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Trastuzumab Deruxtecan in PreviouslyTreated HER2-Positive Breast Cancer

Sénologie - Publié le 22/01/2020 par Ilfad Blazevic


BACKGROUND
Trastuzumab deruxtecan (DS-8201) is an antibody-drug conjugate composed of an
anti-HER2 (human epidermal growth factor receptor 2) antibody, a cleavable tetrapep-
tide-based linker, and a cytotoxic topoisomerase I inhibitor. In a phase 1 dose-finding
study, a majority of the patients with advanced HER2-positive breast cancer had a re-
sponse to trastuzumab deruxtecan (median response duration, 20.7 months). The ef-
ficacy of trastuzumab deruxtecan in patients with HER2-positive metastatic breast
cancer previously treated with trastuzumab emtansine requires confirmation.
METHODS
In this two-part, open-label, single-group, multicenter, phase 2 study, we evaluated
trastuzumab deruxtecan in adults with pathologically documented HER2-positive meta-
static breast cancer who had received previous treatment with trastuzumab emtansine.
In the first part of the study, we evaluated three different doses of trastuzumab derux-
tecan to establish a recommended dose; in the second part, we evaluated the efficacy
and safety of the recommended dose. The primary end point was the objective response,
according to independent central review. Key secondary end points were the disease-
control rate, clinical-benefit rate, duration of response and progression-free survival, and
safety.
RESULTS
Overall, 184 patients who had undergone a median of six previous treatments received
the recommended dose of trastuzumab deruxtecan (5.4 mg per kilogram of body weight).
In the intention-to-treat analysis, a response to therapy was reported in 112 patients
(60.9%; 95% confidence interval [CI], 53.4 to 68.0). The median duration of follow-up was
11.1 months (range, 0.7 to 19.9). The median response duration was 14.8 months (95%
CI, 13.8 to 16.9), and the median duration of progression-free survival was 16.4 months
(95% CI, 12.7 to not reached). During the study, the 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%). On independent adjudication, the trial drug was associ-
ated with interstitial lung disease 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 showed durable antitumor activity in a pretreated patient
population with HER2-positive metastatic breast cancer. In addition to nausea and
myelosuppression, interstitial lung disease was observed in a subgroup of patients and
requires attention to pulmonary symptoms and careful monitoring. (Funded by Daiichi
Sankyo and AstraZeneca; DESTINY-Breast01 ClinicalTrials.gov number, NCT03248492.)


Source : NEJM 2019