A randomized phase II study of FOLFOX with or without the MET inhibitor onartuzumab in advanced Adenocarcinoma of the stomach and Gastroesophageal junction

Manish A. Shah, Jae Yong Cho, Iain B. Tan, Niall C. Tebbutt, Chia-Jui Yen, Alice Kang, David S. Shames, Lilian Bu, Yoon Koo Kang

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Abstract

Background. The phase II YO28252 study (NCT01590719) examined first-line onartuzumab plus mFOLFOX6 in patients with metastatic, human epidermal growth factor receptor 2-negative adenocarcinoma of the stomach or gastroesophageal junction. MET immunohistochemistry expression as a biomarker of onartuzumab activity was also examined. Patients and Methods. Patients were randomized 1:1 to receive standard mFOLFOX6 plus onartuzumab (10 mg/kg) or placebo in 2-week cycles for 12 cycles,followed by onartuzumab or placebo until disease progression. Coprimary endpoints were progression-free survival (PFS) in intent-to-treat (ITT) and MET-positive populations. The target hazard ratio (HR) was 0.70 for patients in the ITT group and0.60 in the MET-positive population. Secondary end points were overall survival (OS), overall response rate (ORR), and safety. Results. Overall, 123patients were enrolled (n562onartuzumab, n 5 61 placebo). Median PFS was 6.77 versus 6.97 months for onartuzumab versus placebo, respectively (HR, 1.08; 95% confidence interval [CI], 0.71–1.63; p 5 = 71). In the MET-positive population, median PFS was 5.95 versus 6.80months, onartuzumab versus placebo (HR, 1.38; 95% CI, 0.60–3.20; p5.45).Median OS was 10.61 months for onartuzumab versus 11.27 months for placebo) (HR, 1.06, 0.64–1.75; p 5 =.83). In the MET-positive population, median OS was 8.51 versus 8.48 months for onartuzumab versus placebo, respectively (HR, 1.12, 95% CI, 0.45–2.78; p 5=.80). ORR was 60.5% for the onartuzumab group and 57.1%for placebo. Grade3–5adver see vents (AEs) wereseenin 88.3% of patients receiving onartuzumab and in 78.3% of patients receiving placebo, with serious AEs in 55% and 40%, respectively. Conclusion. Theaddition of onartuzumab to mFOLFOX6 ingastric cancer did not improve efficacy in an unselected population orin a MET immunohistochemistry-positive population.

Original languageEnglish
Pages (from-to)1085-1090
Number of pages6
JournalOncologist
Volume21
Issue number9
DOIs
Publication statusPublished - 2016 Sep 1

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Esophagogastric Junction
Stomach
Adenocarcinoma
Placebos
Population
Disease-Free Survival
Confidence Intervals
Survival
onartuzumab
Immunohistochemistry
Disease Progression
Biomarkers

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Shah, Manish A. ; Cho, Jae Yong ; Tan, Iain B. ; Tebbutt, Niall C. ; Yen, Chia-Jui ; Kang, Alice ; Shames, David S. ; Bu, Lilian ; Kang, Yoon Koo. / A randomized phase II study of FOLFOX with or without the MET inhibitor onartuzumab in advanced Adenocarcinoma of the stomach and Gastroesophageal junction. In: Oncologist. 2016 ; Vol. 21, No. 9. pp. 1085-1090.
@article{86c45c011c8d4e5b9f973400f7d85c80,
title = "A randomized phase II study of FOLFOX with or without the MET inhibitor onartuzumab in advanced Adenocarcinoma of the stomach and Gastroesophageal junction",
abstract = "Background. The phase II YO28252 study (NCT01590719) examined first-line onartuzumab plus mFOLFOX6 in patients with metastatic, human epidermal growth factor receptor 2-negative adenocarcinoma of the stomach or gastroesophageal junction. MET immunohistochemistry expression as a biomarker of onartuzumab activity was also examined. Patients and Methods. Patients were randomized 1:1 to receive standard mFOLFOX6 plus onartuzumab (10 mg/kg) or placebo in 2-week cycles for 12 cycles,followed by onartuzumab or placebo until disease progression. Coprimary endpoints were progression-free survival (PFS) in intent-to-treat (ITT) and MET-positive populations. The target hazard ratio (HR) was 0.70 for patients in the ITT group and0.60 in the MET-positive population. Secondary end points were overall survival (OS), overall response rate (ORR), and safety. Results. Overall, 123patients were enrolled (n562onartuzumab, n 5 61 placebo). Median PFS was 6.77 versus 6.97 months for onartuzumab versus placebo, respectively (HR, 1.08; 95{\%} confidence interval [CI], 0.71–1.63; p 5 = 71). In the MET-positive population, median PFS was 5.95 versus 6.80months, onartuzumab versus placebo (HR, 1.38; 95{\%} CI, 0.60–3.20; p5.45).Median OS was 10.61 months for onartuzumab versus 11.27 months for placebo) (HR, 1.06, 0.64–1.75; p 5 =.83). In the MET-positive population, median OS was 8.51 versus 8.48 months for onartuzumab versus placebo, respectively (HR, 1.12, 95{\%} CI, 0.45–2.78; p 5=.80). ORR was 60.5{\%} for the onartuzumab group and 57.1{\%}for placebo. Grade3–5adver see vents (AEs) wereseenin 88.3{\%} of patients receiving onartuzumab and in 78.3{\%} of patients receiving placebo, with serious AEs in 55{\%} and 40{\%}, respectively. Conclusion. Theaddition of onartuzumab to mFOLFOX6 ingastric cancer did not improve efficacy in an unselected population orin a MET immunohistochemistry-positive population.",
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A randomized phase II study of FOLFOX with or without the MET inhibitor onartuzumab in advanced Adenocarcinoma of the stomach and Gastroesophageal junction. / Shah, Manish A.; Cho, Jae Yong; Tan, Iain B.; Tebbutt, Niall C.; Yen, Chia-Jui; Kang, Alice; Shames, David S.; Bu, Lilian; Kang, Yoon Koo.

In: Oncologist, Vol. 21, No. 9, 01.09.2016, p. 1085-1090.

Research output: Contribution to journalArticle

TY - JOUR

T1 - A randomized phase II study of FOLFOX with or without the MET inhibitor onartuzumab in advanced Adenocarcinoma of the stomach and Gastroesophageal junction

AU - Shah, Manish A.

AU - Cho, Jae Yong

AU - Tan, Iain B.

AU - Tebbutt, Niall C.

AU - Yen, Chia-Jui

AU - Kang, Alice

AU - Shames, David S.

AU - Bu, Lilian

AU - Kang, Yoon Koo

PY - 2016/9/1

Y1 - 2016/9/1

N2 - Background. The phase II YO28252 study (NCT01590719) examined first-line onartuzumab plus mFOLFOX6 in patients with metastatic, human epidermal growth factor receptor 2-negative adenocarcinoma of the stomach or gastroesophageal junction. MET immunohistochemistry expression as a biomarker of onartuzumab activity was also examined. Patients and Methods. Patients were randomized 1:1 to receive standard mFOLFOX6 plus onartuzumab (10 mg/kg) or placebo in 2-week cycles for 12 cycles,followed by onartuzumab or placebo until disease progression. Coprimary endpoints were progression-free survival (PFS) in intent-to-treat (ITT) and MET-positive populations. The target hazard ratio (HR) was 0.70 for patients in the ITT group and0.60 in the MET-positive population. Secondary end points were overall survival (OS), overall response rate (ORR), and safety. Results. Overall, 123patients were enrolled (n562onartuzumab, n 5 61 placebo). Median PFS was 6.77 versus 6.97 months for onartuzumab versus placebo, respectively (HR, 1.08; 95% confidence interval [CI], 0.71–1.63; p 5 = 71). In the MET-positive population, median PFS was 5.95 versus 6.80months, onartuzumab versus placebo (HR, 1.38; 95% CI, 0.60–3.20; p5.45).Median OS was 10.61 months for onartuzumab versus 11.27 months for placebo) (HR, 1.06, 0.64–1.75; p 5 =.83). In the MET-positive population, median OS was 8.51 versus 8.48 months for onartuzumab versus placebo, respectively (HR, 1.12, 95% CI, 0.45–2.78; p 5=.80). ORR was 60.5% for the onartuzumab group and 57.1%for placebo. Grade3–5adver see vents (AEs) wereseenin 88.3% of patients receiving onartuzumab and in 78.3% of patients receiving placebo, with serious AEs in 55% and 40%, respectively. Conclusion. Theaddition of onartuzumab to mFOLFOX6 ingastric cancer did not improve efficacy in an unselected population orin a MET immunohistochemistry-positive population.

AB - Background. The phase II YO28252 study (NCT01590719) examined first-line onartuzumab plus mFOLFOX6 in patients with metastatic, human epidermal growth factor receptor 2-negative adenocarcinoma of the stomach or gastroesophageal junction. MET immunohistochemistry expression as a biomarker of onartuzumab activity was also examined. Patients and Methods. Patients were randomized 1:1 to receive standard mFOLFOX6 plus onartuzumab (10 mg/kg) or placebo in 2-week cycles for 12 cycles,followed by onartuzumab or placebo until disease progression. Coprimary endpoints were progression-free survival (PFS) in intent-to-treat (ITT) and MET-positive populations. The target hazard ratio (HR) was 0.70 for patients in the ITT group and0.60 in the MET-positive population. Secondary end points were overall survival (OS), overall response rate (ORR), and safety. Results. Overall, 123patients were enrolled (n562onartuzumab, n 5 61 placebo). Median PFS was 6.77 versus 6.97 months for onartuzumab versus placebo, respectively (HR, 1.08; 95% confidence interval [CI], 0.71–1.63; p 5 = 71). In the MET-positive population, median PFS was 5.95 versus 6.80months, onartuzumab versus placebo (HR, 1.38; 95% CI, 0.60–3.20; p5.45).Median OS was 10.61 months for onartuzumab versus 11.27 months for placebo) (HR, 1.06, 0.64–1.75; p 5 =.83). In the MET-positive population, median OS was 8.51 versus 8.48 months for onartuzumab versus placebo, respectively (HR, 1.12, 95% CI, 0.45–2.78; p 5=.80). ORR was 60.5% for the onartuzumab group and 57.1%for placebo. Grade3–5adver see vents (AEs) wereseenin 88.3% of patients receiving onartuzumab and in 78.3% of patients receiving placebo, with serious AEs in 55% and 40%, respectively. Conclusion. Theaddition of onartuzumab to mFOLFOX6 ingastric cancer did not improve efficacy in an unselected population orin a MET immunohistochemistry-positive population.

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