Trastuzumab Plus Lapatinib Active in Refractory HER2+ Metastatic Colorectal Cancer
The combination of trastuzumab and the kinase inhibitor lapatinib is active and well tolerate in refractory HER2-positive metastatic colorectal cancer.
The combination of trastuzumab and the kinase inhibitor lapatinib is active and well tolerate in patients with refractory human epidermal growth factor 2 (HER2)-positive metastatic colorectal cancer, a study published in the journal The Lancet Oncology has shown.1
Because previous research in preclinical models demonstrated that dual HER2 blockade with trastuzumab and lapatinib resulted in inhibited tumor growth, researchers sought to evaluate the antitumor activity of the combination in patients with HER2-positive colorectal cancer.
For multicenter, open-label, proof-of-concept, phase 2 HERACLES trial, researchers in Italy enrolled 27 adult patients with KRAS exon 2 (codons 12 and 13) wild-type and HER2-positive metastatic colorectal cancer. All patients were refractory to standard of care treatment, including cetuximab or panitumumab.
Participants received trastuzumab 4 mg/kg intravenously as a loading dose, followed by 2 mg/kg once weekly, plus lapatinib 1000 mg orally daily until disease progression.
Results showed that at a median follow-up of 94 weeks, 30% (95% CI, 14 - 50) of the 27 patients achieved an objective response. Of those, 1 patient (4%; 95% CI, –3 to 11) achieved a complete response and 26% (95% CI, 9 - 43) had partial responses. Further, 12 patients (44%; 95% CI, 25 - 63) had stable disease.
In regard to safety, 22% of patients experienced grade 3 adverse events, including 4 cases of fatigue, 1 case of rash, and 1 case of elevated bilirubin concentration. No grade 4 or 5 adverse events or serious treatment-related adverse events were observed.
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Lapatinib and trastuzumab are both indicated for the treatment of HER2-overexpressing breast cancer, while trastuzumab is also approved for HER2-overexpressing metastatic gastric or gastroesophageal junction adenocarcinoma.
- Sartore-Bianchi A, Trusolino L, Martino C, et al. Dual-targeted therapy with trastuzumab and lapatinib in treatment-refractory, KRAS codon 12/13 wild-type, HER2-positive metastatic colorectal cancer (HERACLES): a proof-of-concept, multicentre, open-label, phase 2 trial [published online ahead of print April 20, 2016]. Lancet Oncol. doi: 10.1016/S1470-2045(16)00150-9.