Phase II study of bevacizumab and preoperative chemoradiation for esophageal adenocarcinoma

Geoffrey Y. Ku, Manjit S. Bains, Do Joong Park, Yelena Y. Janjigian, Valerie W. Rusch, Nabil P. Rizk, Sam S. Yoon, Brittanie Millang, Marinela Capanu, Karyn A. Goodman, David H. Ilson

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Background: A standard-of-care for locally advanced esophageal and gastroesophageal junction (GEJ) adenocarcinoma is pre-operative chemoradiation. Elevated levels of vascular endothelial growth factor (VEGF) have been associated with worse outcomes following chemoradiation and anti-VEGF therapies can potentiate radiation efficacy. Methods: In this single-arm phase II study, we added bevacizumab to induction chemotherapy and concurrent chemoradiation with cisplatin/irinotecan for locally advanced esophageal and GEJ adenocarcinomas. Results: Thirty-three patients were enrolled, with all evaluable. All tumors involved the GEJ and 67% were node-positive by endoscopic ultrasound (EUS) and imaging. Twenty-eight patients completed chemoradiation and 26 patients underwent surgery (25 R0 resections). Toxicities were not clearly increased. The pathologic complete response (pCR) rate was 15%. Median progression-free survival (PFS) and overall survival (OS) were 15.1 and 30.5 months respectively. Higher baseline VEGF-A levels were associated with a trend toward improved OS (not reached vs. 21.0 months, P=0.11). Response on positron emission tomography (PET) scan after induction chemotherapy was predictive of PFS and showed trends toward improved OS and pCR rate. Conclusions: The addition of bevacizumab to chemoradiation was not associated with clear worsening of toxicities but also led to no improvement in outcomes, when compared to a prior phase II study of 55 patients. Higher baseline VEGF-A levels correlated with a trend toward improved survival and might be used to stratify or select patients for future studies incorporating this or similar agents. PET scan to assess response following induction chemotherapy and change chemotherapy in non-responders during chemoradiation is the subject of a fully-accrued national trial (NCT01333033).

Original languageEnglish
Pages (from-to)828-837
Number of pages10
JournalJournal of Gastrointestinal Oncology
Volume7
Issue number6
DOIs
StatePublished - 1 Jan 2016

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Adenocarcinoma
Esophagogastric Junction
Vascular Endothelial Growth Factor A
Induction Chemotherapy
irinotecan
Survival
Positron-Emission Tomography
Disease-Free Survival
Standard of Care
Cisplatin
Ultrasonography
Bevacizumab
Radiation
Drug Therapy
Neoplasms
Therapeutics

Keywords

  • Adenocarcinoma
  • Bevacizumab
  • Chemoradiation
  • Chemotherapy
  • Esophageal cancer
  • Radiation

Cite this

Ku, Geoffrey Y. ; Bains, Manjit S. ; Park, Do Joong ; Janjigian, Yelena Y. ; Rusch, Valerie W. ; Rizk, Nabil P. ; Yoon, Sam S. ; Millang, Brittanie ; Capanu, Marinela ; Goodman, Karyn A. ; Ilson, David H. / Phase II study of bevacizumab and preoperative chemoradiation for esophageal adenocarcinoma. In: Journal of Gastrointestinal Oncology. 2016 ; Vol. 7, No. 6. pp. 828-837.
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abstract = "Background: A standard-of-care for locally advanced esophageal and gastroesophageal junction (GEJ) adenocarcinoma is pre-operative chemoradiation. Elevated levels of vascular endothelial growth factor (VEGF) have been associated with worse outcomes following chemoradiation and anti-VEGF therapies can potentiate radiation efficacy. Methods: In this single-arm phase II study, we added bevacizumab to induction chemotherapy and concurrent chemoradiation with cisplatin/irinotecan for locally advanced esophageal and GEJ adenocarcinomas. Results: Thirty-three patients were enrolled, with all evaluable. All tumors involved the GEJ and 67{\%} were node-positive by endoscopic ultrasound (EUS) and imaging. Twenty-eight patients completed chemoradiation and 26 patients underwent surgery (25 R0 resections). Toxicities were not clearly increased. The pathologic complete response (pCR) rate was 15{\%}. Median progression-free survival (PFS) and overall survival (OS) were 15.1 and 30.5 months respectively. Higher baseline VEGF-A levels were associated with a trend toward improved OS (not reached vs. 21.0 months, P=0.11). Response on positron emission tomography (PET) scan after induction chemotherapy was predictive of PFS and showed trends toward improved OS and pCR rate. Conclusions: The addition of bevacizumab to chemoradiation was not associated with clear worsening of toxicities but also led to no improvement in outcomes, when compared to a prior phase II study of 55 patients. Higher baseline VEGF-A levels correlated with a trend toward improved survival and might be used to stratify or select patients for future studies incorporating this or similar agents. PET scan to assess response following induction chemotherapy and change chemotherapy in non-responders during chemoradiation is the subject of a fully-accrued national trial (NCT01333033).",
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author = "Ku, {Geoffrey Y.} and Bains, {Manjit S.} and Park, {Do Joong} and Janjigian, {Yelena Y.} and Rusch, {Valerie W.} and Rizk, {Nabil P.} and Yoon, {Sam S.} and Brittanie Millang and Marinela Capanu and Goodman, {Karyn A.} and Ilson, {David H.}",
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Ku, GY, Bains, MS, Park, DJ, Janjigian, YY, Rusch, VW, Rizk, NP, Yoon, SS, Millang, B, Capanu, M, Goodman, KA & Ilson, DH 2016, 'Phase II study of bevacizumab and preoperative chemoradiation for esophageal adenocarcinoma', Journal of Gastrointestinal Oncology, vol. 7, no. 6, pp. 828-837. https://doi.org/10.21037/jgo.2016.08.09

Phase II study of bevacizumab and preoperative chemoradiation for esophageal adenocarcinoma. / Ku, Geoffrey Y.; Bains, Manjit S.; Park, Do Joong; Janjigian, Yelena Y.; Rusch, Valerie W.; Rizk, Nabil P.; Yoon, Sam S.; Millang, Brittanie; Capanu, Marinela; Goodman, Karyn A.; Ilson, David H.

In: Journal of Gastrointestinal Oncology, Vol. 7, No. 6, 01.01.2016, p. 828-837.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Phase II study of bevacizumab and preoperative chemoradiation for esophageal adenocarcinoma

AU - Ku, Geoffrey Y.

AU - Bains, Manjit S.

AU - Park, Do Joong

AU - Janjigian, Yelena Y.

AU - Rusch, Valerie W.

AU - Rizk, Nabil P.

AU - Yoon, Sam S.

AU - Millang, Brittanie

AU - Capanu, Marinela

AU - Goodman, Karyn A.

AU - Ilson, David H.

PY - 2016/1/1

Y1 - 2016/1/1

N2 - Background: A standard-of-care for locally advanced esophageal and gastroesophageal junction (GEJ) adenocarcinoma is pre-operative chemoradiation. Elevated levels of vascular endothelial growth factor (VEGF) have been associated with worse outcomes following chemoradiation and anti-VEGF therapies can potentiate radiation efficacy. Methods: In this single-arm phase II study, we added bevacizumab to induction chemotherapy and concurrent chemoradiation with cisplatin/irinotecan for locally advanced esophageal and GEJ adenocarcinomas. Results: Thirty-three patients were enrolled, with all evaluable. All tumors involved the GEJ and 67% were node-positive by endoscopic ultrasound (EUS) and imaging. Twenty-eight patients completed chemoradiation and 26 patients underwent surgery (25 R0 resections). Toxicities were not clearly increased. The pathologic complete response (pCR) rate was 15%. Median progression-free survival (PFS) and overall survival (OS) were 15.1 and 30.5 months respectively. Higher baseline VEGF-A levels were associated with a trend toward improved OS (not reached vs. 21.0 months, P=0.11). Response on positron emission tomography (PET) scan after induction chemotherapy was predictive of PFS and showed trends toward improved OS and pCR rate. Conclusions: The addition of bevacizumab to chemoradiation was not associated with clear worsening of toxicities but also led to no improvement in outcomes, when compared to a prior phase II study of 55 patients. Higher baseline VEGF-A levels correlated with a trend toward improved survival and might be used to stratify or select patients for future studies incorporating this or similar agents. PET scan to assess response following induction chemotherapy and change chemotherapy in non-responders during chemoradiation is the subject of a fully-accrued national trial (NCT01333033).

AB - Background: A standard-of-care for locally advanced esophageal and gastroesophageal junction (GEJ) adenocarcinoma is pre-operative chemoradiation. Elevated levels of vascular endothelial growth factor (VEGF) have been associated with worse outcomes following chemoradiation and anti-VEGF therapies can potentiate radiation efficacy. Methods: In this single-arm phase II study, we added bevacizumab to induction chemotherapy and concurrent chemoradiation with cisplatin/irinotecan for locally advanced esophageal and GEJ adenocarcinomas. Results: Thirty-three patients were enrolled, with all evaluable. All tumors involved the GEJ and 67% were node-positive by endoscopic ultrasound (EUS) and imaging. Twenty-eight patients completed chemoradiation and 26 patients underwent surgery (25 R0 resections). Toxicities were not clearly increased. The pathologic complete response (pCR) rate was 15%. Median progression-free survival (PFS) and overall survival (OS) were 15.1 and 30.5 months respectively. Higher baseline VEGF-A levels were associated with a trend toward improved OS (not reached vs. 21.0 months, P=0.11). Response on positron emission tomography (PET) scan after induction chemotherapy was predictive of PFS and showed trends toward improved OS and pCR rate. Conclusions: The addition of bevacizumab to chemoradiation was not associated with clear worsening of toxicities but also led to no improvement in outcomes, when compared to a prior phase II study of 55 patients. Higher baseline VEGF-A levels correlated with a trend toward improved survival and might be used to stratify or select patients for future studies incorporating this or similar agents. PET scan to assess response following induction chemotherapy and change chemotherapy in non-responders during chemoradiation is the subject of a fully-accrued national trial (NCT01333033).

KW - Adenocarcinoma

KW - Bevacizumab

KW - Chemoradiation

KW - Chemotherapy

KW - Esophageal cancer

KW - Radiation

UR - http://www.scopus.com/inward/record.url?scp=85006966018&partnerID=8YFLogxK

U2 - 10.21037/jgo.2016.08.09

DO - 10.21037/jgo.2016.08.09

M3 - Article

AN - SCOPUS:85006966018

VL - 7

SP - 828

EP - 837

JO - Journal of Gastrointestinal Oncology

JF - Journal of Gastrointestinal Oncology

SN - 2078-6891

IS - 6

ER -