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Response-guided neoadjuvant sacituzumab govitecan for localized triple negative breast cancer: results from the NeoSTAR trial

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.

 

Comments:

The results from the neoadjuvant clinical trial evaluating sacituzumab govitecan (SG) in early-stage triple-negative breast cancer (TNBC) are promising. Here's a breakdown:

**Patient Demographics:**
- 50 participants enrolled between July 2020 and August 2021.
- Median age of 48.5.
- Disease stages: 13 clinical stage I, 26 stage II, and 11 stage III.

**Treatment and Primary Results:**
- Participants received neoadjuvant SG for 4 cycles.
- Primary objective: Assess pathological complete response (pCR) rate in breast and lymph nodes (ypT0/isN0) to SG.
- 98% completed 4 cycles of SG.
- pCR rate with SG alone was 30% (n=15, 95% CI 18%, 45%).
- Overall response rate (ORR) per RECIST V1.1 after SG alone was 64% (n=32/50, 95% CI 77%, 98%).

**Predictive Biomarkers:**
- Higher Ki-67 and tumor infiltrating lymphocytes (TILs) were predictive of pCR to SG (p = 0.007 for Ki-67; 0.002 for TILs).
- Baseline TROP2 expression did not predict pCR (p = 0.440).

**Safety:**
- Common adverse events (AEs) included nausea (82%), fatigue (76%), alopecia (76%), neutropenia (44%), and rash (48%).

**Event-Free Survival (EFS):**
- Median follow-up time of 18.9 months.
- The 2-year EFS for all participants was 95%.
- Among participants achieving pCR with SG (N = 15), the 2-year EFS was 100%.

**Conclusion and Implications:**
- SG showed efficacy as a single agent in neoadjuvant treatment for localized TNBC.
- Response-guided escalation/de-escalation in subsequent systemic therapy decisions was feasible.
- Further research is needed on the optimal duration of SG and neoadjuvant combination strategies, including immunotherapy.

The study indicates significant efficacy in achieving a pathological complete response with SG in early-stage TNBC, along with a manageable safety profile. Additionally, it highlights the importance of Ki-67 and TILs as predictive biomarkers. Further investigations are warranted to optimize SG's duration and explore potential combination therapies to enhance its effectiveness.

Related Products

Cat.No. Product Name Information
E2841 Sacituzumab-govitecan Sacituzumab govitecan (IMMU-132) is an antibody-drug conjugate (ADC) targeting Trop-2 for delivery of SN-38, showing anticancer activity. Sacituzumab govitecan has a molecular weight of 160KDa. This product is supplied as 10mg/ml PBS solution.This product is discontinued. We recommend the replacement products: D4002.

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