Response-guided neoadjuvant sacituzumab govitecan for localized triple negative breast cancer: results from the NeoSTAR trial
Mené sur 50 patientes atteintes d'un cancer du sein triple négatif de stade localisé (âge médian : 48,5 ans ; durée médiane de suivi : 18,9 mois), cet essai évalue l'efficacité, du point de vue du taux de réponse complète, et la toxicité d'un traitement néoadjuvant par sacituzumab govitécan (un conjugué anticorps-médicament ciblant Trop2) avec dose adaptée en fonction de la réponse thérapeutique
Background: Sacituzumab govitecan (SG), a novel antibody-drug conjugate targeting Trop2, is approved for pre-treated metastatic triple negative breast cancer (mTNBC). We conducted an investigator-initiated clinical trial evaluating neoadjuvant (NA) SG (NCT04230109), and report primary results Patients and Methods: Participants with early-stage TNBC received NA SG for 4 cycles. The primary objective was to assess pathological complete response (pCR) rate in breast and lymph nodes (ypT0/isN0) to SG. Secondary objectives included overall response rate (ORR), safety, event-free survival (EFS), and predictive biomarkers. A response-guided approach was utilized, and subsequent systemic therapy decisions were at the discretion of the treating physician. Results: From July 2020-August 2021, 50 participants were enrolled (median age = 48.5; 13 clinical stage I disease, 26 stage II, 11 stage III). Forty-nine (98%) completed 4 cycles of SG. Overall, the pCR rate with SG alone was 30% (n= 15, 95% CI 18%, 45%). The ORR per RECIST V1.1 after SG alone was 64% (n= 32/50, 95% CI 77%, 98%). Higher Ki-67 and tumor infiltrating lymphocytes (TILs) were predictive of pCR to SG (p = 0.007 for Ki-67; 0.002 for TILs), while baseline TROP2 expression was not (p = 0.440). Common AEs were nausea (82%), fatigue (76%), alopecia (76%), neutropenia (44%), and rash (48%). With a median follow-up time of 18.9 months (95% CI 16.3, 21.9), the 2-year EFS for all participants was 95%. Among participants with a pCR with SG (N = 15), the 2-year EFS was 100%. Conclusion: In the first NA trial with an ADC in localized TNBC, SG demonstrated single-agent efficacy and feasibility of response-guided escalation/de-escalation. Further research on optimal duration of SG as well as NA combination strategies, including immunotherapy, are needed.