Background. Phase II study that included 184 patients with HER-2 positive metastatic breast cancer who previously were treated with trastuzumab emtansine to evaluate dosage safety and efficacy of Trastuzumab Deruxtecan. Median number of previous lines of therapy for metastatic disease was 6 (range 2 to 27) and included trastuzumab emtansine (100%), trastuzumab (100%), pertuzumab (65.8%), and other anti-HER2 therapies (54.3%)

Treatment Arm: Trastuzumab Deruxtecan 5.4 mg/kg body weight

Primary Endpoint: ORR
Median follow up: 11.1mo

ORR: 60.9%, 95%CI 53.4-68.0
Median response duration: 14.8mo 95% CI, 13.8-16.9
mPFS: 16.4 mo with 95% CI, 12.7 to not reached

Adverse events: Most common adverse events of grade 3 or higher were a decreased neutrophil count (in 20.7% of the patients), anemia (in 8.7%), and nausea (in 7.6%). Importantly, interstitial lung disease was seen in 13.6% of the patients (grade 1 or 2, 10.9%; grade 3 or 4, 0.5%; and grade 5, 2.2%).

Conclusions: Trastuzumab Deruxtecan has durable anti-tumor activity in pretreated HER-2 positive metastatic breast cancer patients with close monitoring of pulmonary function given risk of Interstitial lung disease.

Summarized by Pragnan Kancharla, MD

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Trastuzumab deruxtecan (Enhertu)
Mechanism:Targets HER-2 trastuzumab and a topoisomerase I inhibitor conjugate deruxtecan (a derivative of exatecan) very potent inhibitor of topo I, x10fold than SN38 (irinotecan).
Tox: cardiotoxicity>>↓LVEF, do baseline TTE, hold if EF<40% or drops >20%, myelosuppression, fatigue, infusion related reactions, pulmonary tox with cough, SOB, infiltrated similar >> ILD in ~9% of the patients.

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