies. The modest survival improvement achieved with agents like apatinib and ramucirumab requires study of the relative cost versus the benefit. A recent cost analysis of the drug regorafenib in refractory colorectal cancer13 indicated that the benefit of a new therapy might come at a potentially unacceptable cost. Also, in later-line therapy trials, given the poor short-term survival, although small incremental improvements with new therapies
© 2016 by American Society of Clinical Oncology
Downloaded from jco.ascopubs.org on March 10, 2016. For personal use only. No other uses without permission. Copyright © 2016 American Society of Clinical Oncology. All rights reserved.
Copyright 2016 by American Society of Clinical Oncology
1
Editorial
translate into impressive hazard ratios that achieve statistical significance, are they clinically meaningful? The direction of future trials in esophagogastric cancer, in both advanced disease and in the adjuvant setting, will be shaped by several recent results. In metastatic disease, two-drug regimens have received increasing support as the preferred first-line chemotherapy; the recent French Intergroup Trial, published last year in JCO, questioned whether anthracycline triplet therapy was any better than the two-drug regimen FOLFIRI (fluorouracil, leucovorin, and irinotecan).14 ECX (epirubicin, cisplatin, and capecitabine) and EOX (epirubicin, oxaliplatin, and capecitabine), the stalwarts of gastric cancer chemotherapy in the United Kingdom, also recently proved poor partners when combined with agents targeting the epidermal growth factor receptor8 or MET10 pathways. Recent trials in esophagogastric cancer have also failed to demonstrate a survival benefit for the addition of epirubicin to fluorinated pyrimidine–based adjuvant chemotherapy15,16 and whether any survival benefit is achieved by extending the duration of chemotherapy treatment beyond 6 to 12 weeks.16,17 Using less toxic regimens, potentially for a shorter duration, will enhance the opportunity to combine novel agents with systemic chemotherapy and will potentially allow the introduction of novel therapeutic strategies earlier on in the adjuvant setting. AUTHOR’S DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST
Disclosures provided by the authors are available with this article at www.jco.org. REFERENCES 1. Jemal A, Bray F, Center MM, et al: Global cancer statistics. CA Cancer J Clin 61:69-90, 2011 2. Li J, Qin S, Xu J, et al: Randomized, double-blind, placebo-controlled phase III trial of apatinib in patients with chemotherapy-refractory advanced or metastatic adenocarcinoma of the stomach or gastroesophageal junction. J Clin Oncol doi: 10.1200/JCO.2015.63.5995 3. Ohtsu A, Shah MA, Van Cutsem E, et al: Bevacizumab in combination with chemotherapy as first-line therapy in advanced gastric cancer: A randomized, double-blind, placebo-controlled phase III study. J Clin Oncol 29:3968-3976, 2011 4. Fuchs CS, Tomasek J, Yong CJ, et al; REGARD trial investigators: Ramucirumab monotherapy for previously treated advanced gastric or gastrooesophageal junction adenocarcinoma (REGARD): An international, randomised, multicentre, placebo-controlled, phase 3 trial. Lancet 383:31-39, 2014 5. Wilke H, Muro K, Van Cutsem E, et al; RAINBOW Study Group: Ramucirumab plus paclitaxel versus placebo plus paclitaxel in patients with previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma (RAINBOW): A double-blind, randomised phase 3 trial. Lancet Oncol 15:1224-1235, 2014 6. Cunningham D, Smyth E, Stenning S, et al: Perioperative chemotherapy 1 / - bevacizumab for resectable gastroesophageal adenocarcinoma: Results
from the UK Medical Research Council randomized ST03 trial (ISRCTN 46020948). Presented at the European Cancer Congress, Vienna, Austria, September 25-29, 2015 7. Bang YJ, Van Cutsem E, Feyereislova A, et al; ToGA trial investigators: Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): A phase 3, open-label, randomised controlled trial. Lancet 376: 687-697, 2010 8. Waddell T, Chau I, Cunningham D, et al: Epirubicin, oxaliplatin, and capecitabine with or without panitumumab for patients with previously untreated advanced oesophagogastric cancer (REAL3): A randomised, openlabel phase 3 trial. Lancet Oncol 14:481-489, 2013 [erratum: Lancet Oncol 14: e254, 2013] 9. Bang YJ, Van Cutsem E, Feyereislova A, et al: Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-esophageal junction cancer (ToGA): A phase 3, openlabel, randomized controlled trial. Lancet Oncol 376:687-697, 2010 [erratum: Lancet 376:1302, 2010] 10. Cunningham D, Tebbutt NC, Davidenko I, et al: Phase III, randomized, double-blind, multicenter, placebo (P)-controlled trial of rilotumumab (R) plus epirubicin, cisplatin and capecitabine (ECX) as first-line therapy in patients (pts) with advanced MET-positive (pos) gastric or gastroesophageal junction (G/GEJ) cancer: RILOMET-1 study. J Clin Oncol 33, 2015 (suppl; abstr 4000) 11. Shah MA, Bang Y-J, Lordick F, et al: METGastric: A phase III study of onartuzumab plus mFOLFOX6 in patients with metastatic HER2-negative (HER2-) and MET-positive (MET1) adenocarcinoma of the stomach or gastroesophageal junction (GEC). J Clin Oncol 33, 2015 (suppl; abstr 4012) 12. Cancer Genome Atlas Research Network: Comprehensive molecular characterization of gastric adenocarcinoma. Nature 513:202-209, 2014 13. Goldstein DA, Ahmad BB, Chen Q, et al: Cost-effectiveness analysis of regorafenib for metastatic colorectal cancer. J Clin Oncol 33:3727-3732, 2015 14. Guimbaud R, Louvet C, Ries P, et al: Prospective, randomized, multicenter, phase III study of fluorouracil, leucovorin, and irinotecan versus epirubicin, cisplatin, and capecitabine in advanced gastric adenocarcinoma: A French intergroup ´ eration ´ ´ ´ eration ´ (Fed Francophone de Cancerologie Digestive, Fed Nationale des ´ Centres de Lutte Contre le Cancer, and Groupe Cooperateur Multidisciplinaire en Oncologie) study. J Clin Oncol 32:3520-3526, 2014 15. Fuchs CS, Tepper JE, Niedziewcki D, et al: Postoperative adjuvant chemoradiation for gastric or gastroesophageal junction (GEJ) adenocarcinoma using epirubicin, cisplatin, and infusional (CI) 5-FU (ECF) before and after CI 5-FU and radiotherapy (CRT) compared with bolus 5-FU/LV before and after CRT: Intergroup trial CALGB 80101. J Clin Oncol 29, 2011 (suppl; abstr 4003) 16. Alderson D, Langley RE, Nankivell NG, et al: Neoadjuvant chemotherapy for resectable esophageal and junctional adenocarcinoma: Results from the UK Medical Research Council randomized OEO5 trial (ISRCTN 01852072). J Clin Oncol 33, 2015 (suppl; abstr 4002) 17. Kang YK, Chang HM, Yook JH, et al: Adjuvant chemotherapy for gastric cancer: A randomised phase 3 trial of mitomycin-C plus either short-term doxifluridine or long-term doxifluridine plus cisplatin after curative D2 gastrectomy (AMC0201). Br J Cancer 108:1245-1251, 2013
DOI: 10.1200/JCO.2015.65.8666; published online ahead of print at www.jco.org on February 16, 2016.
n n n
2
© 2016 by American Society of Clinical Oncology
JOURNAL OF CLINICAL ONCOLOGY
Downloaded from jco.ascopubs.org on March 10, 2016. For personal use only. No other uses without permission. Copyright © 2016 American Society of Clinical Oncology. All rights reserved.
Editorial
AUTHOR’S DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST
Targeting the Vascular Endothelial Growth Factor Pathway in Gastric Cancer: A Hit or a Miss? The following represents disclosure information provided by authors of this manuscript. All relationships are considered compensated. Relationships are self-held unless noted. I 5 Immediate Family Member, Inst 5 My Institution. Relationships may not relate to the subject matter of this manuscript. For more information about ASCO’s conflict of interest policy, please refer to www.asco.org/rwc or jco.ascopubs.org/site/ifc. David H. Ilson Consulting or Advisory Role: Amgen, Eli Lilly/ImClone, Roche/ Genentech Speakers’ Bureau: Eli Lilly/ImClone Research Funding: Bayer, Amgen, Bristol-Myers Squibb Travel, Accommodations, Expenses: Eli Lilly/ImClone, Amgen
www.jco.org
© 2016 by American Society of Clinical Oncology
Downloaded from jco.ascopubs.org on March 10, 2016. For personal use only. No other uses without permission. Copyright © 2016 American Society of Clinical Oncology. All rights reserved.
JOURNAL OF CLINICAL ONCOLOGY
E D I T O R I A L
Targeting the Vascular Endothelial Growth Factor Pathway in Gastric Cancer: A Hit or a Miss? David H. Ilson, Memorial Sloan-Kettering Cancer Center, New York, NY See accompanying article doi:10.1200/JCO.2015.63.5995
Gastric cancer is the third leading cause of cancer-related mortality globally, and China is the epicenter of gastric cancer incidence, accounting for nearly half of the world’s cases.1 In the article that accompanies this editorial, Chinese investigators led by Jin Li2 report positive results for the multitargeted tyrosine kinase inhibitor apatinib, which also targets the vascular endothelial growth factor receptor 2 (VEGFR2) kinase, in chemotherapy-refractory gastric cancer. Although no responses were seen, overall survival, the primary end point, was improved by a median of 1.8 months with apatinib treatment, which translated into a 30% short-term reduction in the risk of death. This study adds to incremental but modest gains in survival achieved in recent clinical trials in gastric cancer. How will VEGFtargeted therapies move forward in the treatment of gastric cancer, and how do we put these results into the context of other recent advances? In the arena of targeted therapies, the VEGF pathway has been an early and ongoing focus of drug development, given its pivotal role in tumor growth, invasion, and metastasis. Despite the failure to achieve a survival improvement for use of bevacizumab combined with first-line chemotherapy in gastric cancer,3 recent studies of VEGF-directed therapies have yielded positive results in later-line therapy. Ramucirumab, which blocks ligand binding to the VEGFR2 receptor, achieved modest survival benefits (1.4 months) as a single agent in a second-line trial in gastric cancer4 and when combined with second-line paclitaxel (2.2 months).5 The results now reported for apatinib are consistent with these earlier observations, and the similar but small survival improvements across these trials add to evidence that the VEGF pathway is a viable therapeutic target. Whether it is better to target the VEGFR2 tyrosine kinase or the receptor itself will require earlier-line study of both ramucirumab and apatinib. An ongoing phase III trial is evaluating ramucirumab in combination with first-line capecitabine plus cisplatin chemotherapy in metastatic esophagogastric cancer (ClinicalTrials.gov identifier NCI-2015-00221). In addition to combination with chemotherapy, VEGF-targeted agents will also move forward as part of targeted therapy combinations, given the potential for these agents to modify the tumor microenvironment and interact with immunomodulatory pathways and other receptor-associated tyrosine kinases through receptor cross talk. Whether VEGF-targeted agents may be useful as maintenance therapy, either sequenced with or combined with chemotherapy, will be an important study question as well. Negative results, however, were recently reported for VEGF-targeted therapy combined with adjuvant perioperative chemotherapy and gastric
cancer resection: the recent 1,000-patient British ST03 trial failed to demonstrate any survival benefit for the addition of bevacizumab to perioperative chemotherapy.6 Because there currently is no biomarker to identify patients who may experience greater benefit from VEGF-targeted agents, the negative results of this large trial have dampened interest in the study of VEGF-targeted agents as part of adjuvant therapy. The greatest incremental benefit for targeted therapy is seen when a biomarker is used to enrich the study population, as evidenced by the positive results achieved for trastuzumab in human epidermal growth factor receptor 2–positive gastric cancer7; those patients with the highest overexpression of human epidermal growth factor receptor 2 achieved the greatest treatment benefit. In patients without biomarker selection, recent large randomized trials of epidermal growth factor receptor–targeted antibodies failed to improve outcome in first-line chemotherapy, with a detriment actually seen for adding these agents to chemotherapy. 8,9 However, biomarkers that were predicted to select patients most likely to benefit from targeted strategies have also failed. The recent negative and sobering experience with MET pathway inhibitors both in immunohistochemically and gene amplification selected populations,10,11 even with strong signals for these agents in prior phase I/II trials, indicates the need ultimately for larger-scale validation of both biomarkers and novel therapies. Results from The Cancer Genome Atlas studies in esophagogastric cancer may provide a roadmap for stratification of patients in future trial design, as could retrospective evaluation of completed clinical trials to assess the impact of gastric cancer molecular classification.12 The identification of molecular subsets with higher rates of genomic amplification of targetable receptorassociated tyrosine kinase pathways, along with higher rates of PIK3CA kinase mutation, microsatellite instability, and overexpression of the ligands programmed death-ligands 1 and 2, may lead to enrichment of populations more likely to benefit from specific targeted therapies and immunotherapies. The modest survival improvement achieved with agents like apatinib and ramucirumab requires study of the relative cost versus the benefit. A recent cost analysis of the drug regorafenib in refractory colorectal cancer13 indicated that the benefit of a new therapy might come at a potentially unacceptable cost. Also, in later-line therapy trials, given the poor short-term survival, although small incremental improvements with new therapies
© 2016 by American Society of Clinical Oncology
Downloaded from jco.ascopubs.org on March 10, 2016. For personal use only. No other uses without permission. Copyright © 2016 American Society of Clinical Oncology. All rights reserved.
Copyright 2016 by American Society of Clinical Oncology
1
Editorial
translate into impressive hazard ratios that achieve statistical significance, are they clinically meaningful? The direction of future trials in esophagogastric cancer, in both advanced disease and in the adjuvant setting, will be shaped by several recent results. In metastatic disease, two-drug regimens have received increasing support as the preferred first-line chemotherapy; the recent French Intergroup Trial, published last year in JCO, questioned whether anthracycline triplet therapy was any better than the two-drug regimen FOLFIRI (fluorouracil, leucovorin, and irinotecan).14 ECX (epirubicin, cisplatin, and capecitabine) and EOX (epirubicin, oxaliplatin, and capecitabine), the stalwarts of gastric cancer chemotherapy in the United Kingdom, also recently proved poor partners when combined with agents targeting the epidermal growth factor receptor8 or MET10 pathways. Recent trials in esophagogastric cancer have also failed to demonstrate a survival benefit for the addition of epirubicin to fluorinated pyrimidine–based adjuvant chemotherapy15,16 and whether any survival benefit is achieved by extending the duration of chemotherapy treatment beyond 6 to 12 weeks.16,17 Using less toxic regimens, potentially for a shorter duration, will enhance the opportunity to combine novel agents with systemic chemotherapy and will potentially allow the introduction of novel therapeutic strategies earlier on in the adjuvant setting. AUTHOR’S DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST
Disclosures provided by the authors are available with this article at www.jco.org. REFERENCES 1. Jemal A, Bray F, Center MM, et al: Global cancer statistics. CA Cancer J Clin 61:69-90, 2011 2. Li J, Qin S, Xu J, et al: Randomized, double-blind, placebo-controlled phase III trial of apatinib in patients with chemotherapy-refractory advanced or metastatic adenocarcinoma of the stomach or gastroesophageal junction. J Clin Oncol doi: 10.1200/JCO.2015.63.5995 3. Ohtsu A, Shah MA, Van Cutsem E, et al: Bevacizumab in combination with chemotherapy as first-line therapy in advanced gastric cancer: A randomized, double-blind, placebo-controlled phase III study. J Clin Oncol 29:3968-3976, 2011 4. Fuchs CS, Tomasek J, Yong CJ, et al; REGARD trial investigators: Ramucirumab monotherapy for previously treated advanced gastric or gastrooesophageal junction adenocarcinoma (REGARD): An international, randomised, multicentre, placebo-controlled, phase 3 trial. Lancet 383:31-39, 2014 5. Wilke H, Muro K, Van Cutsem E, et al; RAINBOW Study Group: Ramucirumab plus paclitaxel versus placebo plus paclitaxel in patients with previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma (RAINBOW): A double-blind, randomised phase 3 trial. Lancet Oncol 15:1224-1235, 2014 6. Cunningham D, Smyth E, Stenning S, et al: Perioperative chemotherapy 1 / - bevacizumab for resectable gastroesophageal adenocarcinoma: Results
from the UK Medical Research Council randomized ST03 trial (ISRCTN 46020948). Presented at the European Cancer Congress, Vienna, Austria, September 25-29, 2015 7. Bang YJ, Van Cutsem E, Feyereislova A, et al; ToGA trial investigators: Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): A phase 3, open-label, randomised controlled trial. Lancet 376: 687-697, 2010 8. Waddell T, Chau I, Cunningham D, et al: Epirubicin, oxaliplatin, and capecitabine with or without panitumumab for patients with previously untreated advanced oesophagogastric cancer (REAL3): A randomised, openlabel phase 3 trial. Lancet Oncol 14:481-489, 2013 [erratum: Lancet Oncol 14: e254, 2013] 9. Bang YJ, Van Cutsem E, Feyereislova A, et al: Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-esophageal junction cancer (ToGA): A phase 3, openlabel, randomized controlled trial. Lancet Oncol 376:687-697, 2010 [erratum: Lancet 376:1302, 2010] 10. Cunningham D, Tebbutt NC, Davidenko I, et al: Phase III, randomized, double-blind, multicenter, placebo (P)-controlled trial of rilotumumab (R) plus epirubicin, cisplatin and capecitabine (ECX) as first-line therapy in patients (pts) with advanced MET-positive (pos) gastric or gastroesophageal junction (G/GEJ) cancer: RILOMET-1 study. J Clin Oncol 33, 2015 (suppl; abstr 4000) 11. Shah MA, Bang Y-J, Lordick F, et al: METGastric: A phase III study of onartuzumab plus mFOLFOX6 in patients with metastatic HER2-negative (HER2-) and MET-positive (MET1) adenocarcinoma of the stomach or gastroesophageal junction (GEC). J Clin Oncol 33, 2015 (suppl; abstr 4012) 12. Cancer Genome Atlas Research Network: Comprehensive molecular characterization of gastric adenocarcinoma. Nature 513:202-209, 2014 13. Goldstein DA, Ahmad BB, Chen Q, et al: Cost-effectiveness analysis of regorafenib for metastatic colorectal cancer. J Clin Oncol 33:3727-3732, 2015 14. Guimbaud R, Louvet C, Ries P, et al: Prospective, randomized, multicenter, phase III study of fluorouracil, leucovorin, and irinotecan versus epirubicin, cisplatin, and capecitabine in advanced gastric adenocarcinoma: A French intergroup ´ eration ´ ´ ´ eration ´ (Fed Francophone de Cancerologie Digestive, Fed Nationale des ´ Centres de Lutte Contre le Cancer, and Groupe Cooperateur Multidisciplinaire en Oncologie) study. J Clin Oncol 32:3520-3526, 2014 15. Fuchs CS, Tepper JE, Niedziewcki D, et al: Postoperative adjuvant chemoradiation for gastric or gastroesophageal junction (GEJ) adenocarcinoma using epirubicin, cisplatin, and infusional (CI) 5-FU (ECF) before and after CI 5-FU and radiotherapy (CRT) compared with bolus 5-FU/LV before and after CRT: Intergroup trial CALGB 80101. J Clin Oncol 29, 2011 (suppl; abstr 4003) 16. Alderson D, Langley RE, Nankivell NG, et al: Neoadjuvant chemotherapy for resectable esophageal and junctional adenocarcinoma: Results from the UK Medical Research Council randomized OEO5 trial (ISRCTN 01852072). J Clin Oncol 33, 2015 (suppl; abstr 4002) 17. Kang YK, Chang HM, Yook JH, et al: Adjuvant chemotherapy for gastric cancer: A randomised phase 3 trial of mitomycin-C plus either short-term doxifluridine or long-term doxifluridine plus cisplatin after curative D2 gastrectomy (AMC0201). Br J Cancer 108:1245-1251, 2013
DOI: 10.1200/JCO.2015.65.8666; published online ahead of print at www.jco.org on February 16, 2016.
n n n
2
© 2016 by American Society of Clinical Oncology
JOURNAL OF CLINICAL ONCOLOGY
Downloaded from jco.ascopubs.org on March 10, 2016. For personal use only. No other uses without permission. Copyright © 2016 American Society of Clinical Oncology. All rights reserved.
Editorial
AUTHOR’S DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST
Targeting the Vascular Endothelial Growth Factor Pathway in Gastric Cancer: A Hit or a Miss? The following represents disclosure information provided by authors of this manuscript. All relationships are considered compensated. Relationships are self-held unless noted. I 5 Immediate Family Member, Inst 5 My Institution. Relationships may not relate to the subject matter of this manuscript. For more information about ASCO’s conflict of interest policy, please refer to www.asco.org/rwc or jco.ascopubs.org/site/ifc. David H. Ilson Consulting or Advisory Role: Amgen, Eli Lilly/ImClone, Roche/ Genentech Speakers’ Bureau: Eli Lilly/ImClone Research Funding: Bayer, Amgen, Bristol-Myers Squibb Travel, Accommodations, Expenses: Eli Lilly/ImClone, Amgen
www.jco.org
© 2016 by American Society of Clinical Oncology
Downloaded from jco.ascopubs.org on March 10, 2016. For personal use only. No other uses without permission. Copyright © 2016 American Society of Clinical Oncology. All rights reserved.
