Dual inhibition of EGFR, HER3 confers no survival benefit in metastatic colorectal cancer
The dual-action antibody directed against epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 3 (HER3), duligotuzumab, does not appear to provide survival advantage compared with cetuximab in patients with RAS exon 2/3 wild-type metastatic colorectal cancer (mCRC) treated with the FOLFIRI (folinic acid, fluorouracil and irinotecan) regimen, according to the results of a phase II trial.
A total of 134 mCRC patients (median age 62 years; 61 percent male) with KRAS exon 2 wild-type were randomized to receive either duligotuzumab (n=68) or cetuximab (n=66) with FOLFIRI until progression or intolerable toxicity. Researchers performed mutation and biomarker analysis on mandatory tumour samples, as well as efficacy analysis in patients with RAS exon 2/3 wild-type tumours.
Of the patients, 98 had RAS exon 2/3 wild-type tumour, with 53 in the duligotuzumab arm and 45 in the cetuximab arm.
Efficacy data revealed that in the subgroup of patients with RAS wild-type tumours, duligotuzumab did not improve progression-free survival (median PFS, 7.3 vs 5.7 months; stratified hazard ratio [HR], 1.21; 90 percent CI, 0.81–1.81) or overall survival (median OS, 14.0 vs 13.1 months; stratified HR, 1.00; 0.61–1.66) compared with cetuximab. Moreover, a trend toward a lower objective response rate (ORR) was observed in the duligotuzumab arm (19 percent vs 33 percent; stratified HR, 0.47; 0.21–1.01).
There was no association observed between PFS or ORR and ERBB3, NRG1 or AREG expression. In terms of safety, duligotuzumab was associated with fewer skin rash events but more diarrhoea. Additionally, although the incidence of grade ≥3 adverse events (AEs) was similar between the two treatment arms, the frequency of serious AEs was higher with duligotuzumab.
Further development of duligotuzumab has been discontinued.