A phase II, randomized, double-blind, placebo-controlled study of simtuzumab in combination with FOLFIRI for the Second-Line treatment of metastatic KRAS mutant colorectal adenocarcinoma

J. Randolph Hecht, Al B. Benson, Dmitry Vyushkov, Yingsi Yang, Johanna Bendell, Udit Verma

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Background. Simtuzumab, a humanized IgG4 monoclonal antibody to lysyl oxidase-like 2 (LOXL2), blocks desmoplastic reaction in colorectal carcinoma (CRC) cells in vitro. Methods. Patients with metastatic Kirsten rat sarcoma viral oncogene homolog (KRAS) mutant CRC were randomized to receive second-line 5-fluorouracil, leucovorin, and irinotecan (FOLFIRI) with either 200 or 700 mg simtuzumab or placebo every 2 weeks in cycles of 28 days. Progression-free survival (PFS), overall survival (OS), objective response rate (ORR), and safety were assessed. Results. In total, 249 patients were randomized and treated with FOLFIRI/simtuzumab 700 mg (n584), FOLFIRI/simtuzumab 200 mg (n585), and FOLFIRI/placebo (n580). After a median follow-up of 5.1, 3.8, and 5.5 months, respectively, median PFS for each of the respective treatment groups was 5.5 months (adjusted HR [95% CI], p value versus placebo; 1.32 [0.92, 1.89]; p5.10), 5.4 months (1.45 [1.01, 2.06]; p5.04), and 5.8 months.Median OS was 11.4 months (1.23 [0.80, 1.91]; p5.25), 10.5 months (1.50 [0.98, 2.30]; p5.06), and 16.3 months, respectively. ORR was 11.9%, 5.9%, and 10%, respectively. Simtuzumab was tolerable in metastatic KRAS mutant CRC patients. Conclusion. The addition of simtuzumab to FOLFIRI did not improve clinical outcomes in patients with metastatic KRAS mutant CRC.

Original languageEnglish (US)
JournalOncologist
Volume22
Issue number3
DOIs
StatePublished - Mar 1 2017

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Colorectal Neoplasms
Adenocarcinoma
Placebos
irinotecan
Disease-Free Survival
Protein-Lysine 6-Oxidase
Antibodies, Monoclonal, Humanized
Survival
Leucovorin
Therapeutics
Oncogenes
Fluorouracil
Sarcoma
Immunoglobulin G
Safety

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

@article{f14996d475214a00982f2f06fbf2585d,
title = "A phase II, randomized, double-blind, placebo-controlled study of simtuzumab in combination with FOLFIRI for the Second-Line treatment of metastatic KRAS mutant colorectal adenocarcinoma",
abstract = "Background. Simtuzumab, a humanized IgG4 monoclonal antibody to lysyl oxidase-like 2 (LOXL2), blocks desmoplastic reaction in colorectal carcinoma (CRC) cells in vitro. Methods. Patients with metastatic Kirsten rat sarcoma viral oncogene homolog (KRAS) mutant CRC were randomized to receive second-line 5-fluorouracil, leucovorin, and irinotecan (FOLFIRI) with either 200 or 700 mg simtuzumab or placebo every 2 weeks in cycles of 28 days. Progression-free survival (PFS), overall survival (OS), objective response rate (ORR), and safety were assessed. Results. In total, 249 patients were randomized and treated with FOLFIRI/simtuzumab 700 mg (n584), FOLFIRI/simtuzumab 200 mg (n585), and FOLFIRI/placebo (n580). After a median follow-up of 5.1, 3.8, and 5.5 months, respectively, median PFS for each of the respective treatment groups was 5.5 months (adjusted HR [95{\%} CI], p value versus placebo; 1.32 [0.92, 1.89]; p5.10), 5.4 months (1.45 [1.01, 2.06]; p5.04), and 5.8 months.Median OS was 11.4 months (1.23 [0.80, 1.91]; p5.25), 10.5 months (1.50 [0.98, 2.30]; p5.06), and 16.3 months, respectively. ORR was 11.9{\%}, 5.9{\%}, and 10{\%}, respectively. Simtuzumab was tolerable in metastatic KRAS mutant CRC patients. Conclusion. The addition of simtuzumab to FOLFIRI did not improve clinical outcomes in patients with metastatic KRAS mutant CRC.",
author = "{Randolph Hecht}, J. and Benson, {Al B.} and Dmitry Vyushkov and Yingsi Yang and Johanna Bendell and Udit Verma",
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A phase II, randomized, double-blind, placebo-controlled study of simtuzumab in combination with FOLFIRI for the Second-Line treatment of metastatic KRAS mutant colorectal adenocarcinoma. / Randolph Hecht, J.; Benson, Al B.; Vyushkov, Dmitry; Yang, Yingsi; Bendell, Johanna; Verma, Udit.

In: Oncologist, Vol. 22, No. 3, 01.03.2017.

Research output: Contribution to journalArticle

TY - JOUR

T1 - A phase II, randomized, double-blind, placebo-controlled study of simtuzumab in combination with FOLFIRI for the Second-Line treatment of metastatic KRAS mutant colorectal adenocarcinoma

AU - Randolph Hecht, J.

AU - Benson, Al B.

AU - Vyushkov, Dmitry

AU - Yang, Yingsi

AU - Bendell, Johanna

AU - Verma, Udit

PY - 2017/3/1

Y1 - 2017/3/1

N2 - Background. Simtuzumab, a humanized IgG4 monoclonal antibody to lysyl oxidase-like 2 (LOXL2), blocks desmoplastic reaction in colorectal carcinoma (CRC) cells in vitro. Methods. Patients with metastatic Kirsten rat sarcoma viral oncogene homolog (KRAS) mutant CRC were randomized to receive second-line 5-fluorouracil, leucovorin, and irinotecan (FOLFIRI) with either 200 or 700 mg simtuzumab or placebo every 2 weeks in cycles of 28 days. Progression-free survival (PFS), overall survival (OS), objective response rate (ORR), and safety were assessed. Results. In total, 249 patients were randomized and treated with FOLFIRI/simtuzumab 700 mg (n584), FOLFIRI/simtuzumab 200 mg (n585), and FOLFIRI/placebo (n580). After a median follow-up of 5.1, 3.8, and 5.5 months, respectively, median PFS for each of the respective treatment groups was 5.5 months (adjusted HR [95% CI], p value versus placebo; 1.32 [0.92, 1.89]; p5.10), 5.4 months (1.45 [1.01, 2.06]; p5.04), and 5.8 months.Median OS was 11.4 months (1.23 [0.80, 1.91]; p5.25), 10.5 months (1.50 [0.98, 2.30]; p5.06), and 16.3 months, respectively. ORR was 11.9%, 5.9%, and 10%, respectively. Simtuzumab was tolerable in metastatic KRAS mutant CRC patients. Conclusion. The addition of simtuzumab to FOLFIRI did not improve clinical outcomes in patients with metastatic KRAS mutant CRC.

AB - Background. Simtuzumab, a humanized IgG4 monoclonal antibody to lysyl oxidase-like 2 (LOXL2), blocks desmoplastic reaction in colorectal carcinoma (CRC) cells in vitro. Methods. Patients with metastatic Kirsten rat sarcoma viral oncogene homolog (KRAS) mutant CRC were randomized to receive second-line 5-fluorouracil, leucovorin, and irinotecan (FOLFIRI) with either 200 or 700 mg simtuzumab or placebo every 2 weeks in cycles of 28 days. Progression-free survival (PFS), overall survival (OS), objective response rate (ORR), and safety were assessed. Results. In total, 249 patients were randomized and treated with FOLFIRI/simtuzumab 700 mg (n584), FOLFIRI/simtuzumab 200 mg (n585), and FOLFIRI/placebo (n580). After a median follow-up of 5.1, 3.8, and 5.5 months, respectively, median PFS for each of the respective treatment groups was 5.5 months (adjusted HR [95% CI], p value versus placebo; 1.32 [0.92, 1.89]; p5.10), 5.4 months (1.45 [1.01, 2.06]; p5.04), and 5.8 months.Median OS was 11.4 months (1.23 [0.80, 1.91]; p5.25), 10.5 months (1.50 [0.98, 2.30]; p5.06), and 16.3 months, respectively. ORR was 11.9%, 5.9%, and 10%, respectively. Simtuzumab was tolerable in metastatic KRAS mutant CRC patients. Conclusion. The addition of simtuzumab to FOLFIRI did not improve clinical outcomes in patients with metastatic KRAS mutant CRC.

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