Datopotamab–deruxtecan in early-stage breast cancer: the sequential multiple assignment randomized I-SPY2.2 phase 2 trial
Menés respectivement sur 106 et 103 patientes atteintes d'un cancer du sein de stade précoce, ces deux essais de phase II évaluent l'efficacité, du point de vue du taux de réponse complète, et la toxicité du datopotamab déruxtécan avec ou sans durvalumab en traitement néoadjuvant, en fonction du statut tumoral HR et HER2
Résumé en anglais
Among the goals of patient-centric care are the advancement of effective personalized treatment, while minimizing toxicity. The phase 2 I-SPY2.2 trial uses a neoadjuvant sequential therapy approach in breast cancer to further these goals, testing promising new agents while optimizing individual outcomes. Here we tested datopotamab–deruxtecan (Dato-DXd) in the I-SPY2.2 trial for patients with high-risk stage 2/3 breast cancer. I-SPY2.2 uses a sequential multiple assignment randomization trial design that includes three sequential blocks of biologically targeted neoadjuvant treatment: the experimental agent(s) (block A), a taxane-based regimen tailored to the tumor subtype (block B) and doxorubicin–cyclophosphamide (block C). Patients are randomized into arms consisting of different investigational block A treatments. Algorithms based on magnetic resonance imaging and core biopsy guide treatment redirection after each block, including the option of early surgical resection in patients predicted to have a high likelihood of pathological complete response, the primary endpoint. There are two primary efficacy analyses: after block A and across all blocks for the six prespecified breast cancer subtypes (defined by clinical hormone receptor/human epidermal growth factor receptor 2 (HER2) status and/or the response-predictive subtypes). We report results of 103 patients treated with Dato-DXd. While Dato-DXd did not meet the prespecified threshold for success (graduation) after block A in any subtype, the treatment strategy across all blocks graduated in the hormone receptor-negative HER2−Immune−DNA repair deficiency− subtype with an estimated pathological complete response rate of 41%. No new toxicities were observed, with stomatitis and ocular events occurring at low grades. Dato-DXd was particularly active in the hormone receptor-negative/HER2−Immune−DNA repair deficiency− signature, warranting further investigation, and was safe in other subtypes in patients who followed the treatment strategy. ClinicalTrials.gov registration: NCT01042379.
