Phase II study of the dual EGFR/HER3 inhibitor duligotuzumab (MEHD7945A) vs. cetuximab in combination with FOLFIRI in RAS wild-type metastatic colorectal cancer

Andrew Graham Hill, Michael Findlay, Matthew Burge, Christopher Jackson, Pilar Garcia Alfonso, Leslie Samuel, Vinod Ganju, Meinolf Karthaus, Alessio Amatu, Mark Jeffrey, Maria Di Bartolomeo, John Bridgewater, Andrew Coveler, Manuel Hidalgo, Amy Kapp, Roxanna Sufan, Bruce McCall, William Hanley, Elicia Penuel, Andrea Pirzkall & 1 others Josep Tabernero

Research output: Contribution to journalArticle

7 Citations (Scopus)
4 Downloads (Pure)

Abstract

Purpose: Duligotuzumab is a dual-action antibody directed against EGFR and HER3. Experimental design: mCRC patients with KRAS ex2 wild-type received duligotuzumab or cetuximab and FOLFIRI until progression or intolerable toxicity. Mandatory tumor samples underwent mutation and biomarker analysis. Efficacy analysis was conducted in patients with RAS exon 2/3 wild-type tumors. Results: Of 134 randomized patients, 98 were RAS ex2/3 wild-type. Duligotuzumab provided no PFS or OR benefit compared to cetuximab; though there was a trend for lower ORR in the duligotuzumab arm. No relationship was seen between PFS or ORR and ERBB3, NRG1, or AREG expression. There were fewer skin rash events for duligotuzumab but more diarrhea. Although the incidence of grade ≥ 3 AEs was similar, the frequency of serious AEs was higher for duligotuzumab. Conclusions: Duligotuzumab plus FOLFIRI did not appear to improve the outcomes in patients with RAS exon 2/3 wild-type mCRC compared to cetuximab + FOLFIRI.
Original languageEnglish
Pages (from-to)2276-2284
Number of pages9
JournalClinical Cancer Research
Volume24
Issue number10
Early online date5 Mar 2018
DOIs
Publication statusPublished - May 2018

Fingerprint

Colorectal Neoplasms
Exons
Exanthema
Diarrhea
Neoplasms
Research Design
Biomarkers
Mutation
Cetuximab
MEHD7945A
Antibodies
Incidence

Cite this

Phase II study of the dual EGFR/HER3 inhibitor duligotuzumab (MEHD7945A) vs. cetuximab in combination with FOLFIRI in RAS wild-type metastatic colorectal cancer. / Hill, Andrew Graham; Findlay, Michael; Burge, Matthew; Jackson, Christopher; Garcia Alfonso, Pilar ; Samuel, Leslie; Ganju, Vinod; Karthaus, Meinolf; Amatu, Alessio; Jeffrey, Mark; Di Bartolomeo, Maria; Bridgewater, John; Coveler, Andrew; Hidalgo, Manuel; Kapp, Amy; Sufan, Roxanna; McCall, Bruce; Hanley, William; Penuel, Elicia; Pirzkall, Andrea; Tabernero, Josep.

In: Clinical Cancer Research, Vol. 24, No. 10, 05.2018, p. 2276-2284.

Research output: Contribution to journalArticle

Hill, AG, Findlay, M, Burge, M, Jackson, C, Garcia Alfonso, P, Samuel, L, Ganju, V, Karthaus, M, Amatu, A, Jeffrey, M, Di Bartolomeo, M, Bridgewater, J, Coveler, A, Hidalgo, M, Kapp, A, Sufan, R, McCall, B, Hanley, W, Penuel, E, Pirzkall, A & Tabernero, J 2018, 'Phase II study of the dual EGFR/HER3 inhibitor duligotuzumab (MEHD7945A) vs. cetuximab in combination with FOLFIRI in RAS wild-type metastatic colorectal cancer' Clinical Cancer Research, vol. 24, no. 10, pp. 2276-2284. https://doi.org/10.1158/1078-0432.CCR-17-0646
Hill, Andrew Graham ; Findlay, Michael ; Burge, Matthew ; Jackson, Christopher ; Garcia Alfonso, Pilar ; Samuel, Leslie ; Ganju, Vinod ; Karthaus, Meinolf ; Amatu, Alessio ; Jeffrey, Mark ; Di Bartolomeo, Maria ; Bridgewater, John ; Coveler, Andrew ; Hidalgo, Manuel ; Kapp, Amy ; Sufan, Roxanna ; McCall, Bruce ; Hanley, William ; Penuel, Elicia ; Pirzkall, Andrea ; Tabernero, Josep. / Phase II study of the dual EGFR/HER3 inhibitor duligotuzumab (MEHD7945A) vs. cetuximab in combination with FOLFIRI in RAS wild-type metastatic colorectal cancer. In: Clinical Cancer Research. 2018 ; Vol. 24, No. 10. pp. 2276-2284.
@article{15b13388860347bfb268776002d0dc06,
title = "Phase II study of the dual EGFR/HER3 inhibitor duligotuzumab (MEHD7945A) vs. cetuximab in combination with FOLFIRI in RAS wild-type metastatic colorectal cancer",
abstract = "Purpose: Duligotuzumab is a dual-action antibody directed against EGFR and HER3. Experimental design: mCRC patients with KRAS ex2 wild-type received duligotuzumab or cetuximab and FOLFIRI until progression or intolerable toxicity. Mandatory tumor samples underwent mutation and biomarker analysis. Efficacy analysis was conducted in patients with RAS exon 2/3 wild-type tumors. Results: Of 134 randomized patients, 98 were RAS ex2/3 wild-type. Duligotuzumab provided no PFS or OR benefit compared to cetuximab; though there was a trend for lower ORR in the duligotuzumab arm. No relationship was seen between PFS or ORR and ERBB3, NRG1, or AREG expression. There were fewer skin rash events for duligotuzumab but more diarrhea. Although the incidence of grade ≥ 3 AEs was similar, the frequency of serious AEs was higher for duligotuzumab. Conclusions: Duligotuzumab plus FOLFIRI did not appear to improve the outcomes in patients with RAS exon 2/3 wild-type mCRC compared to cetuximab + FOLFIRI.",
author = "Hill, {Andrew Graham} and Michael Findlay and Matthew Burge and Christopher Jackson and {Garcia Alfonso}, Pilar and Leslie Samuel and Vinod Ganju and Meinolf Karthaus and Alessio Amatu and Mark Jeffrey and {Di Bartolomeo}, Maria and John Bridgewater and Andrew Coveler and Manuel Hidalgo and Amy Kapp and Roxanna Sufan and Bruce McCall and William Hanley and Elicia Penuel and Andrea Pirzkall and Josep Tabernero",
note = "Acknowledgments The authors wish many thanks to all of the patients and the investigators who participated in this study. Writing assistance was provided by Genentech, Inc. This work was supported by Genentech, Inc. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.",
year = "2018",
month = "5",
doi = "10.1158/1078-0432.CCR-17-0646",
language = "English",
volume = "24",
pages = "2276--2284",
journal = "Clinical Cancer Research",
issn = "1078-0432",
publisher = "American Association for Cancer Research Inc.",
number = "10",

}

TY - JOUR

T1 - Phase II study of the dual EGFR/HER3 inhibitor duligotuzumab (MEHD7945A) vs. cetuximab in combination with FOLFIRI in RAS wild-type metastatic colorectal cancer

AU - Hill, Andrew Graham

AU - Findlay, Michael

AU - Burge, Matthew

AU - Jackson, Christopher

AU - Garcia Alfonso, Pilar

AU - Samuel, Leslie

AU - Ganju, Vinod

AU - Karthaus, Meinolf

AU - Amatu, Alessio

AU - Jeffrey, Mark

AU - Di Bartolomeo, Maria

AU - Bridgewater, John

AU - Coveler, Andrew

AU - Hidalgo, Manuel

AU - Kapp, Amy

AU - Sufan, Roxanna

AU - McCall, Bruce

AU - Hanley, William

AU - Penuel, Elicia

AU - Pirzkall, Andrea

AU - Tabernero, Josep

N1 - Acknowledgments The authors wish many thanks to all of the patients and the investigators who participated in this study. Writing assistance was provided by Genentech, Inc. This work was supported by Genentech, Inc. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

PY - 2018/5

Y1 - 2018/5

N2 - Purpose: Duligotuzumab is a dual-action antibody directed against EGFR and HER3. Experimental design: mCRC patients with KRAS ex2 wild-type received duligotuzumab or cetuximab and FOLFIRI until progression or intolerable toxicity. Mandatory tumor samples underwent mutation and biomarker analysis. Efficacy analysis was conducted in patients with RAS exon 2/3 wild-type tumors. Results: Of 134 randomized patients, 98 were RAS ex2/3 wild-type. Duligotuzumab provided no PFS or OR benefit compared to cetuximab; though there was a trend for lower ORR in the duligotuzumab arm. No relationship was seen between PFS or ORR and ERBB3, NRG1, or AREG expression. There were fewer skin rash events for duligotuzumab but more diarrhea. Although the incidence of grade ≥ 3 AEs was similar, the frequency of serious AEs was higher for duligotuzumab. Conclusions: Duligotuzumab plus FOLFIRI did not appear to improve the outcomes in patients with RAS exon 2/3 wild-type mCRC compared to cetuximab + FOLFIRI.

AB - Purpose: Duligotuzumab is a dual-action antibody directed against EGFR and HER3. Experimental design: mCRC patients with KRAS ex2 wild-type received duligotuzumab or cetuximab and FOLFIRI until progression or intolerable toxicity. Mandatory tumor samples underwent mutation and biomarker analysis. Efficacy analysis was conducted in patients with RAS exon 2/3 wild-type tumors. Results: Of 134 randomized patients, 98 were RAS ex2/3 wild-type. Duligotuzumab provided no PFS or OR benefit compared to cetuximab; though there was a trend for lower ORR in the duligotuzumab arm. No relationship was seen between PFS or ORR and ERBB3, NRG1, or AREG expression. There were fewer skin rash events for duligotuzumab but more diarrhea. Although the incidence of grade ≥ 3 AEs was similar, the frequency of serious AEs was higher for duligotuzumab. Conclusions: Duligotuzumab plus FOLFIRI did not appear to improve the outcomes in patients with RAS exon 2/3 wild-type mCRC compared to cetuximab + FOLFIRI.

U2 - 10.1158/1078-0432.CCR-17-0646

DO - 10.1158/1078-0432.CCR-17-0646

M3 - Article

VL - 24

SP - 2276

EP - 2284

JO - Clinical Cancer Research

JF - Clinical Cancer Research

SN - 1078-0432

IS - 10

ER -