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首页> 外文期刊>Journal of the advanced practitioner in oncology >Gastrointestinal Cancers: 2021 ASCO Annual Meeting Highlights for the Advanced Practitioner: The Advanced Practitioner Perspective:Trastuzumab Deruxtecan Shows Activity in Patients With Advanced HER2-Expressing Metastatic Colorectal Cancer, By JADPRO Staff
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Gastrointestinal Cancers: 2021 ASCO Annual Meeting Highlights for the Advanced Practitioner: The Advanced Practitioner Perspective:Trastuzumab Deruxtecan Shows Activity in Patients With Advanced HER2-Expressing Metastatic Colorectal Cancer, By JADPRO Staff

机译：Gastrointestinal Cancers: 2021 ASCO Annual Meeting Highlights for the Advanced Practitioner: The Advanced Practitioner Perspective:Trastuzumab Deruxtecan Shows Activity in Patients With Advanced HER2-Expressing Metastatic Colorectal Cancer, By JADPRO Staff

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Trastuzumab deruxtecan (Enhertu) demonstrated clinically meaningful activity and a manageable safety profile in patients with HER2-expressing unresectable and/or metastatic colorectal cancer who received at least two prior lines of standard treatment. Trastuzumab deruxtecan has already demonstrated clinical activity in four different cancer settings, and shows potential to improve patient outcomes in a number of HER2-targetable tumors. In the phase II DESTINY-CRC01 trial, patients had centrally confirmed HER2-expressing, RAS wild-type metastatic colorectal cancer that progressed after two or more prior regimens. 6.4 mg/kg of trastuzumab deruxtecan was administered every 3 weeks in three cohorts (A: HER2 IHC3+ or IHC2+/ISH+; B: IHC2+/ISH?; C: IHC1+). The primary endpoint was confirmed objective response rate (ORR) by independent central review in cohort A. Secondary endpoints were disease control rate (complete response + partial response + stable disease), duration of response (DOR), progression-free survival (PFS), and overall survival (OS). The Advanced Practitioner Perspective: Approximately 3% to 5% of colorectal cancers have amplification of the HER2 oncogene or overexpress its protein product, HER2. Accumulating data provide proof-of-principle support for the potential benefit of HER2-targeted therapies (e.g., trastuzumab plus pertuzumab or lapatinib, fam-trastuzumab deruxtecan) in these patients. At present, there are no approved HER2-targeted therapies for HER2-positive meta-static colorectal cancer. Recommended therapies based on guidelines include regorafenib or trifluridine/tipiracil as third line or later treatment with little effect on objective response. The DESTINY-CRC01 trial showed promising and durable activity in HER2-positive meta-static colorectal cancer refractory to standard treatment. Patients in this trial had regression of target lesions and lasting responses, resulting in PFS and OS benefits. In this trial, treatment-related adverse events needing monitoring include interstitial lung disease, which was managed with systemic corticosteroids. Recommendations include close monitoring of patients with symptoms such as fever, cough, and dyspnea. Treatment with trastuzumab deruxtecan should be interrupted in the setting of grade 1 interstitial lung disease and discontinued for grade 2, with further evaluation and consultation with pulmonary medicine. An evaluation should include bronchoscopy with broncho-alveolar lavage, pulse oximetry, and arterial blood gases. Pre-disposing factors, which could increase the likelihood of interstitial lung disease, should be identified. Given the promising results of this study, further research in a larger population of patients with HER2-positive metastatic colorectal cancer needs to be considered.

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