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 -
